Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02938520




Registration number
NCT02938520
Ethics application status
Date submitted
15/09/2016
Date registered
19/10/2016
Date last updated
31/08/2023

Titles & IDs
Public title
Study to Evaluate the Efficacy, Safety, and Tolerability of Long-acting Intramuscular Cabotegravir and Rilpivirine for Maintenance of Virologic Suppression Following Switch From an Integrase Inhibitor in HIV-1 Infected Therapy Naive Participants
Scientific title
A Phase III, Randomized, Multicenter, Parallel-group, Open-Label Study Evaluating the Efficacy, Safety, and Tolerability of Long-Acting Intramuscular Cabotegravir and Rilpivirine for Maintenance of Virologic Suppression Following Switch From an Integrase Inhibitor Single Tablet Regimen in HIV-1 Infected Antiretroviral Therapy Naive Adult Participants
Secondary ID [1] 0 0
2016-001646-25
Secondary ID [2] 0 0
201584
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cabotegravir (CAB) tablet
Treatment: Drugs - Rilpivirine (RPV) tablet
Treatment: Drugs - Cabotegravir - Injectable Suspension (CAB LA)
Treatment: Drugs - Rilpivirine - Injectable Suspension (RPV LA)
Treatment: Drugs - ABC/DTG/3TC STR - Tablet
Treatment: Drugs - DTG Tablet

Experimental: CAB LA + RPV LA every 4 weeks - After Induction Phase with ABC/DTG/3TC (or DTG + two NRTIs), eligible participants will receive oral CAB 30 mg + RPV 25 mg once daily for approximately four weeks. At visit Week 4b subjects will receive an initial loading dose of CAB LA (600 mg) and RPV LA (900 mg) at Week 4b. From Week 8 onwards, subjects will receive CAB LA (400 mg) + RPV LA (600 mg) injections every 4 weeks.

Active Comparator: ABC / DTG / 3TC (600 mg/50mg/300mg) once daily - After the Induction Phase with ABC/DTG/3TC (or DTG + two NRTIs), eligible participants will continue to receive oral ABC/DTG/3TC (or DTG + two NRTIs) initiated during the Induction Phase for 100 weeks. At the end of the Maintenance Phase, eligible participants receiving ABC/DTG/3TC (or DTG + two NRTIs) have the option to continue in the study by switching to CAB LA + RPV LA in the Extension Phase. These participants will transition to LA dosing at either Week 100 (direct to inject) or Week 104b (if using optional oral lead-in with CAB 30 mg + RPV 25 mg once daily).


Treatment: Drugs: Cabotegravir (CAB) tablet
It is a white oval shaped film coated 30 mg tablets for oral administration. CAB Tablet is composed of cabotegravir sodium, lactose monohydrate, microcrystalline cellulose, hypromellose, sodium starch glycolate, magnesium stearate, and white film-coat.

Treatment: Drugs: Rilpivirine (RPV) tablet
It is a 25 mg tablet with off-white, round, biconvex, film-coated and debossed on one side with "TMC" and the other side with "25". Each tablet contains RPV hydrochloride, and the inactive ingredients croscarmellose sodium, lactose monohydrate, magnesium stearate, polysorbate 20, povidone K30 and silicified microcrystalline cellulose.

Treatment: Drugs: Cabotegravir - Injectable Suspension (CAB LA)
It is a sterile white to slightly pink suspension containing 200 mg/mL of CAB as free acid for administration by intramuscular (IM) injection. Each vial is for single-dose use containing a withdrawable volume of 2.0 mL, and does not require dilution prior to administration. CAB LA is composed of cabotegravir free acid, polysorbate 20, polyethylene glycol 3350, mannitol, and water for injection.

Treatment: Drugs: Rilpivirine - Injectable Suspension (RPV LA)
It is a sterile white suspension containing 300 mg/mL of RPV as the free base. The route of administration is by intramuscular (IM) injection. Each vial contains a nominal fill of 2.0 mL, and does not require dilution prior to administration. RPV LA requires refrigeration and must be protected from light. RPV LA is composed of RPV free base, poloxamer 338, sodium dihydrogen phosphate monohydrate, citric acid monohydrate, glucose monohydrate, sodium hydroxide, water for injection.

Treatment: Drugs: ABC/DTG/3TC STR - Tablet
It is a purple, biconvex, oval, tablet debossed with "572 Tri" on one side, film-coated tablet contains abacavir sulphate equivalent to 600 mg of abacavir, dolutegravir sodium equivalent to 50 mg dolutegravir, and 300 mg of lamivudine. The inactive ABC/DTG/3TC tablet ingredients include D-mannitol, magnesium stearate, microcrystalline cellulose, povidone, and sodium starch glycolate.

Treatment: Drugs: DTG Tablet
It is a yellow, round, biconvex, 50 mg film-coated tablet debossed with "SV 572" on one side and "50" on the other side. Each tablet of DTG also contains the following inactive ingredients: D-mannitol, microcrystalline cellulose, povidone K29/32, sodium starch glycolate, and sodium stearyl fumarate.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Virologic Failure (HIV-1 Ribonucleic Acid [RNA] >=50 Copies Per Millilter [mL]) Using Snapshot Algorithm at Week 48
Timepoint [1] 0 0
Week 48
Secondary outcome [1] 0 0
Percentage of Participants With HIV-1 RNA <50 Copies/mL Using Snapshot Algorithm at Week 48
Timepoint [1] 0 0
Week 48
Secondary outcome [2] 0 0
Number of Participants With HIV-1 RNA <200 Copies/mL Using Snapshot Algorithm at Week 48
Timepoint [2] 0 0
Week 48
Secondary outcome [3] 0 0
Number of Participants With Confirmed Virologic Failure (CVF) During the Maintenance Phase
Timepoint [3] 0 0
Week 48
Secondary outcome [4] 0 0
Absolute Values for Plasma HIV-1 RNA at Week 48
Timepoint [4] 0 0
Week 48
Secondary outcome [5] 0 0
Change From Baseline Values for Plasma HIV-1 RNA at Week 48
Timepoint [5] 0 0
Baseline (Day 1) and at Week 48
Secondary outcome [6] 0 0
Absolute Values for CD4+ Lymphocyte Count at Week 48
Timepoint [6] 0 0
Week 48
Secondary outcome [7] 0 0
Change From Baseline Values for CD4+ Lymphocyte Count at Week 48
Timepoint [7] 0 0
Baseline (Day 1) and Week 48
Secondary outcome [8] 0 0
Number of Participants With Disease Progression
Timepoint [8] 0 0
Day 1 up to an average of 59 weeks
Secondary outcome [9] 0 0
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
Timepoint [9] 0 0
Day 1 up to an average of 59 Weeks
Secondary outcome [10] 0 0
Number of Participants With Severity of Adverse Events
Timepoint [10] 0 0
Up to Week 48
Secondary outcome [11] 0 0
Absolute Values for Hematology Parameters Over Time Including Week 48: Basophils, Eosinophils, Leukocytes, Lymphocytes, Neutrophils, Monocytes, and Platelets
Timepoint [11] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [12] 0 0
Absolute Values for Hematology Parameters Over Time Including Week 48: Erythrocyte Mean Corpuscular Volume
Timepoint [12] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [13] 0 0
Absolute Values for Hematology Parameters Over Time Including Week 48: Erythrocytes
Timepoint [13] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [14] 0 0
Absolute Values for Hematology Parameters Over Time Including Week 48: Hemoglobin
Timepoint [14] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [15] 0 0
Absolute Values for Hematology Parameters Over Time Including Week 48: Hematocrit
Timepoint [15] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [16] 0 0
Absolute Values for Clinical Chemistry Parameters Over Time Including Week 48: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatinine Kinase (CK)
Timepoint [16] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [17] 0 0
Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Albumin
Timepoint [17] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [18] 0 0
Absolute Values for Clinical Chemistry Parameters Over Time Including Week 48: Bilirubin, Direct Bilirubin and Creatinine
Timepoint [18] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [19] 0 0
Absolute Values for Clinical Chemistry Parameters: Total Carbon-dioxide (CO2), Chloride, Glucose, Phosphate, Potassium, Sodium and Urea Over Time Including Week 48
Timepoint [19] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [20] 0 0
Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Lipase
Timepoint [20] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [21] 0 0
Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Creatinine Clearance.
Timepoint [21] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [22] 0 0
Absolute Values for Fasting Lipid Panel Overtime Including Week 48
Timepoint [22] 0 0
Baseline (Day 1) and at Week 48
Secondary outcome [23] 0 0
Number of Participants With Abnormal Urinalysis Parameter Over Time Including Week 48
Timepoint [23] 0 0
Baseline (Day 1) and at Weeks 4, 24 and 48
Secondary outcome [24] 0 0
Number of Participants With Urine Potential of Hydrogen (pH) Over Time Including Week 48
Timepoint [24] 0 0
Baseline (Day 1) and at Weeks 4, 24 and 48
Secondary outcome [25] 0 0
Change From Baseline for Hematology Parameters: Basophil, Eosinophils, Leukocytes, Lymphocytes, Neutrophils, Monocytes, and Platelets
Timepoint [25] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [26] 0 0
Change From Baseline for Hematology Parameters: Erythrocyte Mean Corpuscular Volume
Timepoint [26] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [27] 0 0
Change From Baseline for Hematology Parameters: Erythrocytes
Timepoint [27] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [28] 0 0
Change From Baseline for Hematology Parameters: Hematocrit
Timepoint [28] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [29] 0 0
Change From Baseline for Hematology Parameters: Hemoglobin
Timepoint [29] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [30] 0 0
Change From Baseline in Clinical Chemistry Parameters Over Time Including Week 48: ALT, ALP, AST and CK
Timepoint [30] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [31] 0 0
Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Albumin
Timepoint [31] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [32] 0 0
Change From Baseline Values for Clinical Chemistry Parameters Over Time Including Week 48: Bilirubin, Direct Bilirubin and Creatinine
Timepoint [32] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [33] 0 0
Change From Baseline Values for Clinical Chemistry Parameters Over Time Including Week 48
Timepoint [33] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [34] 0 0
Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Lipase
Timepoint [34] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [35] 0 0
Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Creatinine Clearance
Timepoint [35] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [36] 0 0
Change From Baseline Values for Fasting Lipid Panel and Glucose Overtime Including Week 48
Timepoint [36] 0 0
Baseline (Day 1) and at Week 48
Secondary outcome [37] 0 0
Change From Baseline Values in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio Over Time Including Week 48
Timepoint [37] 0 0
Baseline (Day 1) and at Weeks 4, 24 and 48
Secondary outcome [38] 0 0
Change From Baseline Values in Urine Creatinine Over Time Including Week 48
Timepoint [38] 0 0
Baseline (Day 1) and at Weeks 4, 24 and 48
Secondary outcome [39] 0 0
Change From Baseline Values in Urine Phosphate Over Time Including Week 48
Timepoint [39] 0 0
Baseline (Day 1) and at Weeks 4, 24 and 48
Secondary outcome [40] 0 0
Change From Baseline Values in Urine Retinol Binding Protein Over Time Including Week 48
Timepoint [40] 0 0
Baseline (Day 1) and at Week 48
Secondary outcome [41] 0 0
Change From Baseline Values in Urine Specific Gravity Over Time Including Week 48
Timepoint [41] 0 0
Baseline (Day 1) and at Weeks 4, 24 and 48
Secondary outcome [42] 0 0
Change From Baseline Values in Urine pH Over Time Including Week 48
Timepoint [42] 0 0
Baseline (Day 1) and at Weeks 4, 24 and 48
Secondary outcome [43] 0 0
Number of Participants Who Discontinued or Withdrawn Due to AEs Over Time Including Week 48
Timepoint [43] 0 0
Up to Week 48
Secondary outcome [44] 0 0
Percentage Change From Baseline in Fasting Lipids Overtime Including Week 48
Timepoint [44] 0 0
Baseline (Day 1) and at Week 48
Secondary outcome [45] 0 0
Number of Participants With Phenotypic Resistance Through Week 48
Timepoint [45] 0 0
Week 48
Secondary outcome [46] 0 0
Number of Participants With Genotypic Resistance Through Week 48
Timepoint [46] 0 0
Week 48
Secondary outcome [47] 0 0
Area Under the Curve (AUC) for CAB LA
Timepoint [47] 0 0
Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48; 1 Week post-dose at Weeks 5, 41, 2 hours post-dose at Weeks 4 and 48
Secondary outcome [48] 0 0
AUC for RPV LA
Timepoint [48] 0 0
Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48; 1 Week post-dose at Weeks 5, 41, 2 hours post-dose at Weeks 4 and 48
Secondary outcome [49] 0 0
Plasma Trough Concentration (Ctrough) for CAB LA Evaluable
Timepoint [49] 0 0
Pre-dose at Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [50] 0 0
Ctrough for RPV LA Evaluable
Timepoint [50] 0 0
Pre-dose at Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [51] 0 0
Maximum Concentration (Cmax) in Plasma for CAB LA Evaluable at Week 41
Timepoint [51] 0 0
Week 41- 1 Week post dose
Secondary outcome [52] 0 0
Cmax in Plasma for RPV LA Evaluable at Week 41
Timepoint [52] 0 0
Week 41- 1 Week post dose
Secondary outcome [53] 0 0
Change From Week 5 in Dimension Scores Using Perception of Injection Questionnaire (PIN)-Last Observation Carried Forward (LOCF)
Timepoint [53] 0 0
Weeks 5 and at Weeks 41 and 48
Secondary outcome [54] 0 0
Percentage of Participants With Extremely or Very Acceptable Pain and Local Reaction: Acceptability Score on PIN Questionnaire
Timepoint [54] 0 0
Weeks 5, 41 and 48
Secondary outcome [55] 0 0
Change From Baseline in Life Satisfaction (LISAT) Using HIV/AIDs-targeted Quality of Life (HATQoL) Questionnaire
Timepoint [55] 0 0
Baseline (Day 1) and at Weeks 24 and 48
Secondary outcome [56] 0 0
Change From Baseline in HIV Medication, MEDWO Using HATQoL
Timepoint [56] 0 0
Baseline and at Weeks 24 and 48
Secondary outcome [57] 0 0
Change From Baseline in DISWO Using HATQoL
Timepoint [57] 0 0
Baseline and at Weeks 24 and 48
Secondary outcome [58] 0 0
Change From Baseline in Health Status Using 12-item Short Form Survey (SF-12)
Timepoint [58] 0 0
Baseline and at Weeks 24 and 48
Secondary outcome [59] 0 0
Change From Baseline in Total Treatment Satisfaction Using HIV Treatment Satisfaction Questionnaire (HIVTSQs) at Weeks 4b, 24 and 44
Timepoint [59] 0 0
Baseline and at Weeks 4b, 24 and 44
Secondary outcome [60] 0 0
Change in Treatment Satisfaction Over Time Using HIVTSQc at Week 48
Timepoint [60] 0 0
Week 48
Secondary outcome [61] 0 0
Change From Baseline in Individual Item Scores of HIVTSQs at Weeks 4b, 24 and 44
Timepoint [61] 0 0
Baseline and at Weeks 4b, 24 and 44
Secondary outcome [62] 0 0
Change From Baseline in Treatment Acceptance at Weeks 8, 24 and 48 Using "General Acceptance" Dimension of the Chronic Treatment Acceptance (ACCEPT) Questionnaire
Timepoint [62] 0 0
Baseline and at Weeks 8, 24 and 48
Secondary outcome [63] 0 0
Change From 4b in Tolerability of Injection at Weeks 5, 40 and 41 Using Numeric Rating Scale (NRS) Within CAB LA+RPV LA Arm
Timepoint [63] 0 0
Weeks 4b, 5, 40 and 41

Eligibility
Key inclusion criteria
- HIV-1 infected, ART-naive men or women aged 18 years or greater at
the time of signing the informed consent. - HIV-1 infection as documented by Screening
plasma HIV-1 RNA >=1000 c/mL; - Antiretroviral-naive (<=10 days of prior therapy with any
antiretroviral agent following a diagnosis of HIV-1 infection). Any previous exposure to an
HIV integrase inhibitor or non-nucleoside reverse transcriptase inhibitor will be
exclusionary. - Female Participants: A female participant is eligible to participate if she
is not pregnant at Screening and first day of Induction Phase (as confirmed by a negative
serum human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the
following conditions applies: Non-reproductive potential defined as: Pre-menopausal females
with one of the following: Documented tubal ligation; Documented hysteroscopic tubal
occlusion procedure with follow-up confirmation of bilateral tubal occlusion; Hysterectomy;
Documented Bilateral Oophorectomy; Postmenopausal defined as 12 months of spontaneous
amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating
hormone (FSH) and estradiol levels consistent with menopause. Females on hormone
replacement therapy (HRT) and whose menopausal status is in doubt will be required to use
one of the highly effective contraception methods if they wish to continue their HRT during
the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal
status prior to study enrolment. Reproductive potential and agrees to follow one of the
options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in
Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study
medication, throughout the study, and for at least 30 days after discontinuation of all
oral study medications and for at least 52 weeks after discontinuation of CAB LA and RPV
LA. The investigator is responsible for ensuring that participants understand how to
properly use these methods of contraception. All participants in the study should be
counseled on safer sexual practices including the use and benefit/risk of effective barrier
methods (e.g., male condom) and on the risk of HIV transmission to an uninfected partner. -
Capable of giving signed informed consent which includes compliance with the requirements
and restrictions listed in the consent form and in this protocol. - In France, a
participant will be eligible for inclusion in this study only if either affiliated to or a
beneficiary of a social security category.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Women who are pregnant, breastfeeding, or plan to become pregnant or
breastfeed during the study. - Any evidence at Screening of an active Centers for Disease
and Prevention Control (CDC) Stage 3 disease, except cutaneous Kaposi's sarcoma not
requiring systemic therapy or historic or current cluster of differentiation4+ (CD4+) cell
count <200 cells/ cubic millimeter (mm^3) are not exclusionary. - Participants with known
moderate to severe hepatic impairment. - Any pre-existing physical or mental condition
(including substance abuse disorder) which, in the opinion of the Investigator, may
interfere with the participant's ability to comply with the dosing schedule and/or protocol
evaluations or which may compromise the safety of the participant. - Participants
determined by the Investigator to have a high risk of seizures, including participants with
an unstable or poorly controlled seizure disorder. A participant with a prior history of
seizure may be considered for enrolment if the Investigator believes the risk of seizure
recurrence is low. All cases of prior seizure history should be discussed with the Medical
Monitor prior to enrolment. - Participant who, in the investigator's judgment, poses a
significant suicide risk. Participant's recent history of suicidal behavior and/or suicidal
ideation should be considered when evaluating for suicide risk. - The participant has a
tattoo or other dermatological condition overlying the gluteus region which may interfere
with interpretation of injection site reactions. - Evidence of Hepatitis B virus (HBV)
infection based on the results of testing at Screening for Hepatitis B surface antigen
(HBsAg), Hepatitis B core antibody (anti HBc), Hepatitis B surface antibody (anti-HBs) and
HBV dioxyribose nucleic acid (DNA) as follows: Participants positive for HBsAg are
excluded; Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg
status) and positive for HBV DNA are excluded. Note: Participants positive for anti-HBc
(negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune
to HBV and are not excluded. - Asymptomatic individuals with chronic hepatitis C virus
(HCV) infection will not be excluded, however Investigators must carefully assess if
therapy specific for HCV infection is required; participants who are anticipated to require
HCV treatment prior to Week 48 of the Maintenance Phase must be excluded. HCV treatment on
study may be permitted post Week 48, following consultation with the Medical Monitor.
Participants with HCV co-infection will be allowed entry into Phase 3 studies if: Liver
enzymes meet entry criteria; HCV Disease has undergone appropriate work-up, HCV is not
advanced, and will not require treatment prior to the Week 48 visit. Additional information
(where available) on participants with HCV co-infection at screening should include results
from any liver biopsy, fibroscan, ultrasound, or other fibrosis evaluation, history of
cirrhosis or other decompensated liver disease, prior treatment, and timing/plan for HCV
treatment. In the event that recent biopsy or imaging data is not available or is
inconclusive, the Fib-4 score will be used to verify eligibility. A Fib-4 score > 3.25 is
exclusionary; Fib-4 scores 1.45 - 3.25 requires Medical Monitor consultation. Fibrosis 4
Score Formula: (Age x AST)/(Platelets x [square root of ALT]). - Unstable liver disease (as
defined by any of the following: presence of ascites, encephalopathy, coagulopathy,
hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary
abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or
otherwise stable chronic liver disease per investigator assessment). - History of liver
cirrhosis with or without hepatitis viral co-infection. - Ongoing or clinically relevant
pancreatitis. - All participants will be screened for syphilis (rapid plasma reagin [RPR]).
Participants with untreated syphilis infection, defined as a positive RPR without clear
documentation of treatment, are excluded. Participants with a positive RPR test who have
not been treated may be rescreened at least 30 days after completion of antibiotic
treatment for syphilis. - Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal
cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical,
anal or penile intraepithelial neoplasia; other localized malignancies require agreement
between the investigator and the study Medical Monitor for inclusion of the participant
prior to enrollment. - Any condition which, in the opinion of the Investigator, may
interfere with the absorption, distribution, metabolism or excretion of the drug or render
the participant unable to receive study medication. - History or presence of allergy or
intolerance to the study drugs or their components or drugs of their class. In addition, if
heparin is used during pharmacokinetic sampling (PK) sampling, participants with a history
of sensitivity to heparin or heparin-induced thrombocytopenia must not be enrolled. -
Current or anticipated need for chronic anti-coagulation. - Alanine aminotransferase (ALT)
>=3 times upper limit normal (ULN). - Clinically significant cardiovascular disease, as
defined by history/evidence of congestive heart failure, symptomatic arrhythmia,
angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous
transluminal coronary angioplasty (PTCA) or any clinically significant cardiac disease. -
Exposure to an experimental drug and/or experimental vaccine within 28 days or 5 half-lives
of the test agent, or twice the duration of the biological effect of the test agent,
whichever is longer, prior to the first dose of investigational product (IP). - Treatment
with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic
chemotherapeutic agents; tuberculosis (TB) therapy, with the exception of treatment of
latent TB with isoniazid; Immunomodulators that alter immune responses (such as chronic
systemic corticosteroids, interleukins, or interferons). Note: Participants using
short-term (e.g. =<21 day) systemic corticosteroid treatment, topical, inhaled or
intranasal corticosteroids are eligible for enrollment. - Treatment with an HIV-1
immunotherapeutic vaccine within 90 days of Screening. - Treatment with any agent, except
recognized ART as allowed above, with documented activity against HIV-1 within 28 days of
the first dose of IP. - Use of medications which are associated with Torsades de Pointes -
Any evidence of primary resistance to non-nuclease reverse transcriptase inhibitors
(NNRTIs) (except for K103N which is allowed), or any known resistance to INIs from
historical resistance test results. Note: re-tests of Screening genotypes are allowed only
at the discretion of the study virologist. - Participants who are HLA-B*5701 positive and
are unable to use an nuclease reverse transcriptase inhibitors (NRTI) backbone that does
not contain abacavir (participants who are HLA-B*5701 positive may be enrolled if they use
a NRTI backbone that does not contain abacavir; HLA-B*5701 positive participants may be
excluded from the study if local provision of an alternate NRTI backbone is not possible).
- Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the
Screening Phase to verify a result. - Any acute laboratory abnormality at Screening, which,
in the opinion of the Investigator, would preclude the participant's participation in the
study of an investigational compound. - Participant has estimated creatinine clearance <50
mL/min/1.73m^2 via the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
equation. - Participants who are currently participating in or anticipate to be selected
for any other interventional study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/10/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2026
Actual
Sample size
Target
Accrual to date
Final
631
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Nebraska
Country [10] 0 0
United States of America
State/province [10] 0 0
New Jersey
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
Rhode Island
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
Canada
State/province [15] 0 0
British Columbia
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
France
State/province [18] 0 0
Bobigny
Country [19] 0 0
France
State/province [19] 0 0
Lyon Cedex 03
Country [20] 0 0
France
State/province [20] 0 0
Marseille.
Country [21] 0 0
France
State/province [21] 0 0
Paris Cedex 10
Country [22] 0 0
France
State/province [22] 0 0
Paris Cedex 12
Country [23] 0 0
France
State/province [23] 0 0
Paris Cedex 13
Country [24] 0 0
France
State/province [24] 0 0
Paris Cedex 20
Country [25] 0 0
France
State/province [25] 0 0
Paris
Country [26] 0 0
Germany
State/province [26] 0 0
Bayern
Country [27] 0 0
Germany
State/province [27] 0 0
Hessen
Country [28] 0 0
Germany
State/province [28] 0 0
Niedersachsen
Country [29] 0 0
Germany
State/province [29] 0 0
Nordrhein-Westfalen
Country [30] 0 0
Germany
State/province [30] 0 0
Berlin
Country [31] 0 0
Germany
State/province [31] 0 0
Hamburg
Country [32] 0 0
Germany
State/province [32] 0 0
München
Country [33] 0 0
Italy
State/province [33] 0 0
Lazio
Country [34] 0 0
Italy
State/province [34] 0 0
Lombardia
Country [35] 0 0
Japan
State/province [35] 0 0
Aichi
Country [36] 0 0
Japan
State/province [36] 0 0
Osaka
Country [37] 0 0
Japan
State/province [37] 0 0
Tokyo
Country [38] 0 0
Netherlands
State/province [38] 0 0
Amsterdam
Country [39] 0 0
Netherlands
State/province [39] 0 0
Groningen
Country [40] 0 0
Netherlands
State/province [40] 0 0
Rotterdam
Country [41] 0 0
Netherlands
State/province [41] 0 0
Utrecht
Country [42] 0 0
Russian Federation
State/province [42] 0 0
Ekaterinburg
Country [43] 0 0
Russian Federation
State/province [43] 0 0
Kazan
Country [44] 0 0
Russian Federation
State/province [44] 0 0
Kemerovo
Country [45] 0 0
Russian Federation
State/province [45] 0 0
Krasnodar
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Lipetsk
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Moscow
Country [48] 0 0
Russian Federation
State/province [48] 0 0
Orel
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Saint-Petersburg
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Saratov
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Smolensk
Country [52] 0 0
Russian Federation
State/province [52] 0 0
St. Petersburg
Country [53] 0 0
Russian Federation
State/province [53] 0 0
Toliyatti
Country [54] 0 0
South Africa
State/province [54] 0 0
Free State
Country [55] 0 0
South Africa
State/province [55] 0 0
Gauteng
Country [56] 0 0
South Africa
State/province [56] 0 0
KwaZulu- Natal
Country [57] 0 0
South Africa
State/province [57] 0 0
Mpumalanga
Country [58] 0 0
South Africa
State/province [58] 0 0
Durban
Country [59] 0 0
South Africa
State/province [59] 0 0
Observatory, Cape Town
Country [60] 0 0
Spain
State/province [60] 0 0
Barcelona
Country [61] 0 0
Spain
State/province [61] 0 0
Bilbao
Country [62] 0 0
Spain
State/province [62] 0 0
Elche (Alicante)
Country [63] 0 0
Spain
State/province [63] 0 0
Ferrol ( A Coruña)
Country [64] 0 0
Spain
State/province [64] 0 0
Granada
Country [65] 0 0
Spain
State/province [65] 0 0
La Coruña
Country [66] 0 0
Spain
State/province [66] 0 0
La Laguna-Tenerife
Country [67] 0 0
Spain
State/province [67] 0 0
Madrid
Country [68] 0 0
Spain
State/province [68] 0 0
Murcia
Country [69] 0 0
Spain
State/province [69] 0 0
Palma de Mallorca
Country [70] 0 0
Spain
State/province [70] 0 0
Pama de Mallorca
Country [71] 0 0
Spain
State/province [71] 0 0
San Sebastian de los Reyes
Country [72] 0 0
Spain
State/province [72] 0 0
Santa Cruz de Tenerife
Country [73] 0 0
Spain
State/province [73] 0 0
Santander
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Birmingham
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Coventry
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Leeds
Country [77] 0 0
United Kingdom
State/province [77] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ViiV Healthcare
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Janssen Pharmaceuticals
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
GlaxoSmithKline
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The First Long-Acting Injectable Regimen (FLAIR) study is being conducted to establish if
human immunodeficiency virus type-1 (HIV-1) infected adult participants whose virus is
virologically suppressed on an integrase inhibitor single tablet regimen (INI STR) will
remain suppressed after switching to a two-drug intramuscular (IM) long-acting (LA) regimen
of cabotegravir (CAB) and rilpivirine (RPV). In this study, the INI STR will be limited to
abacavir/dolutegravir/lamivudine (ABC/DTG/3TC). FLAIR is a Phase 3, multi-phase, randomized,
open label, active-controlled, multicenter, parallel-group, non-inferiority study in HIV-1,
anti-retroviral therapy (ART)-naïve adult participants. This study is designed to demonstrate
the non-inferior antiviral activity of switching to a two drug CAB LA 400 mg + RPV LA 600 mg
regimen every 4 weeks (Q4W: monthly) compared to remaining on ABC/DTG/3TC over 48 weeks (4
weeks oral CAB + RPV, 44 weeks LA therapy). Participants who are HLA-B*5701 positive at
Screening may enroll into the study and receive DTG plus a non-abacavir containing dual
nucleoside reverse transcriptase inhibitor (NRTI) regimen. Eligible participants will enroll
into the Induction Phase of the study and receive ABC/DTG/3TC for 20 weeks (Week [-20] to Day
1). Participants who have an HIV 1 ribose nucleic acid (RNA) <50 copies per milliliter (c/mL)
at Week (-4) will be randomized (1:1) into the Maintenance Phase at Day 1 to either continue
ABC/DTG/3TC or to discontinue ABC/DTG/3TC and begin oral therapy with CAB 30 mg + RPV 25 mg
once daily for approximately 4 Weeks, followed by monthly CAB LA + RPV LA injections from
visit Week 4b until study completion or withdrawal. Participants who successfully complete
Week 100 (without meeting study defined withdrawal criteria and who remain virologically
suppressed through Week 96: HIV-1 RNA <50 c/mL) will be given the option to switch to the LA
arm in the Extension Phase (using an optional oral lead-in with CAB + RPV) or be withdrawn
from the study. Participants will continue to receive injections every 4 weeks during the
Extension Phase until CAB LA and RPV LA are either locally approved and commercially
available, the participant no longer derives clinical benefit, the participant meets a
protocol-defined reason for discontinuation, or until development of either CAB LA or RPV LA
is terminated.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02938520
Trial related presentations / publications
Orkin C, Arasteh K, Gorgolas Hernandez-Mora M, Pokrovsky V, Overton ET, Girard PM, Oka S, Walmsley S, Bettacchi C, Brinson C, Philibert P, Lombaard J, St Clair M, Crauwels H, Ford SL, Patel P, Chounta V, D'Amico R, Vanveggel S, Dorey D, Cutrell A, Griffith S, Margolis DA, Williams PE, Parys W, Smith KY, Spreen WR. Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection. N Engl J Med. 2020 Mar 19;382(12):1124-1135. doi: 10.1056/NEJMoa1909512. Epub 2020 Mar 4.
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
ViiV Healthcare
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries