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Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine From Current Antiretroviral Regimen in Virologically Suppressed HIV-1-infected Adults

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ClinicalTrials.gov Identifier: NCT02951052
Recruitment Status : Active, not recruiting
First Posted : November 1, 2016
Last Update Posted : June 6, 2018
Sponsor:
Collaborators:
Janssen Pharmaceuticals
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare

Brief Summary:
The Antiretroviral Therapy as Long Acting Suppression (ATLAS) study is being conducted to establish if human immunodeficiency virus type-1 (HIV-1) infected adult participants with current viral suppression on a regimen with 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus a third agent, remain suppressed upon switching to a two-drug intramuscular (IM) long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). This is a Phase 3, multi-phase, randomized, open label, active-controlled, multicenter, parallel-group, non-inferiority study in HIV-1, antiretroviral therapy (ART)-adult participants who are stably suppressed on a current antiretroviral (ARV) regimen. 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 with maintenance of current ARV regimen containing 2 NRTIs plus an INI, NNRTI, or a PI. Eligible participants will be randomized (1:1) into the Maintenance Phase at Day 1 to either continue current ART or switch to initiate oral therapy with CAB 30 mg + RPV 25 mg once daily for 4 Weeks followed by Q4 weekly (monthly) CAB LA + RPV LA injections. Following the Maintenance phase at Week 52, participants who were randomized to continue their current ART regimen will be given an option to switch to CAB LA + RPV LA injections. Those participants would transition to LA dosing, beginning with 4 weeks oral CAB + RPV therapy at Week 52, and receive the first IM CAB LA + RPV LA injections at Week 56.

Condition or disease Intervention/treatment 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: 2 NRTIs plus an INI, NNRTI, or PI Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 570 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Multicenter, Parallel-group, Non-inferiority, Open-label Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine From Current INI- NNRTI-, or PI-based Antiretroviral Regimen in HIV-1-infected Adults Who Are Virologically Suppressed
Actual Study Start Date : October 28, 2016
Estimated Primary Completion Date : May 29, 2018
Estimated Study Completion Date : February 16, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Rilpivirine

Arm Intervention/treatment
Experimental: CAB LA + RPV LA every 4 weeks
Eligible participants receive Oral CAB 30 mg + RPV 25 mg once daily for four weeks, IM CAB LA 600 mg and RPV LA 900 mg for the first injection, and Week 4 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: Current antiretroviral regimen
Eligible participants will continue their current anti-retroviral regimen (2 NRTIs plus an INI, NNRTI, or a PI) for 52 weeks. After 52 weeks participants have the option to continue study participation by switching to CAB LA + RPV LA in the Extension Phase where they will follow the procedure of CAB LA + RPV LA arm.
Drug: 2 NRTIs plus an INI, NNRTI, or PI

Acceptable stable (initial or second) ARV regimens include 2 NRTIs plus:

  • INI with the exception of ABC/DTG/3TC (either the initial or second cART regimen)
  • NNRTI (either the initial or second cART regimen)
  • Boosted PI (or atazanavir [ATV] unboosted) (either the initial or second PI-based cART regimen)




Primary Outcome Measures :
  1. Proportion of participants with plasma HIV 1 Ribonucleic acid <50 copies/millilitre (c/mL) at Week 48 [ Time Frame: Week (Wk) 48 ]
    Proportion of participants with a virologic failure analyzed by Food 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 :
  1. Proportion of participants with Plasma HIV-1 RNA <50 copies/mL (c/mL) [ Time Frame: Up to week 96 ]
    Assessed using the FDA Snapshot algorithm at week 48 and week 96. It is a key secondary endpoint

  2. 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

  3. Proportion of participants with confirmed virologic failure [ Time Frame: Up to week 96 ]
    Two consecutive plasma HIV-1 RNA levels ≥200 c/mL after prior suppression to <200 c/mL. Assessed at week 48 and week 96

  4. Change from Baseline in plasma HIV-1 RNA [ Time Frame: Baseline and up to week 96 ]
    Analyzed at week 48 and week 96

  5. Changes from Baseline in CD4+ cell counts [ Time Frame: Baseline and up to week 96 ]
    Analyzed at week 48 and week 96

  6. Incidence of disease progression [ Time Frame: Up to week 96 ]
    Assessed by HIV-associated conditions, acquired immunodeficiency syndrome (AIDS) and death at week 48 and week 96

  7. Incidence and severity of adverse events (AEs) [ Time Frame: Up to Wk 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 at Week 48 and week 96

  8. Incidence and severity of laboratory abnormalities [ Time Frame: Up to Wk 96 ]
    Incidence and severity will be analyzed at Week 48 and Week 96

  9. Proportion of participants who discontinue treatment due to AEs [ Time Frame: Up to Wk 96 ]
    Participants who discontinue treatment due to AEs at Week 48 and Week 96 will be analyzed

  10. Number of participants having changes in laboratory parameters [ Time Frame: Baseline and up to Wk 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 Week 48 and Week 96

  11. Incidence of treatment emergent resistance [ Time Frame: Baseline and up to Wk 96 ]
    Genotypic and phenotypic resistance to CAB, RPV, and other on-study antiretroviral treatment (ART) at Week 48 and Week 96

  12. Plasma trough concentration (Ctrough) for CAB LA [ Time Frame: Wk 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, and 96 for intramuscular arm (IM)and Wk 60 for participants transitioning to IM arm ]
    Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at , 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 96 in intramuscular (IM) arm and at Wk 60 for participants transitioning to CAB LA + RPV LA from ART group

  13. Plasma trough concentration (Ctrough) for RPV LA [ Time Frame: Wk 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, and 96 for intramuscular arm (IM)and Wk 60 for participants transitioning to IM arm ]
    Blood sample will be obtained from Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at , 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 96 in intramuscular (IM) arm and at Wk 60 for participants transitioning to CAB LA + RPV LA from ART group

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

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

  16. Plasma area under the concentration-time curve (AUC) for CAB LA [ Time Frame: Wk 5, 8, 12, 16, 20, 24, 28, 32, 36, 40, 41, 44, 48, 52, 56, and 96 ]
    Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 96 in IM arm. Post-dose sample will be collected at Wk 5, Wk 41

  17. Plasma area under the concentration-time curve (AUC) for RPV LA [ Time Frame: Wk 5, 8, 12, 16, 20, 24, 28, 32, 36, 40, 41, 44, 48, 52, 56, and 96 ]
    Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 96 in IM arm. Post-dose sample will be collected at Wk 5, Wk 41

  18. Proportion of participants with a virologic failure analyzed by FDA Snapshot algorithm [ Time Frame: Wk 96 ]
    As per FDA Snapshot algorithm virological failure will be determined on the basis of participants who missed, switched or discontinued the treatment

  19. Acceptance of injection-related pain and injection site reactions (ISRs) (for CAB LA + RPV LA) [ Time Frame: Week 4 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

  20. Change from baseline in health related quality of life (HAT-Qol) [ Time Frame: Baseline to Wk 96 ]
    HR QoL will be assessed in Day 1 and Week 24, Week 48, Week 96

  21. Change from baseline in treatment satisfaction [ Time Frame: Baseline and up to Wk 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 Baseline (Day 1) and weeks 4b, 24, 44, 96 and/or WD. The change from baseline in HIVTSQs total score at Week 44 is a key secondary endpoint

  22. Change from previous therapy in treatment satisfaction [ Time Frame: Baseline up to Week 48 ]
    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 96 and/or WD

  23. Change in health status [ Time Frame: Baseline to Wk 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 Baseline (Day 1) and weeks 24, 48, 96 and/or WD

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

  25. Change in tolerability of injection from Week 4b, Week 5, Week 40, Week 41, and Week 96. [ Time Frame: Baseline to Wk 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

  26. 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.

  27. 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.

  28. 1 Week Post Dose concentration of CAB and RPV in all participants randomized to CAB LA and RPV LA [ 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.

  29. 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.

  30. 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.

  31. 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.

  32. 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.



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

Inclusion Criteria:

  • HIV-1 infected men or women aged 18 years or greater at the time of signing the informed consent.
  • Must be on uninterrupted current regimen (either the initial or second ARV regimen) for at least 6 months prior to Screening. Any prior switch, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability/safety, access to medications, or convenience/simplification, and must not have been done for treatment failure (HIV-1 RNA >=400 cells/milliliter [c/mL]).
  • Acceptable stable (initial or second) ARV regimens prior to Screening include 2 NRTIs plus: INI with the exception of ABC/DTG/3TC (either the initial or second cART regimen); NNRTI (either the initial or second cART regimen); Boosted PI (or atazanavir [ATV] unboosted) (either the initial or second PI-based cART regimen).
  • Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12 months prior to Screening: one within the 6 to 12 month window, and one within 6 months prior to Screening;
  • Plasma HIV-1 RNA <50 c/mL at Screening;
  • A female participant is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test at screen and a negative urine hCG test at Randomization), not lactating, and at least one of the following conditions applies: Non-reproductive potential defined as: Pre-menopausal females with either Documented tubal ligation; Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; Hysterectomy; Documented Bilateral Oophorectomy. Postmenopausal is 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 and until 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.
  • Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. Eligible participants or their legal guardians must sign a written Informed Consent Form before any protocol-specified assessments are conducted.
  • Participants enrolled in France must be affiliated to, or a beneficiary of, a social security category.
  • All participants participating in the study should be counseled on safer sexual practices including the use and benefit/risk of effective barrier methods (example: male condom) and on the risk of HIV transmission to an uninfected partner.

Exclusion Criteria:

  • Within 6 months prior to Screening and after confirmed suppression to <50 c/mL on current ART regimen, any plasma HIV-1 RNA measurement >=50 cells/milliliter (c/mL).
  • Within the 6 to 12 month window prior to Screening and after confirmed suppression to <50 c/mL, any plasma HIV-1 RNA measurement >200 c/mL, or 2 or more plasma HIV-1 RNA measurements >=50 c/mL.
  • Any drug holiday during the window between initiating first HIV ART and 6 months prior to Screening, except for brief periods (less than 1 month) where all ART was stopped due to tolerability and/or safety concerns.
  • Any switch to a second line regimen, defined as change of a single drug or multiple drugs simultaneously, due to virologic failure to therapy (defined as a confirmed plasma HIV 1 RNA measurement >=400 c/mL after initial suppression to <50 c/mL while on first line HIV therapy regimen).
  • Abacavir/dolutegravir/lamivudine, (ABC/DTG/3TC) as current ART regimen.
  • A history of use of any regimen consisting of only single NNRTI therapy (even if only for peri-partum treatment), or only single or dual NRTI therapy prior to starting cART.
  • Participants who are currently participating in or anticipate to be selected for any other interventional study.
  • Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the study.
  • Any evidence of an active Center for Disease Control and Prevention (CDC) Stage 3 disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy and historical or current cluster of differentiation 4 (CD4) cell counts less than 200 copies per cubic meter (c/mm^3).
  • Participants with 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.
  • 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.
  • Participants who, in the investigator's judgment, pose 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 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 within 12 months 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, and 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 inconclusive, the Fib-4 score will be used to verify eligibility. 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 or cirrhosis), 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.
  • 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.
  • Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require agreement between the Investigator and the Study medical monitor for inclusion of the participant prior to randomization.
  • Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the study drugs 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 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 with the exception of the use of low dose acetylsalicylic acid (=<325mg).
  • Any evidence of primary resistance based on the presence of any major known INI or non-nucloside reverese transcriptase inhibitors (NNRTI) resistance-associated mutation, except for K103N, by any historical resistance test result.
  • 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 creatine clearance <50 mL/min per 1.73 square meter (m^2) via Chronic Kidney Disease Epidemiology (CKD-EPI) Method.
  • Alanine aminotransferase (ALT) >=3 x upper limit of normal (ULN).
  • Exposure to an experimental drug or experimental vaccine within either 30 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to Day 1 of this study.
  • Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; tuberculosis therapy with the exception of isoniazid (isonicotinylhydrazid, INH); anti-coagulation agents. Immunomodulators that alter immune responses (such as systemic corticosteroids, interleukins, or interferons. Note: Participants using short-term (<1 day) steroid tapers, topical, inhaled and 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 study Day 1.
  • Use of medications which are associated with Torsades de Pointes.
  • Current or prior history of etravirine (ETR) use.
  • Current use of tipranavir/ritonavir or fosamprenavir/ritonavir.
  • Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication. Note: Any prohibited medications that decrease CAB or RPV concentrations should be discontinued for a minimum of four weeks or a minimum of three half-lives (whichever is longer) prior to the first dose and any other prohibited medications should be discontinued for a minimum of two weeks or a minimum of three half-lives (whichever is longer) prior to the first dose.

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): NCT02951052


  Show 119 Study Locations
Sponsors and Collaborators
ViiV Healthcare
Janssen Pharmaceuticals
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials ViiV Healthcare

Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT02951052     History of Changes
Other Study ID Numbers: 201585
First Posted: November 1, 2016    Key Record Dates
Last Update Posted: June 6, 2018
Last Verified: June 2018

Keywords provided by ViiV Healthcare:
Long-acting cabotegravir
Virologic failure
long-acting rilpivirine
Antiretroviral

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
Rilpivirine
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