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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03635788




Registration number
NCT03635788
Ethics application status
Date submitted
15/08/2018
Date registered
17/08/2018

Titles & IDs
Public title
The LATITUDE Study: Long-Acting Therapy to Improve Treatment SUccess in Daily LifE
Scientific title
A Phase III Study to Evaluate Long-Acting Antiretroviral Therapy in Non-Adherent HIV-Infected Individuals
Secondary ID [1] 0 0
30104
Secondary ID [2] 0 0
ACTG A5359
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 - Standard of Care (SOC) Oral ART
Treatment: Drugs - Oral RPV
Treatment: Drugs - Oral CAB
Treatment: Drugs - RPV-LA Loading Dose
Treatment: Drugs - CAB-LA Loading Dose
Treatment: Drugs - RPV-LA Maintenance Dose
Treatment: Drugs - CAB-LA Maintenance Dose

Experimental: Arm A: LA ART - In Step 1, participants will receive SOC oral ART regimen for up to 24 weeks. In Step 2, participants will receive oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks. In Step 3, participants will receive a RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks until the end of Step 2. In Step 4, eligible participants will be followed until they complete 52 weeks on locally sourced oral ART.

Active comparator: Arm B: SOC Oral ART - In Step 1, participants will receive SOC oral ART regimen for up to 24 weeks. In Step 2, participants will continue SOC oral ART regimen for 52 weeks. In Step 3, participants will receive oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and CAB-LA maintenance dose every 4 weeks until the end of Step 3. In Step 4, eligible participants will be followed until they complete 52 weeks on locally sourced oral ART.


Treatment: Drugs: Standard of Care (SOC) Oral ART
SOC oral ART regimen must include at least 3 drugs with 2 or more drugs predicted to be fully active, including a boosted protease inhibitor (PI) and/or an integrase strand transfer inhibitor (INSTI)

Treatment: Drugs: Oral RPV
RPV 25 mg tablets

Treatment: Drugs: Oral CAB
CAB 30 mg tablets

Treatment: Drugs: RPV-LA Loading Dose
900 mg administered as one 3 mL (900 mg) intramuscular injection in the gluteal muscle

Treatment: Drugs: CAB-LA Loading Dose
600 mg administered as one 3 mL (600 mg) intramuscular injection in the gluteal muscle

Treatment: Drugs: RPV-LA Maintenance Dose
600 mg administered as one 2 mL (600 mg) intramuscular injection in the gluteal muscle

Treatment: Drugs: CAB-LA Maintenance Dose
400 mg administered as one 2 mL (400 mg) intramuscular injection in the gluteal muscle
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Occurrence of regimen failure in Step 2
Timepoint [1] 0 0
From after Step 2 randomization to Step 2, Week 48
Secondary outcome [1] 0 0
Occurrence of virologic failure in Step 2 at any time post randomization and week 48 visit
Timepoint [1] 0 0
from after Step 2 randomization to Step 2, Week 48
Secondary outcome [2] 0 0
Occurrence of the treatment-related failure in Step 2 at any time post randomization and week 48 visit
Timepoint [2] 0 0
from after Step 2 randomization to Step 2, Week 48
Secondary outcome [3] 0 0
Number of participants with virologic non-success
Timepoint [3] 0 0
from after Step 2 randomization to Step 2, Week 48]
Secondary outcome [4] 0 0
Number of participants with plasma HIV-1 RNA level less than 50 copies/mL and less than or equal to 200 copies/mL at scheduled study visits on Steps 1 and 2
Timepoint [4] 0 0
Measured from Step 1 entry through Step 2, Week 52
Secondary outcome [5] 0 0
Frequency of AEs during Steps 1 and 2
Timepoint [5] 0 0
Measured from Step 1 entry through Step 2, Week 52
Secondary outcome [6] 0 0
Occurrence of discontinuation of randomized treatment in Step 2
Timepoint [6] 0 0
Measured from after Step 2 randomization through Step 2, Week 48
Secondary outcome [7] 0 0
Summary score of HIV Treatment Satisfaction Questionnaire (HIVTSQ) in Step 2
Timepoint [7] 0 0
Step 2 randomization, Step 2 weeks 24 and 48
Secondary outcome [8] 0 0
Frequency of missed or delayed injections for participants who received LA ART in Step 2
Timepoint [8] 0 0
Measured from Step 2 randomization through Step 2, Week 52
Secondary outcome [9] 0 0
Summary scores of HIV Treatment Adherence Self-Efficacy Scale in Step 1 and Step 2
Timepoint [9] 0 0
Measured from Step 1 through Step 2, Week 52
Secondary outcome [10] 0 0
Frequency of new drug-resistance mutations in participants with virologic failure in Step 2
Timepoint [10] 0 0
Measured from after Step 2 randomization through Step 2, Week 52
Secondary outcome [11] 0 0
Frequency of Injection Site Reactions (ISR) during Step 2
Timepoint [11] 0 0
Measured from Step 2 randomization through Step 2, Week 52
Secondary outcome [12] 0 0
Summary of participant self-reported dichotomous preference questionnaire
Timepoint [12] 0 0
Step 2 week 48

Eligibility
Key inclusion criteria
Step 1 Inclusion Criteria

• HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.

* NOTE: The term "licensed" refers to a FDA-approved kit, which is required for all IND studies.
* WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
* HIV-1 Plasma viral load (VL) greater than 200 copies/mL within 12 months prior to study entry by any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, unless participant has been lost to clinical follow-up (see protocol for more information) and no viral load result is available within the last 12 months

NOTE: Participants who satisfy non-adherence eligibility due to loss to clinical follow-up ) may not have a viral load result available at the time of consideration for eligibility. Those participants can be screened and, regardless of their screening viral load result (either = or >200 copies/mL), they would be eligible for study entry if they meet all other inclusion/exclusion criteria.

Evidence of non-adherence to ART according to at least one of the following criteria:

* Poor virologic response within 18 months prior to study entry (defined as less than 1 log10 decrease in HIV-1 RNA or HIV-1 RNA greater than 200 copies/mL at two time points at least 4 weeks apart) in individuals who have been prescribed ART for at least 6 consecutive months.
* Lost to clinical follow-up within 18 months prior to study entry with ART non-adherence for greater than or equal to 6 consecutive months.
* NOTE: Lost to clinical follow-up is defined as either no contact with provider or missed greater than or equal to 1 appointment in a 6-month period. ART non-adherence is defined as a lapse in ART greater than or equal to 7 days (consecutive or non-consecutive), in the 6-month period where they were lost to clinical follow-up per participant report.
* No evidence of any clinically relevant RPV or INSTI resistance-associated mutations (see protocol for more information) through commercially available genotypic (or phenotypic, if available) analyses from any laboratory that has a CLIA certification or equivalent within 60 days of study entry (see protocol for more information), nor history of such mutations on review of prior HIV-1 drug resistance tests by the site investigator. For participants in whom a screening HIV-1 conventional genotype cannot be resulted by the testing laboratory, review of historical genotypes and treatment history by the IoR can be used to satisfy this criterion as indicated in the protocol.
* Ability of site clinician, in conjunction with participant, to construct an oral induction antiretroviral (ARV) regimen that must include at least three ARVs of which at least two must be predicted to be fully active. The regimen must, include PI/cobi and/or an INSTI based on screening and/or historic resistance testing.

Laboratory values obtained within 60 days prior to study entry by any laboratory that has a CLIA certification or its equivalent:

* Hemoglobin greater than or equal to 9.0 g/dL
* Absolute neutrophil count (ANC) greater than or equal to 600/mm^3
* Alanine aminotransferase (ALT) less than or equal to 3 x upper limit of normal (ULN)
* Creatinine Clearance (CrCl) greater than or equal to 50 mL/min estimated by Chronic Kidney Disease Epidemiology Collaboration equation (CKD-Epi )

For participants of reproductive potential, negative serum or urine pregnancy test with a sensitivity of less than or equal to 25 mIU/mL at screening. This will be repeated again at study entry.

* NOTE: Participants are considered to be NOT of reproductive potential if: 1) they have had amenorrhea for at least 12 consecutive months prior to study entry ((i.e., who have had no menses within 12 months prior to study entry), and have a documented follicle-stimulating hormone (FSH) greater than 40 IU/mL; OR 2) an FSH level is not available, but they have had 24 consecutive months of amenorrhea (in the absence of medications known to induce amenorrhea); OR 3) they report having undergone surgical sterilization (e.g., hysterectomy, or bilateral oophorectomy, or bilateral tubal ligation/hysteroscopic tubal occlusion).

Contraception Requirements

Participants of Reproductive Potential: Participants of reproductive potential, who are participating in sexual activity that could lead to pregnancy, must agree to use at least one of the listed highly effective methods for contraception from 30 days prior to the first dose of study medication, while receiving the study drugs, and for 30 days after stopping oral medications, or the duration specified in the product label if receiving study drugs not supplied by the study, or 52 weeks after stopping RPV-LA or CAB-LA. Acceptable methods of contraception include:

* Contraceptive subdermal implant
* Intrauterine device or intrauterine system
* Combined estrogen and progestogen oral contraceptive
* Injectable progestogen
* Contraceptive vaginal ring
* Percutaneous contraceptive patches
* Participants Who Are Not of Reproductive Potential: Participants who are not of reproductive potential are eligible to start study drugs without requiring the use of contraceptives. Any statement of self-reported sterility or that of her partner's must be entered in the source documents.
* NOTE A: Acceptable documentation of lack of reproductive potential is the participant's self-reported history of surgical sterilization, menopause, or male partner's azoospermia.
* NOTE B: 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 a partner without HIV
* Age greater than or equal to 18 years.
* Ability and willingness of participant or legal guardian/representative to provide written informed consent.

Step 1
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

* Currently pregnant, planning to become pregnant during the study period, or currently breastfeeding.

Participants determined by the Site Investigator to have a high risk of seizures, including participants with an unstable or poorly controlled seizure disorder.

* NOTE: A participant with a prior history of seizure may be considered for enrollment if the Investigator believes the risk of seizure recurrence is low. All cases of prior seizure history should be discussed with the A5359 protocol leadership team (actg.leada5359@fstrf.org) prior to enrollment.
* Advanced 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 history of liver cirrhosis.
* Chronic Hepatitis C (HCV) with planned or anticipated use of anti-HCV therapy prior to the completion of Step 2.

History of or current active hepatitis B (HBV) infection defined as positive HBV surface antigen test or any detectable HBV DNA in participants with isolated HBcAb and HBV DNA as follows:

* Participants positive for HBsAg are excluded
* Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and any detectable 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. If prior documentation of immunity is available, repeat testing at screening is not required.
* Current or anticipated need for chronic anti-coagulation therapy.
* Unwilling to receive injections, or unable to receive gluteal injections.
* Tattoo or other condition over gluteus region, which may interfere with interpretation of injection site reaction.
* Previous use of CAB• Any acute or serious illness, within 7 days prior to entry,requiring systemic treatment and/or hospitalizationthat may render the participant unable to receive study medication, in the opinion of the site investigator..
* QTc greater than 450 ms using either Bazett or Fridericia method within 60 days prior to study entry: Whichever method is used at screening must be used throughout study period.
* Any serious medical or psychiatric condition, which may render the participant unable to receive study medication in the opinion of the site investigator.
* Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation.
* Requirement for any medication that is prohibited with a study medication (refer to protocol specific web page [PSWP]).

Step 2 Inclusion Criteria

* Meeting virologic suppression criteria at or after Step 1, week 4, defined as:

1. HIV-1 RNA =200 copies/mL

OR
2. HIV-1 RNA of 201-399 copies/mL followed by HIV-1 RNA =200 copies/mL by Step 1, week 24

NOTE: The HIV-1 RNA viral load that will be used to determine eligibility for randomization must have been collected within 4 weeks (28 days) of the Step 2 randomization visit.

Step 2 Exclusion Criteria
* Permanent discontinuation of study treatment for any reason during Step 1.
* Participants who never started study treatment in Step 1 (see protocol for more information)

Step 3 Inclusion Criteria, Participants Registering from Step 1

* Virologic suppression at or after Step 1, week 4, defined as:

1. HIV-1 RNA =200 copies/mL OR
2. HIV-1 RNA of 201-399 copies/mL followed by HIV-1 RNA =200 copies/mL by Step 1, week 24 NOTE: The HIV-1 RNA viral load that will be used to determine eligibility for Step 3 must have been collected within 4 weeks (28 days) of the Step 3 registration visit.
* Willingness to begin to receive LA ART.

Step 3 Exclusion Criteria, Participants Registering from Step 1

* Permanent discontinuation of study treatment for any reason during Step 1.
* Participants who never started study treatment in Step 1 (see protocol for more information.
* Currently pregnant, planning to become pregnant during the study period, or currently breastfeeding.

Step 3 Inclusion Criteria, Participants Registering from Step 2

* Willingness to continue LA ART (for those in Step 2 Arm A) or begin LA ART (for those in Step 2 Arm B).
* Step 2 Arm B participants: HIV-1 RNA =200 copies/mL at the most recent Step 2 visit OR Confirmation of Virologic Failure visit.

NOTE: The HIV-1 RNA viral load that will be used to determine eligibility for Step 3 must have been collected within 4 weeks (28 days) of the Step 3 registration visit.

Step 3 Exclusion Criteria, Participants Registering from Step 2

* Permanent discontinuation of study treatment (LA ART for Arm A and oral ART for Arm B) for any reason during Step 2.
* Confirmed Virologic Failure during Step 2.
* Step 2 Arm B Participants: Currently pregnant, planning to become pregnant during the study period, or currently breastfeeding.

Note: Step 2 Arm A participants who became pregnant and were permitted to continue on LA-ART may continue on that regimen in Step 3.

Step 4 Inclusion Criteria

* Any participant who has received at least one dose of CAB-LA or RPV-LA AND does not have access to available LA ART through their provider,
* OR does not wish to continue LA ART.

Step 4 Exclusion Criteria

• There are no exclusion criteria for Step 4.

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
28/03/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/08/2026
Actual
Sample size
Target
Accrual to date
Final
310
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
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
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
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
Tennessee
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Washington
Country [18] 0 0
Puerto Rico
State/province [18] 0 0
San Juan

Funding & Sponsors
Primary sponsor type
Government body
Name
National Institute of Allergy and Infectious Diseases (NIAID)
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
ViiV Healthcare
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Aadia Rana, M.D.
Address 0 0
Alabama CTU
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data that underlie results in the publication, after deidentification.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
Available to whom?
* With whom?

* Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group.
* For what types of analyses?

* To achieve aims in the proposal approved by the AIDS Clinical Trials Group.
* By what mechanism will data be made available?

* Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://submit.mis.s-3.net/. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03635788