Clinical trial NCT02938520: Study to Evaluate the Efficacy, Safety, and Tolerability of Long-acting Intramuscular Cabotegravir and Rilpivirine for Maintenance of Virologic Suppression Following Switch From an Integrase Inhibitor in HIV-1 Infected Therapy Naive Participants
Official title: A Phase III, Randomized, Multicenter, Parallel-group, Open-Label Study Evaluating the Efficacy, Safety, and Tolerability of Long-Acting Intramuscular Cabotegravir and Rilpivirine for Maintenance of Virologic Suppression Following Switch From an Integrase Inhibitor Single Tablet Regimen in HIV-1 Infected Antiretroviral Therapy Naive Adult Participants
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: HIV Infections
Keywords: Antiretroviral agent
Maintenance
rilpivirine
dolutegravir
TMC278
Triumeq
non-nucleoside reverse transcriptase inhibitor
once monthly, every 4 weeks, once daily
GSK1265744
CAB
Tivicay
Long-Acting Intramuscular rilpivirine
lamivudine
integrase inhibitor
Long-Acting Intramuscular Cabotegravir
ART naïve
cabotegravir
abacavir
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
Collaborators: name: Janssen Pharmaceuticals
name: GlaxoSmithKline
First posted: 2016-10-19
Enrollment: 631
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 First Long-Acting Injectable Regimen (FLAIR) study is being conducted to establish if human immunodeficiency virus type-1 (HIV-1) infected adult participants whose virus is virologically suppressed on an integrase inhibitor single tablet regimen (INI STR) will remain suppressed after switching to a two-drug intramuscular (IM) long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In this study, the INI STR will be limited to abacavir/dolutegravir/lamivudine (ABC/DTG/3TC). FLAIR is a Phase 3, multi-phase, randomized, open label, active-controlled, multicenter, parallel-group, non-inferiority study in HIV-1, anti-retroviral therapy (ART)-naïve adult participants. This study is designed to demonstrate the non-inferior antiviral activity of switching to a two drug CAB LA 400 mg + RPV LA 600 mg regimen every 4 weeks (Q4W: monthly) compared to remaining on ABC/DTG/3TC over 48 weeks (4 weeks oral CAB + RPV, 44 weeks LA therapy). Participants who are HLA-B\*5701 positive at Screening may enroll into the study and receive DTG plus a non-abacavir containing dual nucleoside reverse transcriptase inhibitor (NRTI) regimen. Eligible participants will enroll into the Induction Phase of the study and receive ABC/DTG/3TC for 20 weeks (Week \[-20\] to Day 1). Participants who have an HIV 1 ribose nucleic acid (RNA) \<50 copies per milliliter (c/mL) at Week (-4) will be randomized (1:1) into the Maintenance Phase at Day 1 to either continue ABC/DTG/3TC or to discontinue ABC/DTG/3TC and begin oral therapy with CAB 30 mg + RPV 25 mg once daily for approximately 4 Weeks, followed by monthly CAB LA + RPV LA injections from visit Week 4b until study completion or withdrawal. Participants who successfully complete Week 100 (without meeting study defined withdrawal criteria and who remain virologically suppressed through Week 96: HIV-1 RNA \<50 c/mL) will be given the option to switch to the LA arm in the Extension Phase (using an optional oral lead-in with CAB + RPV) or be withdrawn from the study. Participants will continue to receive injections every 4 weeks during the Extension Phase until CAB LA and RPV LA are either locally approved and commercially available, the participant no longer derives clinical benefit, the participant meets a protocol-defined reason for discontinuation, or until development of either CAB LA or RPV LA is terminated.


Eligibility criteria: Inclusion Criteria: - HIV-1 infected, ART-naive men or women aged 18 years or greater at the time of signing the informed consent. - HIV-1 infection as documented by Screening plasma HIV-1 RNA \>=1000 c/mL; - Antiretroviral-naive (\<=10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection). Any previous exposure to an HIV integrase inhibitor or non-nucleoside reverse transcriptase inhibitor will be exclusionary. - Female Participants: A female participant is eligible to participate if she is not pregnant at Screening and first day of Induction Phase (as confirmed by a negative serum human chorionic gonadotrophin \[hCG\] test), not lactating, and at least one of the following conditions applies: Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation; Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; Hysterectomy; Documented Bilateral Oophorectomy; Postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication, throughout the study, and for at least 30 days after discontinuation of all oral study medications and for at least 52 weeks after discontinuation of CAB LA and RPV LA. The investigator is responsible for ensuring that participants understand how to properly use these methods of contraception. All participants in the study should be counseled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g., male condom) and on the risk of HIV transmission to an uninfected partner. - Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. - In France, a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria: - Women who are pregnant, breastfeeding, or plan to become pregnant or breastfeed during the study. - Any evidence at Screening of an active Centers for Disease and Prevention Control (CDC) Stage 3 disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy or historic or current cluster of differentiation4+ (CD4+) cell count \<200 cells/ cubic millimeter (mm\^3) are not exclusionary. - Participants with known moderate to severe hepatic impairment. - Any pre-existing physical or mental condition (including substance abuse disorder) which, in the opinion of the Investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant. - Participants determined by the Investigator to have a high risk of seizures, including participants with an unstable or poorly controlled seizure disorder. A participant with a prior history of seizure may be considered for enrolment if the Investigator believes the risk of seizure recurrence is low. All cases of prior seizure history should be discussed with the Medical Monitor prior to enrolment. - Participant who, in the investigator's judgment, poses a significant suicide risk. Participant's recent history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk. - The participant has a tattoo or other dermatological condition overlying the gluteus region which may interfere with interpretation of injection site reactions. - Evidence of Hepatitis B virus (HBV) infection based on the results of testing at Screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti HBc), Hepatitis B surface antibody (anti-HBs) and HBV dioxyribose nucleic acid (DNA) as follows: Participants positive for HBsAg are excluded; Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded. Note: Participants positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded. - Asymptomatic individuals with chronic hepatitis C virus (HCV) infection will not be excluded, however Investigators must carefully assess if therapy specific for HCV infection is required; participants who are anticipated to require HCV treatment prior to Week 48 of the Maintenance Phase must be excluded. HCV treatment on study may be permitted post Week 48, following consultation with the Medical Monitor. Participants with HCV co-infection will be allowed entry into Phase 3 studies if: Liver enzymes meet entry criteria; HCV Disease has undergone appropriate work-up, HCV is not advanced, and will not require treatment prior to the Week 48 visit. Additional information (where available) on participants with HCV co-infection at screening should include results from any liver biopsy, fibroscan, ultrasound, or other fibrosis evaluation, history of cirrhosis or other decompensated liver disease, prior treatment, and timing/plan for HCV treatment. In the event that recent biopsy or imaging data is not available or is inconclusive, the Fib-4 score will be used to verify eligibility. A Fib-4 score \> 3.25 is exclusionary; Fib-4 scores 1.45 - 3.25 requires Medical Monitor consultation. Fibrosis 4 Score Formula: (Age x AST)/(Platelets x \[square root of ALT\]). - Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment). - History of liver cirrhosis with or without hepatitis viral co-infection. - Ongoing or clinically relevant pancreatitis. - All participants will be screened for syphilis (rapid plasma reagin \[RPR\]). Participants with untreated syphilis infection, defined as a positive RPR without clear documentation of treatment, are excluded. Participants with a positive RPR test who have not been treated may be rescreened at least 30 days after completion of antibiotic treatment for syphilis. - Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the study Medical Monitor for inclusion of the participant prior to enrollment. - Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the drug or render the participant unable to receive study medication. - History or presence of allergy or intolerance to the study drugs or their components or drugs of their class. In addition, if heparin is used during pharmacokinetic sampling (PK) sampling, participants with a history of sensitivity to heparin or heparin-induced thrombocytopenia must not be enrolled. - Current or anticipated need for chronic anti-coagulation. - Alanine aminotransferase (ALT) \>=3 times upper limit normal (ULN). - Clinically significant cardiovascular disease, as defined by history/evidence of congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PTCA) or any clinically significant cardiac disease. - Exposure to an experimental drug and/or experimental vaccine within 28 days or 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of investigational product (IP). - Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; tuberculosis (TB) therapy, with the exception of treatment of latent TB with isoniazid; Immunomodulators that alter immune responses (such as chronic systemic corticosteroids, interleukins, or interferons). Note: Participants using short-term (e.g. =\<21 day) systemic corticosteroid treatment, topical, inhaled or intranasal corticosteroids are eligible for enrollment. - Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening. - Treatment with any agent, except recognized ART as allowed above, with documented activity against HIV-1 within 28 days of the first dose of IP. - Use of medications which are associated with Torsades de Pointes - Any evidence of primary resistance to non-nuclease reverse transcriptase inhibitors (NNRTIs) (except for K103N which is allowed), or any known resistance to INIs from historical resistance test results. Note: re-tests of Screening genotypes are allowed only at the discretion of the study virologist. - Participants who are HLA-B\*5701 positive and are unable to use an nuclease reverse transcriptase inhibitors (NRTI) backbone that does not contain abacavir (participants who are HLA-B\*5701 positive may be enrolled if they use a NRTI backbone that does not contain abacavir; HLA-B\*5701 positive participants may be excluded from the study if local provision of an alternate NRTI backbone is not possible). - Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the Screening Phase to verify a result. - Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the participant's participation in the study of an investigational compound. - Participant has estimated creatinine clearance \<50 mL/min/1.73m\^2 via the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. - Participants who are currently participating in or anticipate to be selected for any other interventional study.

Primary outcomes:
measure: Percentage 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: Percentage 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) During the Maintenance Phase
timeFrame: Week 48
measure: Absolute Values for Plasma HIV-1 RNA at Week 48
timeFrame: Week 48
measure: Change From Baseline Values for Plasma HIV-1 RNA at Week 48
timeFrame: Baseline (Day 1) and at 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: Day 1 up to an average of 59 weeks
measure: Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to an average of 59 Weeks
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: Basophils, 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 Over Time Including Week 48: 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 Over Time Including Week 48: 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 Over Time Including Week 48: 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 Over Time Including Week 48: Hematocrit
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: Absolute Values for Fasting Lipid Panel Overtime Including Week 48
timeFrame: Baseline (Day 1) and at Week 48
measure: Number of Participants With Abnormal Urinalysis Parameter 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 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: 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 and Glucose Overtime 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: Week 48
measure: Number of Participants With Genotypic Resistance Through Week 48
timeFrame: Week 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, 41, 2 hours post-dose at Weeks 4 and 48
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, 41, 2 hours post-dose at Weeks 4 and 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: 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: Change From Week 5 in Dimension Scores Using Perception of Injection Questionnaire (PIN)-Last Observation Carried Forward (LOCF)
timeFrame: Weeks 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
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 HIVTSQc at Week 48
timeFrame: Week 48
measure: Change From Baseline in Individual Item Scores of HIVTSQs at Weeks 4b, 24 and 44
timeFrame: Baseline and at Weeks 4b, 24 and 44
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 Weeks 5, 40 and 41 Using Numeric Rating Scale (NRS) Within CAB LA+RPV LA Arm
timeFrame: Weeks 4b, 5, 40 and 41
Other outcomes:
measure: Number of Participants With Different Demographic Parameters for Inter-subject Variability
timeFrame: Up to Week 48
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
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: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Aurora
country: United States
facility: GSK Investigational Site
state: Colorado
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: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Augusta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Macon
country: United States
facility: GSK Investigational Site
state: Georgia
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Camden
country: United States
facility: GSK Investigational Site
state: New Jersey
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Providence
country: United States
facility: GSK Investigational Site
state: Rhode Island
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Bellaire
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Longview
country: United States
facility: GSK Investigational Site
state: Texas
city: Lynchburg
country: United States
facility: GSK Investigational Site
state: Virginia
city: Vancouver
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
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: Bobigny cedex
country: France
facility: GSK Investigational Site
city: Lyon
country: France
facility: GSK Investigational Site
city: Marseille
country: France
facility: GSK Investigational Site
city: Paris Cedex 20
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: 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: Muenchen
country: Germany
facility: GSK Investigational Site
city: Brescia
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Monza MB
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Groningen
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Utrecht
country: Netherlands
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: Pretoria
country: South Africa
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Bilbao
country: Spain
facility: GSK Investigational Site
city: El Ferrol
country: Spain
facility: GSK Investigational Site
city: Elche Alicante
country: Spain
facility: GSK Investigational Site
city: Granada
country: Spain
facility: GSK Investigational Site
city: La CoruNa
country: Spain
facility: GSK Investigational Site
city: La Laguna Santa Cruz
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: Murcia
country: Spain
facility: GSK Investigational Site
city: Murcia
country: Spain
facility: GSK Investigational Site
city: Palma de Mallorca
country: Spain
facility: GSK Investigational Site
city: Palma de Mallorca
country: Spain
facility: GSK Investigational Site
city: San SebastiAn De Los Rey
country: Spain
facility: GSK Investigational Site
city: Santa Cruz de Tenerife
country: Spain
facility: GSK Investigational Site
city: Santander
country: Spain
facility: GSK Investigational Site
city: Birmingham
country: United Kingdom
facility: GSK Investigational Site
city: Coventry
country: United Kingdom
facility: GSK Investigational Site
city: Leeds Yorkshire
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Orkin C, Arasteh K, Gorgolas Hernandez-Mora M, Pokrovsky V, Overton ET, Girard PM, Oka S, Walmsley S, Bettacchi C, Brinson C, Philibert P, Lombaard J, St Clair M, Crauwels H, Ford SL, Patel P, Chounta V, D'Amico R, Vanveggel S, Dorey D, Cutrell A, Griffith S, Margolis DA, Williams PE, Parys W, Smith KY, Spreen WR. Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection. N Engl J Med. 2020 Mar 19;382(12):1124-1135. doi: 10.1056/NEJMoa1909512. Epub 2020 Mar 4.
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: Jeffrey JL, St Clair M, Wang P, Wang C, Li Z, Beloor J, Talarico C, Fridell R, Krystal M, White CT, Griffith S, D'Amico R, Smith K, Van Eygen V, Vingerhoets J, Vandermeulen K, Spreen W, van Lunzen J. Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Antimicrob Agents Chemother. 2022 Mar 15;66(3):e0170221. doi: 10.1128/AAC.01702-21. Epub 2022 Jan 3.
citation: Orkin C, Bernal Morell E, Tan DHS, Katner H, Stellbrink HJ, Belonosova E, DeMoor R, Griffith S, Thiagarajah S, Van Solingen-Ristea R, Ford SL, Crauwels H, Patel P, Cutrell A, Smith KY, Vandermeulen K, Birmingham E, St Clair M, Spreen WR, D'Amico R. Initiation of long-acting cabotegravir plus rilpivirine as direct-to-injection or with an oral lead-in in adults with HIV-1 infection: week 124 results of the open-label phase 3 FLAIR study. Lancet HIV. 2021 Nov;8(11):e668-e678. doi: 10.1016/S2352-3018(21)00184-3. Epub 2021 Oct 14.
citation: Orkin C, Oka S, Philibert P, Brinson C, Bassa A, Gusev D, Degen O, Garcia JG, Morell EB, Tan DHS, D'Amico R, Dorey D, Griffith S, Thiagarajah S, St Clair M, Van Solingen-Ristea R, Crauwels H, Ford SL, Patel P, Chounta V, Vanveggel S, Cutrell A, Van Eygen V, Vandermeulen K, Margolis DA, Smith KY, Spreen WR. Long-acting cabotegravir plus rilpivirine for treatment in adults with HIV-1 infection: 96-week results of the randomised, open-label, phase 3 FLAIR study. Lancet HIV. 2021 Apr;8(4):e185-e196. doi: 10.1016/S2352-3018(20)30340-4.
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.