Trial from ClinicalTrials.gov

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Trial ID
NCT02500446
Ethics application status
Date submitted
30/06/2015
Date registered
30/06/2015
Date last updated
3/05/2017

Titles & IDs
Public title
Dolutegravir Impact on Residual Replication
Scientific title
Dolutegravir Impact on Residual Replication: Dolutegravir Intensification Study
Secondary ID [1] 0 0
DIORR_20150306
Universal Trial Number (UTN)
Trial acronym
DIORR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: drugs - dolutegravir
Other interventions - Placebo

Active Comparator: Intensification - Oral dolutegravir 50 mg once daily for 8 weeks added to their current ART regimen.

Placebo Comparator: Placebo - Oral placebo once daily for 8 weeks added to their current ART regimen.


Treatment: drugs: dolutegravir
Each film-coated tablet contains dolutegravir sodium equivalent to 50 mg dolutegravir.

Other interventions: Placebo
A film-coated tablet identical in appearance to the active drug tablet but not containing any dolutegravir or any other active ingredient

Intervention code [1] 0 0
Treatment: drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Level of residual HIV replication in circulating CD4+ T cells - Change in the level of 2-LTR circles as measured by polymerase chain reaction (PCR) in the dolutegravir arm versus the placebo arm after 7 days of treatment
Timepoint [1] 0 0
day 7 of treatment
Secondary outcome [1] 0 0
Level of Human Leukocyte Antigen D-related (HLA-DR) - Change in level of Human Leukocyte Antigen D-related (HLA-DR), a marker of T cell activation from baseline within and across study arms.
Timepoint [1] 0 0
time points to day 84 (28 days after treatment)
Secondary outcome [2] 0 0
Level of Programmed cell death-1 receptor (PD-1) - Change in level of Programmed cell death-1 receptor (PD-1), a marker of T cell activation from baseline within and across study arms.
Timepoint [2] 0 0
time points to day 84 (28 days after treatment)
Secondary outcome [3] 0 0
Level of Cluster of Differentiation 38 (CD-38) - Change in level of Cluster of Differentiation 38 (CD-38), a marker of T cell activation, from baseline within and across study arms.
Timepoint [3] 0 0
time points to day 84 (28 days after treatment)
Secondary outcome [4] 0 0
Level of residual HIV replication in circulating CD4+ T cells in a protease inhibitor -containing regimen - Change in the level of 2-LTR circles as measured by polymerase chain reaction (PCR) in the dolutegravir arm versus the placebo arm in those participants on regimen which includes a protease inhibitor
Timepoint [4] 0 0
time points up to day 84 (28 days after treatment)

Eligibility
Key inclusion criteria
- Documented HIV-1 infection

- Minimum age 18 years

- Receiving combination ART (at least 3 agents) for at least 3 years. Twenty of the 40
study participants will be on a PI-based ART regimen.

- HIV-1 plasma RNA <50 copies/mL for >3 years and <20 copies/mL at screening.

- Two CD4+ T cell counts >350 cells/µL in the 24 months prior to screening

- Able to give informed consent

- A female, may be eligible to enter and participate in the study if she:

- Is of non-child-bearing potential OR

- Is of child-bearing potential with a negative pregnancy test at both Screening
and Day 1 and agrees to use one of the study protocol-specified methods of
contraception to avoid pregnancy:
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Known hypersensitivity to DTG or to any of the excipients

- Current use of dofetilide, pilsicainide or metformin

- Current use of etravirine except when etravirine is co-administered with
atazanavir/ritonavir, lopinavir/ritonavir or darunavir/ritonavir

- Current or prior use of any integrase inhibitor

- Previous use of histone deacetylase inhibitors or other latency reversing agents

- Any significant acute medical illness requiring hospitalization within preceding 8
weeks

- Significant renal disease (eGFR <50 milliliters per min)

- Hepatitis C co-infection (Individuals with prior hepatitis C infection that is now
cleared are eligible for enrolment)

- Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh
classification

- Unstable liver disease (as defined by the 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)

- Receipt of immunomodulating agents (excluding immunization) or systemic
chemotherapeutic agents within 28 days prior to study entry

- Patients who intend to modify their ART regimen within the study period

- Current or recent gastrointestinal disease or surgery that may impact the absorption
of the investigational drug

- Active alcohol or substance use that in the opinion of the investigator will prevent
adequate compliance with study procedures

- Currently pregnant, breastfeeding or unwilling to use barrier contraception

- Women of Child Bearing Potential (WOCBP) unwilling or unable to use an acceptable
method of contraception to avoid pregnancy as specified in the inclusion criteria

- Unable or unwilling to adhere to protocol procedures

- The following laboratory values within 3 weeks before starting the investigational
drug (lab tests may be repeated to obtain acceptable values before failure at
screening is concluded)

- Hepatic transaminases (AST or ALT) =3 x upper limit of normal (ULN)

- Serum total bilirubin =1.5 x ULN

- eGFR <50 mL/min

- Haemoglobin <11.0 g/dL

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Current
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Melbourne Sexual Health Centre - Carlton
Recruitment hospital [2] 0 0
Alfred Hospital - Prahran
Recruitment postcode(s) [1] 0 0
3053 - Carlton
Recruitment postcode(s) [2] 0 0
3010 - Prahran

Funding & Sponsors
Primary sponsor type
Other
Name
University of Melbourne
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
The Alfred
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
ViiV Healthcare
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Several studies have suggested that despite suppressive combination antiretroviral therapy
(ART) in people who are HIV-positive, in some individuals there may be on-going viral
replication. Clarifying the extent of on-going viral replication on ART is important for the
development of HIV-1 curative strategies and for reducing HIV-1 associated immune activation.
The investigators hypothesize that treatment intensification with dolutegravir will inhibit
residual virus replication in HIV-1 infected patients on ART. The primary objective of this
study is to determine the effects of dolutegravir intensification on residual virus
replication in circulating cluster of differentiation 4 (CD4+) T cells.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sharon Lewin
Address 0 0
Doherty Institute for Immunity and Infection
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
Contact person responsible for updating information