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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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02938520
First Posted: October 19, 2016
Last Update Posted: October 11, 2017
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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Janssen Pharmaceuticals
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
  Purpose
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 particpants 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. At the end of the Maintenance phase, eligible participants who were randomized to continue ABC/DTG/3TC will be given an option to switch to LA therapy at Week 100. Those participants (HIV 1 RNA <50 c/mL at Week 96) will transition to LA dosing, beginning with approximately 4 weeks oral CAB + RPV therapy at Week 100, and receive the first IM CAB LA + RPV LA injections at Week 104b. 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.

Condition Intervention Phase
Infection, Human Immunodeficiency Virus Drug: Cabotegravir (CAB) tablet Drug: Rilpivirine (RPV) tablet Drug: Cabotegravir - Injectable Suspension (CAB LA) Drug: Rilpivirine - Injectable Suspension (RPV LA) Drug: ABC/DTG/3TC STR - Tablet Drug: DTG Tablet Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by ViiV Healthcare:

Primary Outcome Measures:
  • Proportion of participants with plasma HIV 1 Ribonucleic acid <50 copies/millilitre (c/mL) at Week 48. [ Time Frame: Week (Wk) 48 ]
    Virologic failure (HIV-1 RNA ≥ 50 c/mL) based on theFood and Drug Administration (FDA) Snapshot algorithm for the Intent-to-Treat Exposed population (subjects randomized and receiving at least one dose of investigational product during the Maintenance Phase)


Secondary Outcome Measures:
  • Proportion of participants with Plasma HIV-1 RNA <50 copies/mL (c/mL) at Week 48 [ Time Frame: Week 48 ]
    Assessed using the FDA Snapshot algorithm at Week 48 and is a key secondary endpoint.

  • Proportion of participants with plasma HIV-1 RNA <200 c/mL [ Time Frame: Up to Week 96 ]
    Assessed using the FDA Snapshot algorithm at Week 48 and Week 96

  • Proportion of participants with plasma HIV-1 RNA ≥ 50 c/mL at Week 96 [ Time Frame: Week 96 ]
    Proportion of participants with a virologic failure based on the FDA Snapshot algorithm for the Intent-to-Treat Exposed population (subjects randomized and receiving at least one dose of investigational product during the Maintenance Phase)

  • Proportion of participants with confirmed virologic failure [ Time Frame: Up to Week 96 ]
    For the purposes of clinical management in this study, virologic failure is defined as any of the following:Non-response as indicated by a less than a 1.0 log10 c/mL decrease in plasma HIV-1 RNA after 4 weeks of starting the Induction Phase, which is subsequently confirmed, unless the plasma HIV-1 RNA is < 400 c/mL (Induction Phase criteria), Rebound as indicated by two consecutive plasma HIV-1 RNA that are > 0.5 log10 c/mL increase in plasma HIV-1 RNA from the nadir value on study, where the lowest HIV-1 RNA value is ≥200 c/mL (Induction Phase criteria), Rebound as indicated by two consecutive plasma HIV-1 RNA levels ≥200 c/mL after prior suppression to < 200 c/mL. Analysed over time, including Week 48 and Week 96

  • Change from Baseline in plasma HIV-1 RNA [ Time Frame: Baseline and up to Week 96 ]
    Will be analyzed overtime, including Week 48 and Week 96

  • Changes from Baseline in CD4+ cell counts [ Time Frame: Baseline and up to Week 96 ]
    Will be analyzed overtime, including Week 48 and Week 96

  • Incidence of disease progression. [ Time Frame: Baseline and up to Week 96 ]
    Will be assessed overtime, including Week 48 and Week 96 (HIV-associated conditions, acquired immunodeficiency syndrome AIDS and death)

  • Incidence and severity of adverse events (AEs) [ Time Frame: Up to Week 96 ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgement will be categorized as serious adverse event (SAE). Incidence and severity will be analyzed overtime, including Week 48 and Week 96.

  • Incidence and severity of laboratory abnormalities [ Time Frame: Up to Week 96 ]
    Incidence and severity will be analyzed overtime, including Week 48 and Week 96

  • Proportion of participants who discontinue treatment due to AEs. [ Time Frame: Up to Week 96 ]
    Participants who discontinue treatment due to AEs will be analyzed overtime, including Week 48 and Week 96

  • Number of participants having changes in laboratory parameters. [ Time Frame: Baseline and up to Week 96 ]
    Laboratory parameters includes; 1. Hematology parameters-platelet count, red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin, hematocrit, mean corpuscular volume, WBC differential (includes; neutrophils, lymphocytes, monocytes, eosinophils and basophils), 2. Clinical chemistry- blood urea nitrogen, creatinine, fasting glucose, sodium, potassium, chloride, total carbon dioxide, lipase, Aspartate aminotransferase , Alanine aminotransferase, alkaline phosphatase, phosphate, total bilirubin, albumin, creatine phosphokinase, creatinine clearance will be analyzed over time, including Week 48 and Week 96

  • Change from Baseline in fasting lipids. [ Time Frame: Baseline and up to Week 96 ]
    Fasting lipid panel includes; Total cholesterol, high density lipid (HDL) cholesterol, low density lipid (LDL) cholesterol and triglycerides will be analyzed over time, including Week 48 and Week 96

  • Incidence of treatment emergent resistance [ Time Frame: Baseline and up to Week 96 ]
    Genotypic and phenotypic resistance to treatments; CAB, RPV, and other on-study antiretroviral treatment (ART) over time, including Week 48 and Week 96

  • Plasma trough concentration (Ctrough) for CAB LA arm [ Time Frame: Blood samples will be collected at Weeks 4b, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 96, 100, 104b, 108, and Withdrawal. ]
    Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at Wk 4b, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 96, 100 and 108 in IM arm and at Wk 104b and 108 for participants transitioning to CAB LA + RPV LA from ABC/DTG/3TC. Samples will also be obtained at the Withdrawal (WD) visit.

  • Plasma trough concentration (Ctrough) for RPV LA arm [ Time Frame: Blood samples will be collected at Weeks 4b, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 96, 100, 104b, 108, and Withdrawal ]
    Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at Wk 4b, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 96, 100 and 108 in IM arm and at Wk 104b and 108 for participants transitioning to CAB LA + RPV LA from ABC/DTG/3TC. Samples will also be obtained at the WD visit.

  • Maximum concentration (Cmax) in plasma for CAB LA arm [ Time Frame: Wk 5 and 41 ]
    Blood sample will be obtained from participants at Post-dose

  • Maximum concentration (Cmax) in plasma for RPV LA arm [ Time Frame: Wk 5 and 41 ]
    Blood sample will be obtained from participants at Post-dose

  • Plasma area under the concentration-time curve (AUC) for CAB LA arm [ Time Frame: Blood samples will be collected at Wk 4b, 5, 8, 12, 16, 20, 24, 28, 32, 36, 40, 41, 44, 48, 52, 56, 60, 96, 100, 104b, and 108. ]
    Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at Wk 4b, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 96, 100 and 108 in IM arm and at Wk 104b and 108 for participants transitioning to CAB LA + RPV LA from ABC/DTG/3TC. Post-dose sample will be collected at Wk 5, Wk 41 in IM arm.

  • Plasma area under the concentration-time curve (AUC) for RPV LA arm [ Time Frame: Blood samples will be collected at Wk 4b, 5, 8, 12, 16, 20, 24, 28, 32, 36, 40, 41, 44, 48, 52, 56, 60, 96, 100, 104b, and 108. ]
    Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at Wk 4b, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 96, 100 and 108 in IM arm and at Wk 104b and 108 for participants transitioning to CAB LA + RPV LA from ABC/DTG/3TC. Post-dose sample will be collected at Wk 5, Wk 41in IM arm.

  • Acceptance of injection-related pain and injection site reactions (ISRs) (for CAB LA + RPV LA) [ Time Frame: Week 5 to Week 96 ]
    The Perception of iNjection questionnaire (PIN) will be used to assess the following dimension scores: Bother of ISRs, Leg movement, Sleep, and Injection Acceptance. Additionally, individual PIN item scores will assess pain during injection, anxiety before and after injection, willingness to be injected in the future and overall satisfaction with mode of administration over time. PIN will be assessed at weeks 5, 41, 48, 96 and/or With drawal. Key secondary endpoints include the proportion of participants considering pain and local reactions following injection to be extremely or very acceptable based on the acceptability score after first injection and over time, and changes in the PIN acceptance score within the CAB LA + RPV LA arm over time.

  • Change from baseline in health related quality of life (HR QoL) [ Time Frame: Day 1 up to Week 96 ]
    HR QoL will be assessed using the HIV/AIDS-targeted quality of life (HAT-QOL) questionnaire short form on Day 1 and Week 24, Week 48, Week 96, (or WD)

  • Change from baseline in treatment satisfaction [ Time Frame: Day 1 up to Week 96 ]
    The HIV Treatment Satisfaction Questionnaire-status-12 (HIVTSQs-12) will be used to assess the "Total Treatment Satisfaction" score as well as the following sub-scale scores: "pain/discomfort" and "ease of administration. HIVTSQs-12 will be assessed at Day 1 and weeks 4b, 24, 44, 96 and/or WD. The change from baseline (Day 1) in HIVTSQs total score at Week 44 is a key secondary endpoint.

  • Change from previous therapy in treatment satisfaction [ Time Frame: Week 48 and/or WD ]
    The HIV Treatment Satisfaction Questionnaire-change-12 (HIVTSQc-12) will be used to assess the "Total Treatment Satisfaction" score as well as the following sub-scale scores: "pain/discomfort" and "ease of administration. It will assessed at Week 48 and/or WD

  • Change in health status [ Time Frame: Day 1 up to Week 96 ]
    Overall health status will be assessed with the 12-item Short Form Health Survey (SF-12) as well as the Physical and Mental Health component scores. SF-12 will be assessed at Day 1 and weeks 24, 48, 96 and/or WD

  • Change in treatment acceptance. [ Time Frame: Day 1 up to Week 96 ]
    Overall treatment acceptance to chronic therapy will be assessed with 3 items from the ACCEPT questionnaire. It will be assessed at Day 1 and weeks 8, 24, 48, 96 and/or WD

  • Change in tolerability of injection (for CAB LA + RPV LA) [ Time Frame: Week 4b and up to Week 96 ]
    Patient reported injection tolerability will be assessed in subjects receiving CAB LA + RPV LA using a single item 11-point Likert-based numeric rating scale (NRS) administered 30-60 minutes following the injections. NRS will be assessed at weeks 4b, 5, 40, 41, and 96

  • Pre-dose concentrations of CAB and RPV in all participants randomized to CAB LA and RPV LA. [ Time Frame: Pre-dose blood samples will be collected Week 4b, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 96, 100, 108, Withdrawal for analysis of CAB and RPV PK ]
    CAB and RPV trough concentrations and AUC will be determined in participants switching to CAB + RPV.

  • 2 Hours Post Dose concentrations of CAB and RPV in all participants randomized to CAB LA and RPV LA [ Time Frame: Week 4b, Week 48, Week 96 for analysis of CAB and RPV PK ]
    CAB and RPV concentrations immediately following injection with CAB LA and RPV LA will be determined in participants switching to CAB + RPV.

  • 1 Week Post Dose concentration of CAB and RPV in all participants randomized to CAB LA and RPV LA [ Time Frame: Time Frame: Week 5 and Week 41 for analysis of CAB and RPV PK ]
    CAB and RPV Cmax concentrations will be determined in participants switching to CAB + RPV.

  • Pre-Dose concentration for all participants switching to CAB + RPV from ABC/DTG/3TC [ Time Frame: Week 104b, 108, Withdrawal for analysis of CAB and RPV PK ]
    CAB and RPV trough concentrations will be determined in participants switching to CAB + RPV.

  • 2 Hour Post-Dose concentration for all participants switching to CAB + RPV from ABC/DTG/3TC [ Time Frame: Week 104b for analysis of CAB and RPV PK ]
    CAB and RPV concentrations immediately following injection with CAB LA and RPV LA will be determined in participants switching to CAB + RPV.

  • PK-pharmacodynamic (PD) assessment for CAB LA and RPV LA [ Time Frame: Up to Week 96 ]
    The PK-PD relationship will be explored between plasma PK parameters and plasma HIV-1 RNA, CD4+ cell counts and/or occurrence of AEs through Week 96 of the Maintenance Period.

  • Exposure-response relationship for CAB LA and RPV LA [ Time Frame: Up to Week 96 ]
    The exposure-response relationship will be explored between plasma PK parameters and age, sex, race, body weight, body mass index, and relevant laboratory parameters through Week 96 of the Maintenance Period.


Estimated Enrollment: 570
Study Start Date: October 27, 2016
Estimated Study Completion Date: June 17, 2022
Estimated Primary Completion Date: August 10, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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. until withdrawal
Drug: 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.
Drug: 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.
Drug: 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.
Drug: 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.
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, beginning with approximately 4 weeks of oral CAB + RPV therapy initiated at Week 100, and receive the first IM CAB LA + RPV LA injections at Week 104b.
Drug: 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.
Drug: 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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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: 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.
  • French participants will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

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 millimetre (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 systemic corticosteroids, interleukins, or interferons). Note: Participants using short-term (e.g. =<14 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02938520


  Show 112 Study Locations
Sponsors and Collaborators
ViiV Healthcare
Janssen Pharmaceuticals
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials ViiV Healthcare
  More Information

Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT02938520     History of Changes
Other Study ID Numbers: 201584
First Submitted: September 15, 2016
First Posted: October 19, 2016
Last Update Posted: October 11, 2017
Last Verified: October 2017

Keywords provided by ViiV Healthcare:
Antiretroviral agent
Maintenance
rilpivirine
dolutegravir
TMC278
Triumeq
non-nucleoside reverse transcriptase inhibitor
once monthly, every 4 weeks, once daily
GSK1265744
CAB
Tivicay
Long-Acting Intramuscular rilpivirine
lamivudine
integrase inhibitor
Long-Acting Intramuscular Cabotegravir
ART naïve
cabotegravir
abacavir

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Abacavir
Rilpivirine
Dolutegravir
Integrase Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
HIV Integrase Inhibitors