Phase 3
N=94
Study to Assess the Effects of Cabotegravir (CAB) and Rilpivirine (RPV) Long-Acting (LA) Injections Following Sub-cutaneous (SC) Administration Compared With Intramuscular (IM) Administration in Adult Participants Living With Human Immunodeficiency Virus (HIV-1) Infection in the FLAIR Study
Human Immunodeficiency Virus Type 1 (HIV-1)
Bottom Line
View on ClinicalTrials.gov: NCT05896748 ↗Enrolled (actual)
94
Serious AEs
0.4%
Results posted
Nov 2024
Primary outcome: Primary: Concentrations at the End of the Dosing Interval (Ctau) of CAB LA 400 mg Following Administration CAB LA + RPV LA — 2.759; 2.670; 2.607; 2.632 microgram per milliliter (µg/mL)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Cabotegravir - Injectable Suspension (CAB LA) (Drug); Rilpivirine - Injectable Suspension (RPV LA) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- ViiV Healthcare
- Primary completion
- Sep 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Concentrations at the End of the Dosing Interval (Ctau) of CAB LA 400 mg Following Administration CAB LA + RPV LA |
2.759; 2.670; 2.607; 2.632; 2.797 | — |
| PRIMARY Ctau of RPV LA 600 mg Following Administration of CAB LA + RPV LA |
137.021; 138.611; 135.620; 128.590; 139.879 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) One Week Post Dose of CAB LA 400 mg Following Administration of CAB LA + RPV LA |
3.545; 3.316; 3.165; 3.215; 3.529 | — |
| PRIMARY Cmax One Week Post Dose of RPV LA 600 mg Following Administration of CAB LA + RPV LA |
162.287; 152.614; 148.051; 149.145; 154.659 | — |
| PRIMARY Area Under the Plasma Concentration-time Curve From 0 Through the End of Dosing Interval (AUC[0-tau]) of CAB LA 400 mg Following Administration of CAB LA + RPV LA |
2051.172; 1997.801; 1943.596; 1943.787; 2155.520 | — |
| PRIMARY AUC[0-tau] of RPV LA 600 mg Following Administration of CAB LA + RPV LA |
98003.488; 98801.696; 95743.414; 93248.069; 100006.767 | — |
| SECONDARY Number of Participants With Injection Site Reactions (ISRs) and by Maximum Severity - SC Injection Phase |
85; 43; 36; 6; 0; 0 | — |
| SECONDARY Number of Participants With Adverse Events of Special Interest (AESI) Based on Maximum Severity Grade - SC Injection Phase |
1; 0; 1; 0; 0; 0 | — |
| SECONDARY Number of Participants Who Discontinue Treatment Due to ISRs and AESIs - SC Injection Phase |
5; 0 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From the Last IM Gluteal Injection in Screening Phase to the End of the SC Injection Phase |
90; 0 | — |
| SECONDARY Change From Baseline in Chemistry Parameters Following Administration of SC Injection: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Creatine Phosphokinase |
21.6; 1.2; -0.4; -0.7; 62.3; -0.1 | — |
| SECONDARY Change From Baseline in Chemistry Parameters Following Administration of SC Injection: Creatinine, Total Bilirubin |
86.23; -1.84; -1.55; -0.35; 9.2; 0.5 | — |
| SECONDARY Change From Baseline in Chemistry Parameters Following Administration of SC Injection: Glucose, Potassium, Sodium, Blood Urea Nitrogen, Carbon Dioxide, Chloride, Phosphate |
5.14; -0.02; 4.19; 0.02; 0.03; -0.04 | — |
| SECONDARY Change From Baseline in Chemistry Parameter Following Administration of SC Injection: Albumin |
43.1; 0.4; 0.8; -0.1 | — |
| SECONDARY Change From Baseline in Chemistry Parameters Following Administration of SC Injection: Lipase |
29.4; 0.3; 5.6; 1.4 | — |
| SECONDARY Change From Baseline in Chemistry Parameters Following Administration of SC Injection: Creatinine Clearance |
93.9; 1.9; 1.8; 0.4 | — |
| SECONDARY Change From Baseline in Fasting Lipid Panels Following Administration of SC Injection: Total Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Triglycerides |
4.855; -0.073; 1.373; -0.050; 2.899; -0.040 | — |
| SECONDARY Change From Baseline in Hematology Parameters Following Administration of SC Injection: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelet Count |
0.048; 0.000; -0.003; -0.002; 0.193; 0.006 | — |
| SECONDARY Change From Baseline in Hematology Parameter Following Administration of SC Injection: Red Blood Cell (RBC) Count |
4.74; 0.03; 0.01; -0.04 | — |
| SECONDARY Change From Baseline in Hematology Parameter Following Administration of SC Injection: Hemoglobin |
142.9; 0.3; -0.9; -2.4 | — |
| SECONDARY Change From Baseline in Hematology Parameter Following Administration of SC Injection: Hematocrit |
0.4268; 0.0008; 0.0014; -0.0023 | — |
| SECONDARY Change From Baseline in Hematology Parameter Following Administration of SC Injection: Mean Corpuscular Volume |
90.2; -0.4; 0.2; 0.5 | — |
| SECONDARY Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<) 50 Copies Per Milliliter (c/mL) Using the Food and Drug Administration (FDA) Snapshot Algorithm - SC Injection Phase |
100; 100; 99; 90 | — |
| SECONDARY Percentage of Participants With Plasma HIV RNA Greater Than Equal to (>=) 50 c/mL as Per FDA Snapshot Algorithm - SC Injection Phase |
0; 0; 1.1; 2.2 | — |
| SECONDARY Percentage of Participants With Protocol Defined Confirmed Virologic Failure (CVF) of >=200 c/mL - SC Injection Phase |
— | — |
| SECONDARY Number of Participants With Treatment Emergent Phenotypic Resistance - SC Injection Phase |
— | — |
| SECONDARY Number of Participants With Treatment Emergent Genotypic Resistance - SC Injection Phase |
— | — |
| SECONDARY Number of Participants With Post-injection Pain Assessment Using Numeric Rating Scale (NRS) on Week-3 - Screening/IM Gluteal Injection Phase |
37; 27; 21; 16; 11; 18 | — |
| SECONDARY Number of Participants With Post-injection Pain Assessment Using Numeric Rating Scale (NRS) on Week 1 - SC Injection Phase |
16; 22; 13; 19; 16; 10 | — |
| SECONDARY Number of Participants With Post-injection Pain Assessment Using NRS on Week 9- SC Injection Phase |
21; 19; 9; 11; 19; 15 | — |
| SECONDARY Number of Participants With Post-injection Pain Assessment Using NRS on Week 13- Return to IM Gluteal Injection Phase |
40; 41; 21; 13; 10; 12 | — |
| SECONDARY HIV Treatment Satisfaction Questionnaire - Status Version (HIVTSQs) Total Score -Screening/IM Gluteal Injection Phase |
62.15 | — |
| SECONDARY HIVTSQs Total Score -SC Injection Phase |
51.99 | — |
| SECONDARY HIVTSQs Total Score -Return to IM Gluteal Injection Phase |
62.71 | — |
| SECONDARY Change From Baseline in HIVTSQs Individual Item Scores at Indicated Time Points -SC Injection Phase |
-1.2; -0.2; -1.5; -1.1; -1.2; -0.8 | — |
| SECONDARY Change From Baseline in HIVTSQs Individual Item Scores at Indicated Time Points - Return to IM Gluteal Injection Phase |
0.1; -0.1; 0.1; 0.0; 0.0; 0.0 | — |
| SECONDARY Change From Study Week 9 to Study Week 17 in HIVTSQs Individual Item Scores at Indicated Time Points - Return to IM Gluteal Injection Phase |
1.3; 0.2; 1.6; 1.1; 1.2; 0.8 | — |
| SECONDARY HIV Treatment Satisfaction Questionnaire - Change Version (HIVTSQc) Individual Item Score at Indicated Time Points -SC Injection Phase |
0.7; 1.8; 0.5; 1.2; 1.0; 1.3 | — |
| SECONDARY HIVTSQc Total Score at Indicated Time Points -SC Injection Phase |
13.4 | — |
| SECONDARY Perception of Injection (PIN) Questionnaire in Domain Scores and Individual Item Scores- Screening/IM Gluteal Injection Phase |
1.44; 1.53; 1.51; 1.71 | — |
| SECONDARY PIN Questionnaire in Domain Scores and Individual Item Scores at Indicated Time Points - SC Injection Phase |
2.23; 1.95; 2.10; 1.93; 2.60; 2.28 | — |
| SECONDARY PIN Questionnaire in Domain Scores and Individual Item Scores - Return to IM Gluteal Injection Phase |
1.23; 1.28; 1.32; 1.46 | — |
| SECONDARY Change From Baseline to the PIN Questionnaire in Domain Scores and Individual Item Scores at Indicated Time Points - SC Injection Phase |
0.79; 0.41; 0.70; 0.41; 1.09; 0.58 | — |
| SECONDARY Change From Baseline to the PIN Questionnaire in Domain Scores and Individual Item Scores at Indicated Time Points - Return to IM Gluteal Injection Phase |
-0.17; -0.24; -0.12; -0.22 | — |
| SECONDARY Number of Participants With Their Treatment Preference Assessed Using Preference Questionnaire on Week 9 - SC Injection Phase |
50; 29; 6 | — |
| SECONDARY Number of Participants With Their Treatment Preference Assessed Using Preference Questionnaire on Week 17 - Return to IM Gluteal Injection Phase |
61; 21; 5 | — |
Summary
This study will assess the pharmacokinetics, safety, tolerability, maintenance of virological suppression and patient reported outcomes for participants receiving CAB and RPV LA injections following SC administration in the anterior abdominal wall SC tissue compared with IM administration in the gluteus medius muscle in adult participants living with HIV-1 infection in the FLAIR study (NCT02938520).
Eligibility Criteria
Inclusion Criteria
- Capable of giving signed informed consent (FLAIR and Sub-study specific informed consent)
- Eligible participants must have been on CAB LA + RPV LA regimen for a minimum of 12 months while on the FLAIR study. Any disruptions in dosing during FLAIR must be discussed with the Medical Monitor for a final determination of eligibility into the sub-study.
- Plasma HIV-1 RNA =1000 cubic (c)/mL
- Antiretroviral-naive (less than or equal to ( 3.25 is exclusionary;
- Fib-4 scores 1.45 - 3.25 requires Medical Monitor consultation. Fibrosis 4 Score Formula: (Age * AST)/ (Platelets * [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 (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.
- 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).
- 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 Integrase inhibitors from historical resistance test results.
- Participants who are human leukocyte antigen (HLA)-B*5701 positive and are unable to use an NRTI backbone that does not contain abacavir (participants who are HL
Data sourced from ClinicalTrials.gov (NCT05896748). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.