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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 : October 5, 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 subjects 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 subjects 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 subjects 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, subjects who were randomized to continue their current ART regimen will be given an option to switch to CAB LA + RPV LA injections. Those subjects 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)
Actual Enrollment : 618 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
Actual Primary Completion Date : May 29, 2018
Estimated Study Completion Date : February 8, 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 subjects 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 subjects will continue their current anti-retroviral regimen (2 NRTIs plus an INI, NNRTI, or a PI) for 52 weeks. After 52 weeks subjects 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 SUBJECTS WITH PLASMA HIV 1 RIBONUCLEIC ACID (RNA) >=50 COPIES/MILLILITRE (C/ML) AT WEEK 48 [ Time Frame: Week 48 ]
    Proportion of subjects 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 SUBJECTS WITH PLASMA HIV-1 RNA <50 COPIES/ML (C/ML) [ Time Frame: Week 48 ]
    Assessed using the FDA Snapshot algorithm at week 48. It is a key secondary endpoint

  2. PROPORTION OF SUBJECTS WITH PLASMA HIV-1 RNA <200 C/ML [ Time Frame: Week 48 ]
    Assessed using the Snapshot algorithm at week 48

  3. PROPORTION OF SUBJECTS WITH CONFIRMED VIROLOGIC FAILURE [ Time Frame: Week 48 ]
    Two consecutive plasma HIV-1 RNA levels ≥200 c/mL after prior suppression to <200 c/mL. Assessed at week 48

  4. CHANGE FROM BASELINE IN PLASMA HIV-1 RNA [ Time Frame: Baseline and Week 48 ]
    Analyzed at week 48

  5. CHANGES FROM BASELINE IN CD4+ CELL COUNTS [ Time Frame: Baseline and Week 48 ]
    Analyzed at week 48

  6. INCIDENCE OF DISEASE PROGRESSION [ Time Frame: Up to Week 48 ]
    Assessed by HIV-associated conditions, acquired immunodeficiency syndrome (AIDS) and death over 48 weeks

  7. NUMBER OF SUBJECTS WITH ADVERSE EVENTS (AES) AND SERIOUS ADVERSE EVENTS (SAE) [ Time Frame: Up to Week 48 ]
    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 judgment will be categorized as SAE.

  8. SEVERITY OF AES [ Time Frame: Up to Week 48 ]
    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 judgment will be categorized as SAE.

  9. NUMBER OF SUBJECTS WITH ABNORMAL LABORATORY PARAMETERS [ Time Frame: Up to Week 48 ]
    Incidence and severity will be analyzed at Week 48

  10. SEVERITY OF LABORATORY ABNORMALITIES [ Time Frame: Up to Week 48 ]
    Laboratory abnormalities will be automatically graded by the central lab according to the Division of AIDS toxicity scales

  11. PROPORTION OF SUBJECTS WHO DISCONTINUE TREATMENT DUE TO AES [ Time Frame: Up to Week 48 ]
    Subjects who discontinue treatment due to AEs will be analyzed

  12. NUMBER OF SUBJECTS HAVING CHANGES IN LABORATORY PARAMETERS [ Time Frame: Up to Week 48 ]
    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

  13. CHANGE FROM BASELINE IN FASTING LIPIDS [ Time Frame: Baseline and up to Week 48 ]
    Total cholesterol, high density lipoprotein, low density lipoprotein, and triglycerides will be analyzed

  14. CHANGE FROM BASELINE IN FASTING LIPIDS [ Time Frame: Baseline and up to Week 96 ]
    Total cholesterol, high density lipoprotein, low density lipoprotein, and triglycerides will be analyzed

  15. NUMBER OF SUBJECTS WITH TREATMENT EMERGENT RESISTANCE [ Time Frame: Week 48 ]
    Genotypic and phenotypic resistance to CAB, RPV, and other on-study antiretroviral treatment (ART) at Week 48

  16. PROPORTION OF SUBJECTS WITH VIROLOGIC FAILURE AS PER BASELINE THIRD AGENT TREATMENT CLASS [ Time Frame: Week 48 ]
    Assessed using the FDA Snapshot algorithm at week 48.

  17. PROPORTION OF SUBJECTS WITH PLASMA HIV-1 RNA <50 C/ML AS A MEASURE OF EFFICACY AS PER BASELINE THIRD AGENT TREATMENT CLASS [ Time Frame: Week 48 ]
    Assessed using the FDA Snapshot algorithm at week 48

  18. NUMBER OF SUBJECTS WITH AES AND SAES AS A MEASURE OF SAFETY AS PER BASELINE THIRD AGENT TREATMENT CLASS [ Time Frame: Up to Week 48 ]
    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 judgment will be categorized as SAE. Incidence and severity will be analyzed at Week 48

  19. SEVERITY OF AES AS A MEASURE OF SAFETY AS PER BASELINE THIRD AGENT TREATMENT CLASS [ Time Frame: Up to Week 48 ]
    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 judgment will be categorized as serious adverse event (SAE). Incidence and severity will be analyzed at Week 48

  20. NUMBER OF SUBJECTS WITH ABNORMAL LABORATORY PARAMETERES AS A MEASURE OF SAFETY AS PER BASELINE THIRD AGENT TREATMENT CLASS [ Time Frame: Up to Week 48 ]
    Incidence and severity will be analyzed at Week 48

  21. SEVERITY OF LABORATORY ABNORMALITIES AS A MEASURE OF SAFETY AS PER BASELINE THIRD AGENT TREATMENT CLASS [ Time Frame: Up to Week 48 ]
    Laboratory abnormalities will be automatically graded by the central lab according to the Division of AIDS toxicity scales

  22. PROPORTION OF SUBJECTS WHO DISCONTINUE TREATMENT DUE TO AES AS PER BASELINE THIRD AGENT TREATMENT CLASS [ Time Frame: Up to Week 48 ]
    Subjects who discontinue treatment due to AEs will be analyzed

  23. NUMBER OF SUBJECTS HAVING CHANGES IN LABORATORY PARAMETERS AS A MEASURE OF SAFETY AS PER BASELINE THIRD AGENT TREATMENT CLASS [ Time Frame: Up to Week 48 ]
    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

  24. NUMBER OF SUBJECTS WITH TREATMENT EMERGENT RESISTANCE AS PER BASELINE THIRD AGENT TREATMENT CLASS [ Time Frame: Up to Week 48 ]
    Genotypic and phenotypic resistance to CAB, RPV, and other on-study antiretroviral treatment (ART) at Week 48

  25. PLASMA TROUGH CONCENTRATION (CTROUGH) FOR CAB LA [ Time Frame: Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 96; 2 hours post-dose at Weeks 4, 48 and 96; 1 week post-dose at Weeks 5 and 41 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.

  26. PLASMA TROUGH CONCENTRATION (CTROUGH) FOR RPV LA [ Time Frame: Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 96; 2 hours post-dose at Weeks 4, 48 and 96; 1 week post-dose at Weeks 5 and 41. ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.

  27. MAXIMUM CONCENTRATION (CMAX) IN PLASMA FOR CAB LA ARM [ Time Frame: Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 96; 2 hours post-dose at Weeks 4, 48 and 96; 1 week post-dose at Weeks 5 and 41 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.

  28. MAXIMUM CONCENTRATION (CMAX) IN PLASMA FOR RPV LA ARM [ Time Frame: Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 96; 2 hours post-dose at Weeks 4, 48 and 96; 1 week post-dose at Weeks 5 and 41 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.

  29. PLASMA AREA UNDER THE CONCENTRATION-TIME CURVE (AUC) FOR CAB LA [ Time Frame: Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 96; 2 hours post-dose at Weeks 4, 48 and 96; 1 week post-dose at Weeks 5 and 41 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.

  30. PLASMA AREA UNDER THE CONCENTRATION-TIME CURVE (AUC) FOR RPV LA [ Time Frame: Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 96; 2 hours post-dose at Weeks 4, 48 and 96; 1 week post-dose at Weeks 5 and 41 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.

  31. NUMBER OF SUBJECTS WITH DIFFERENT DEMOGRAPHIC PARAMETERS FOR INTER-SUBJECT VARIABILITY [ Time Frame: Up to Week 96 ]
    Demographic parameters including, but not limited to, age, sex, race, body weight, body mass index, and relevant laboratory parameters will be evaluated as potential predictors of inter subject variability for pharmacokinetic parameters.

  32. PROPORTION OF SUBJECTS WITH PLASMA HIV-1 RNA <50 COPIES/ML (C/ML) DURING EXTENSION PHASE [ Time Frame: Up to Week 96 ]
    Assessed using the FDA Snapshot algorithm up to week 96.

  33. PROPORTION OF SUBJECTS WITH CONFIRMED VIROLOGIC FAILURE DURING EXTENSION PHASE [ Time Frame: Up to Week 96 ]
    Two consecutive plasma HIV-1 RNA levels ≥200 c/mL after prior suppression to <200 c/mL. Assessed up to week 96.

  34. CHANGE FROM BASELINE IN PLASMA HIV-1 RNA DURING EXTENSION PHASE [ Time Frame: Baseline and up to Week 96 ]
    Analyzed up to Week 96

  35. CHANGES FROM BASELINE IN CD4+ CELL COUNTS DURING EXTENSION PHASE [ Time Frame: Baseline and up to Week 96 ]
    Analyzed up to Week 96

  36. INCIDENCE OF DISEASE PROGRESSION DURING EXTENSION PHASE [ Time Frame: Up to Week 96 ]
    Assessed by HIV-associated conditions, acquired immunodeficiency syndrome (AIDS) and death up to Week 96

  37. NUMBER OF SUBJECTS WITH AES AND SAES DURING EXTENSION PHASE [ 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 judgment will be categorized as SAE. Incidence and severity will be analyzed at Week 48

  38. SEVERITY OF AES DURING EXTENSION PHASE [ 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 judgment will be categorized as serious adverse event (SAE).

  39. NUMBER OF SUBJECTS WITH ABNORMNAL LABORATORY PARAMETERS AS A MEASURE OF SAFETY DURING EXTENSION PHASE [ Time Frame: Up to Week 96 ]
    Incidence and severity will be analyzed at Week 96

  40. SEVERITY OF LABORATORY ABNORMALITIES AS A MEASURE OF SAFETY DURING EXTENSION PHASE [ Time Frame: Up to Week 96 ]
    Laboratory abnormalities will be automatically graded by the central lab according to the Division of AIDS toxicity scales

  41. PROPORTION OF SUBJECTS WHO DISCONTINUE TREATMENT DUE TO AES DURING EXTENSION PHASE [ Time Frame: Up to Week 96 ]
    Subjects who discontinue treatment due to AEs will be analyzed

  42. NUMBER OF SUBJECTS HAVING CHANGES IN LABORATORY PARAMETERS DURING EXTENSION PHASE [ Time Frame: 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 Week 48

  43. NUMBER OF SUBJECTS WITH ACCEPTANCE OF INJECTION-RELATED PAIN AND INJECTION SITE REACTIONS (ISRS) (FOR CAB LA + RPV LA) [ Time Frame: Up 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 Withdrawal .Key secondary endpoints include the proportion of subjects 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

  44. CHANGE FROM WEEK 5 IN DIMENSION SCORES USING THE PERCEPTION OF INJECTION QUESTIONNAIRE (PIN) [ 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 Withdrawal .Key secondary endpoints include the proportion of subjects 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

  45. CHANGE FROM BASELINE IN HEALTH RELATED QUALITY OF LIFE (HRQOL) [ Time Frame: Baseline and up to Week 96 ]
    HIV/AIDS-targeted quality of life questionnaire (HAT QoL) will be assessed

  46. CHANGE FROM BASELINE IN TOTAL TREATMENT SATISFACTION [ Time Frame: Baseline and 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 Baseline (Day 1) and weeks 4b, 24, 44, 96 and/or WD.

  47. CHANGE IN TREATMENT SATISFACTION OVER TIME [ Time Frame: Baseline and 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

  48. CHANGE FROM BASELINE IN HEALTH STATUS [ Time Frame: Baseline and 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 Baseline (Day 1) and weeks 24, 48, 96 and/or WD

  49. CHANGE FROM BASELINE IN TREATMENT ACCEPTANCE [ Time Frame: Baseline and 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 Baseline (Day 1) and weeks 8, 24, 48, 96 and/or WD

  50. CHANGE FROM WEEK 4B IN TOLERABILITY OF INJECTION [ Time Frame: Week 4b to Week 96 ]
    Subject 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



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, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged 18 years or older (or ≥19 where required by local regulatory agencies), 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 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) (must be either the initial cART regimen or one historical within class switch is permitted due to safety/tolerability) The addition, removal, or switch of a drug(s) that has been used to treat HIV based on antiretroviral properties of the drug constitutes a change in ART with the following limited exceptions: Historical changes in formulations of ART drugs or booster drugs will not constitute a change in ART regimen if the data support similar exposures and efficacy, and the change must have been at least 3 months prior to Screening; Historical perinatal use of an NRTI when given in addition to an ongoing HAART will not be considered a change in ART regimen; A change in dosing scheme of the same drug from twice daily to once daily will not be considered a change in ART regimen if data support similar exposures and efficacy.
  • 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 subjects 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:

    1. 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.
    2. Reproductive potential and agrees to 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 subjects 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. Eligible subjects or their legal guardians (and next of kin when locally required), must sign a written Informed Consent Form before any protocol-specified assessments are conducted. Enrolment of subjects who are unable to provide direct informed consent is optional and will be based on local legal/regulatory requirements and site feasibility to conduct protocol procedures.
  • Subjects enrolled in France must be affiliated to, or a beneficiary of, a social security category.
  • All subjects participating in the study should be counselled 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.

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 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
  • Subjects 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 [CDC, 2014], except cutaneous Kaposi's sarcoma not requiring systemic therapy and historical or current CD4 cell counts less than 200 cells/mm^3
  • Subjects with moderate to severe hepatic impairment
  • Any pre-existing physical or mental condition (including substance use disorder) which, in the opinion of the Investigator, may interfere with the subjects ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the subject.
  • Subjects determined by the Investigator to have a high risk of seizures, including subjects with an unstable or poorly controlled seizure disorder. A subject 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 subjects will be screened for syphilis (rapid plasma reagin [RPR]). Subjects with untreated syphilis infection, defined as a positive RPR without clear documentation of treatment, are excluded. Subjects with a serofast RPR result (persistence of a reactive nontreponemal syphilis test) despite history of adequate therapy and no evidence of re-exposure may enrol after consultation with the Medical Monitor. Subjects with a positive RPR test who have not been treated may be rescreened at least 30 days after completion of antibiotic treatment for syphilis
  • Subjects who, in the investigator's judgment, pose a significant suicide risk. Subject's recent history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk
  • The subject 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:•Subjects positive for HBsAg are excluded;
  • Subjects negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are 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; subjects 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) Subjects 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 subjects 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 ( sqr [ 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 subject 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 subject 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, subjects 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 NNRTI resistance-associated mutation, except for K103N, (International AIDS Society [IAS]-USA, 2015) 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 subject's participation in the study of an investigational compound
  • Subject has estimated creatine clearance <50mL/min per 1.73m^2 via CKDEPI Method
  • Alanine aminotransferase (ALT) ≥3 × 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 chronic systemic corticosteroids, interleukins, or interferons. Note: Subjects using short term (e.g. ≤21 days) systemic corticosteroid treatment; topical, inhaled and intranasal corticosteroids are eligible for enrolment.
  • 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 Torsade de Pointes.
  • Current or prior history of etravirine (ETR)
  • Current use of tipranavir/ritonavir or fosamprenavir/ritonavir
  • Subjects receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication.

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: October 5, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

Studies a U.S. FDA-regulated Device Product: No

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