Clinical trial NCT02951052: 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
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Infection, Human Immunodeficiency Virus
HIV Infections
Keywords: Long-acting cabotegravir
Virologic failure
long-acting rilpivirine
Antiretroviral
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
Collaborators: name: Janssen Pharmaceuticals
name: GlaxoSmithKline
First posted: 2016-11-01
Enrollment: 618
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Number of Participants With Virologic Failure (HIV-1 Ribonucleic Acid [RNA] >=50 Copies Per Millilter [mL]) Using Snapshot Algorithm at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Number of Participants With HIV-1 RNA <50 Copies/mL Using Snapshot Algorithm at Week 48
timeFrame: Week 48
measure: Number of Participants With HIV-1 RNA <200 Copies/mL Using Snapshot Algorithm at Week 48
timeFrame: Week 48
measure: Number of Participants With Confirmed Virologic Failure (CVF)
timeFrame: Weeks 8, 12, 20, 24, 32 and 40
measure: Absolute Values for Plasma HIV-1 RNA at Week 48
timeFrame: Week 48
measure: Change From Baseline Values for Plasma HIV-1 RNA
timeFrame: Baseline and Week 48
measure: Absolute Values for CD4+ Lymphocyte Count at Week 48
timeFrame: Week 48
measure: Change From Baseline Values for CD4+ Lymphocyte Count at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Number of Participants With Disease Progression
timeFrame: Up to Week 48
measure: Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Week 48
measure: Number of Participants With Severity of Adverse Events
timeFrame: Up to Week 48
measure: Absolute Values for Hematology Parameters Over Time Including Week 48: Basophil, Eosinophils, Leukocytes, Lymphocytes, Neutrophils, Monocytes, and Platelets
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Absolute Values for Hematology Parameters: Erythrocyte Mean Corpuscular Volume
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Absolute Values for Hematology Parameters: Erythrocytes
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Absolute Values for Hematology Parameters: Hemoglobin
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Absolute Values for Hematology Parameters: Hematocrit
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Change From Baseline for Hematology Parameters: Basophil, Eosinophils, Leukocytes, Lymphocytes, Neutrophils, Monocytes, and Platelets
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Change From Baseline for Hematology Parameters: Erythrocyte Mean Corpuscular Volume
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Change From Baseline for Hematology Parameters: Erythrocytes
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Change From Baseline for Hematology Parameters: Hematocrit
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Change From Baseline for Hematology Parameters: Hemoglobin
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Absolute Values for Clinical Chemistry Parameters Over Time Including Week 48: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatinine Kinase (CK)
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Albumin
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Absolute Values for Clinical Chemistry Parameters Over Time Including Week 48: Bilirubin, Direct Bilirubin and Creatinine
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Absolute Values for Clinical Chemistry Parameters: Total Carbon-dioxide (CO2), Chloride, Glucose, Phosphate, Potassium, Sodium and Urea Over Time Including Week 48
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Lipase
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Creatinine Clearance
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Number of Participants With Abnormal Urinalysis Parameters Over Time Including Week 48
timeFrame: Baseline (Day 1) and at Weeks 4, 24 and 48.
measure: Number of Participants With Urine Potential of Hydrogen (pH) Over Time Including Week 48
timeFrame: Baseline (Day 1) and at Weeks 4, 24 and 48
measure: Change From Baseline in Clinical Chemistry Parameters Over Time Including Week 48: ALT, ALP, AST and CK
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Albumin
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Change From Baseline Values for Clinical Chemistry Parameters Over Time Including Week 48: Bilirubin, Direct Bilirubin and Creatinine
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Change From Baseline Values for Clinical Chemistry Parameters Over Time Including Week 48
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Lipase
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Creatinine Clearance.
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Change From Baseline Values for Fasting Lipid Panel Over Time Including Week 48
timeFrame: Baseline (Day 1) and at Week 48
measure: Change From Baseline Values in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio Over Time Including Week 48
timeFrame: Baseline (Day 1) and at Weeks 4, 24 and 48
measure: Change From Baseline Values in Urine Creatinine Over Time Including Week 48
timeFrame: Baseline (Day 1) and at Weeks 4, 24 and 48
measure: Change From Baseline Values in Urine Phosphate Over Time Including Week 48
timeFrame: Baseline (Day 1) and at Weeks 4, 24 and 48
measure: Change From Baseline Values in Urine Retinol Binding Protein Over Time Including Week 48
timeFrame: Baseline (Day 1) and at Week 48
measure: Change From Baseline Values in Urine Specific Gravity Over Time Including Week 48
timeFrame: Baseline (Day 1) and at Weeks 4, 24 and 48
measure: Change From Baseline Values in Urine pH Over Time Including Week 48
timeFrame: Baseline (Day 1) and at Weeks 4, 24 and 48
measure: Number of Participants Who Discontinued or Withdrawn Due to AEs Over Time Including Week 48
timeFrame: Up to Week 48
measure: Percentage Change From Baseline in Fasting Lipids Overtime Including Week 48
timeFrame: Baseline (Day 1) and at Week 48
measure: Number of Participants With Phenotypic Resistance Through Week 48
timeFrame: At the time of CVF
measure: Number of Participants With Genotypic Resistance Through Week 48
timeFrame: At the time of CVF
measure: Number of Participants With AEs by Using Baseline Third Agent Treatment Class Overtime Including Week 48
timeFrame: Up to Week 48
measure: Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: ALT, ALP, AST and CK
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Albumin
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Bilirubin, Direct Bilirubin and Creatinine
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Creatinine Clearance
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Lipase
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Absolute Values for Fasting Lipid Panel Using Baseline Third Agent Treatment Class Overtime Including Week 48
timeFrame: Baseline (Day 1) and at Week 48
measure: Number of Participants Discontinued or Withdrawn Due to AEs When Baseline Third Agent Treatment Class Was Used Over Time Including Week 48
timeFrame: Up to Week 48
measure: Plasma Trough Concentration (Ctrough) for CAB LA Evaluable
timeFrame: Pre-dose at Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Ctrough for RPV LA Evaluable
timeFrame: Pre-dose at Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Area Under the Curve (AUC) for CAB LA
timeFrame: Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48; 1 Week post-dose at Weeks 5 and 41
measure: AUC for RPV LA
timeFrame: Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48; 1 Week post-dose at Weeks 5 and 41
measure: Maximum Concentration (Cmax) in Plasma for CAB LA Evaluable at Week 41
timeFrame: Week 41- 1 Week post dose
measure: Cmax in Plasma for RPV LA Evaluable at Week 41
timeFrame: Week 41- 1 Week post dose
measure: Percentage of Participants With a Virologic Failure Using Snapshot Algorithm by Baseline Third Agent
timeFrame: Week 48
measure: Percentage of Participants With Plasma HIV-1 RNA <50copies/mL Using Snapshot Algorithm by Baseline Third Agent
timeFrame: Week 48
measure: Number of Participants With Severity of Adverse Events by Baseline Third Agents
timeFrame: Up to Week 48
measure: Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: ALT, ALP, AST and CK
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Albumin
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Bilirubin, Direct Bilirubin and Creatinine
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Creatinine Clearance
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Lipase
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
measure: Change From Baseline Values for Fasting Lipid Panel Using Baseline Third Agent Treatment Class Overtime Including Week 48
timeFrame: Baseline (Day 1) and at Week 48
measure: Number of Participants With Genotypic Resistance Using Baseline Third Agent Through Week 48
timeFrame: At the time of CVF
measure: Number of Participants With Phenotypic Resistance Using Baseline Third Agent Through Week 48
timeFrame: At the time of CVF
measure: Change From Week 5 in Dimension Scores Using Percerption of Injection Questionnaire (PIN)-Last Observation Carried Forward (LOCF) in Q4W Arm
timeFrame: Week 5 and at Weeks 41 and 48
measure: Percentage of Participants With Extremely or Very Acceptable Pain and Local Reaction: Acceptability Score on PIN Questionnaire in Q4W Arm
timeFrame: Weeks 5, 41 and 48
measure: Change From Baseline in Life Satisfaction (LISAT) Using HIV/AIDs-targeted Quality of Life (HATQoL) Questionnaire
timeFrame: Baseline (Day 1) and at Weeks 24 and 48
measure: Change From Baseline in HIV Medication, MEDWO Using HATQoL
timeFrame: Baseline and at Weeks 24 and 48
measure: Change From Baseline in DISWO Using HATQoL
timeFrame: Baseline and at Weeks 24 and 48
measure: Change From Baseline in Health Status Using 12-item Short Form Survey (SF-12)
timeFrame: Baseline and at Weeks 24 and 48
measure: Change From Baseline in Total Treatment Satisfaction Using HIV Treatment Satisfaction Questionnaire (HIVTSQs) at Weeks 4b, 24 and 44
timeFrame: Baseline and at Weeks 4b, 24 and 44
measure: Change in Treatment Satisfaction Over Time Using HIVTSQ Change (HIVTSQc) at Week 48 in Q4W Arm
timeFrame: Week 48
measure: Change From Baseline in Treatment Acceptance at Weeks 8, 24 and 48 Using "General Acceptance" Dimension of the Chronic Treatment Acceptance (ACCEPT) Questionnaire
timeFrame: Baseline and at Weeks 8, 24 and 48
measure: Change From 4b in Tolerability of Injection at Week 5, 40 and 41 Using Numeric Rating Scale (NRS) Within CAB LA+RPV LA Arm
timeFrame: Weeks 4b, 5, 40 and 41
measure: Change From Baseline in Individual Item Scores of HIVTSQc at Weeks 4b, 24 and 44
timeFrame: Baseline and Weeks 4b, 24 and 44
Other outcomes:
measure: Number of Participants With Different Demographic Parameters for Inter-subject Variability
timeFrame: Upto Week 48
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Bakersfield
country: United States
facility: GSK Investigational Site
state: California
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Palm Springs
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: GSK Investigational Site
state: Florida
city: Fort Pierce
country: United States
facility: GSK Investigational Site
state: Florida
city: Sarasota
country: United States
facility: GSK Investigational Site
state: Florida
city: Vero Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Macon
country: United States
facility: GSK Investigational Site
state: Georgia
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Detroit
country: United States
facility: GSK Investigational Site
state: Michigan
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Buffalo
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Allentown
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Annandale
country: United States
facility: GSK Investigational Site
state: Virginia
city: Lynchburg
country: United States
facility: GSK Investigational Site
state: Virginia
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma De Bueno
country: Argentina
facility: GSK Investigational Site
city: Rosario
country: Argentina
facility: GSK Investigational Site
city: Darlinghurst
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Sydney
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Prahran
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Quebec City
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Regina
country: Canada
facility: GSK Investigational Site
state: Saskatchewan
city: Montpellier
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Saint-Denis Cedex
country: France
facility: GSK Investigational Site
city: Toulouse cedex 9
country: France
facility: GSK Investigational Site
city: Tourcoing Cedex
country: France
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Bonn
country: Germany
facility: GSK Investigational Site
city: Essen
country: Germany
facility: GSK Investigational Site
city: Frankfurt
country: Germany
facility: GSK Investigational Site
city: Frankfurt
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hannover
country: Germany
facility: GSK Investigational Site
city: Muenchen
country: Germany
facility: GSK Investigational Site
city: Brescia
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Daegu
country: Korea, Republic of
facility: GSK Investigational Site
city: Daejeon
country: Korea, Republic of
facility: GSK Investigational Site
city: Pusan
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Guadalajara
country: Mexico
facility: GSK Investigational Site
city: Ekaterinburg
country: Russian Federation
facility: GSK Investigational Site
city: Kazan
country: Russian Federation
facility: GSK Investigational Site
city: Kemerovo
country: Russian Federation
facility: GSK Investigational Site
city: Krasnodar
country: Russian Federation
facility: GSK Investigational Site
city: Lipetsk
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Orel
country: Russian Federation
facility: GSK Investigational Site
city: Saratov
country: Russian Federation
facility: GSK Investigational Site
city: Smolensk
country: Russian Federation
facility: GSK Investigational Site
city: St Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Toliyatti
country: Russian Federation
facility: GSK Investigational Site
city: Bloemfontein
country: South Africa
facility: GSK Investigational Site
city: Brandfort
country: South Africa
facility: GSK Investigational Site
city: Cape Town
country: South Africa
facility: GSK Investigational Site
city: Durban
country: South Africa
facility: GSK Investigational Site
city: Durban
country: South Africa
facility: GSK Investigational Site
city: Johannesburg
country: South Africa
facility: GSK Investigational Site
city: Middelburg
country: South Africa
facility: GSK Investigational Site
city: Pretorai
country: South Africa
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Cordoba
country: Spain
facility: GSK Investigational Site
city: Elche Alicante
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Malaga
country: Spain
facility: GSK Investigational Site
city: Santiago de Compostela
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Vigo Pontevedra
country: Spain
facility: GSK Investigational Site
city: Goteborg
country: Sweden
facility: GSK Investigational Site
city: Stockholm
country: Sweden
facility: GSK Investigational Site
city: Stockholm
country: Sweden
facility: GSK Investigational Site
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Swindells S, Lutz T, Van Zyl L, Porteiro N, Stoll M, Mitha E, Shon A, Benn P, Huang JO, Harrington CM, Hove K, Ford SL, Talarico CL, Chounta V, Crauwels H, Van Solingen-Ristea R, Vanveggel S, Margolis DA, Smith KY, Vandermeulen K, Spreen WR. Week 96 extension results of a Phase 3 study evaluating long-acting cabotegravir with rilpivirine for HIV-1 treatment. AIDS. 2022 Feb 1;36(2):185-194. doi: 10.1097/QAD.0000000000003025.
citation: Chounta V, Snedecor SJ, Wu S, Van de Velde N. Indirect comparison of 48-week efficacy and safety of long-acting cabotegravir and rilpivirine maintenance every 8 weeks with daily oral standard of care antiretroviral therapy in participants with virologically suppressed HIV-1-infection. BMC Infect Dis. 2022 May 4;22(1):428. doi: 10.1186/s12879-022-07243-3.
citation: Rizzardini G, Overton ET, Orkin C, Swindells S, Arasteh K, Gorgolas Hernandez-Mora M, Pokrovsky V, Girard PM, Oka S, Andrade-Villanueva JF, Richmond GJ, Baumgarten A, Masia M, Latiff G, Griffith S, Harrington CM, Hudson KJ, St Clair M, Talarico CL, Patel P, Cutrell A, Van Eygen V, D'Amico R, Mrus JM, Wu S, Ford SL, Chow K, Roberts J, Wills A, Walters N, Vanveggel S, Van Solingen-Ristea R, Crauwels H, Smith KY, Spreen WR, Margolis DA. Long-Acting Injectable Cabotegravir + Rilpivirine for HIV Maintenance Therapy: Week 48 Pooled Analysis of Phase 3 ATLAS and FLAIR Trials. J Acquir Immune Defic Syndr. 2020 Dec 1;85(4):498-506. doi: 10.1097/QAI.0000000000002466.
citation: Swindells S, Andrade-Villanueva JF, Richmond GJ, Rizzardini G, Baumgarten A, Masia M, Latiff G, Pokrovsky V, Bredeek F, Smith G, Cahn P, Kim YS, Ford SL, Talarico CL, Patel P, Chounta V, Crauwels H, Parys W, Vanveggel S, Mrus J, Huang J, Harrington CM, Hudson KJ, Margolis DA, Smith KY, Williams PE, Spreen WR. Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression. N Engl J Med. 2020 Mar 19;382(12):1112-1123. doi: 10.1056/NEJMoa1904398. Epub 2020 Mar 4.