Phase 3
N=118
A Sub-study of Cabotegravir (CAB) and Rilpivirine (RPV) in Human Immunodeficiency Viruses (HIV)-Infected Participants
Human Immunodeficiency Virus Type 1 (HIV-1)
Bottom Line
View on ClinicalTrials.gov: NCT05896761 ↗Enrolled (actual)
118
Serious AEs
0.4%
Results posted
Sep 2023
Primary outcome: Primary: Concentration at End of Dosing Interval (Ctau) of CAB LA Following Administration of CAB LA + RPV LA Q8W — 1.67; 1.61; 1.81 Micrograms per milliliter
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Cabotegravir Injectable Suspension (Drug); Rilpivirine Injectable Suspension (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- ViiV Healthcare
- Primary completion
- Aug 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Concentration at End of Dosing Interval (Ctau) of CAB LA Following Administration of CAB LA + RPV LA Q8W |
1.67; 1.61; 1.81 | — |
| PRIMARY Concentration at End of Dosing Interval (Ctau) of RPV LA Following Administration of CAB LA + RPV LA Q8W |
103; 117; 104 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of CAB LA Following Administration of CAB LA + RPV LA Q8W |
4.52; 3.70; 3.36 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of RPV LA Following Administration of CAB LA + RPV LA Q8W |
184; 172; 146 | — |
| PRIMARY Area Under the Concentration Curve From 0 Hours to the Time of Next Dosing (AUC [0-tau]) of CAB LA Following Administration of CAB LA + RPV LA Q8W |
4038; 3384; 3344 | — |
| PRIMARY Area Under the Concentration Curve From 0 Hours to the Time of Next Dosing (AUC [0-tau]) of RPV LA Following Administration of CAB LA + RPV LA Q8W |
179483; 190641; 162046 | — |
| PRIMARY Concentration at End of Dosing Interval (Ctau) of CAB LA Following Administration of CAB LA + RPV LA Q4W |
3.34; 3.00; 2.94 | — |
| PRIMARY Concentration at End of Dosing Interval (Ctau) of RPV LA Following Administration of CAB LA + RPV LA Q4W |
170; 171; 162 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of CAB LA Following Administration of CAB LA + RPV LA Q4W |
4.65; 4.09; 3.95 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of RPV LA Following Administration of CAB LA + RPV LA Q4W |
210; 205; 197 | — |
| PRIMARY Area Under the Concentration Curve From 0 Hours to the Time of Next Dosing (AUC [0-tau]) of CAB LA Following Administration of CAB LA + RPV LA Q4W |
2558; 2379; 2275 | — |
| PRIMARY Area Under the Concentration Curve From 0 Hours to the Time of Next Dosing (AUC [0-tau]) of RPV LA Following Administration of CAB LA + RPV LA Q4W |
120963; 123197; 115202 | — |
| SECONDARY Number of Participants With Injection Site Reactions (ISRs) by Maximum Severity Grade - Thigh Injection Phase |
18; 27; 16; 12; 4; 6 | — |
| SECONDARY Number of Participants With Adverse Events of Special Interest (AESI) Based on Maximum Severity Grade- Thigh Injection Phase |
18; 27; 16; 12; 4; 6 | — |
| SECONDARY Number of Participants Who Discontinue Treatment Due to ISRs and AESIs-Thigh Injection Phase |
1; 0; 1; 0 | — |
| SECONDARY Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (Copies/mL) Using the Food and Drug (FDA) Snapshot Algorithm-Thigh Injection Phase |
100; 98; 100; 98; 96; 97 | — |
| SECONDARY Percentage of Participants With Plasma HIV RNA Greater Than or Equal to (>=)50 Copies/mL Over Time as Per the FDA Snapshot Algorithm- Thigh Injection Phase |
0; 1.6; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Protocol-defined Confirmed Virologic Failure (CVF)- Thigh Injection Phase |
0; 0 | — |
| SECONDARY Number of Participants With Treatment Emergent Genotypic Resistance - Thigh Injection Phase |
— | — |
| SECONDARY Number of Participants With Treatment Emergent Phenotypic Resistance - Thigh Injection Phase |
— | — |
| SECONDARY Number of Participants With Post-injection Pain Using Numerical Rating Scale (NRS) on Day 1-Thigh Injection Phase |
14; 21; 13; 16; 7; 6 | — |
| SECONDARY Number of Participants With Post-injection Pain Using Numerical Rating Scale (NRS) for CAB LA + RPV LA Q8W Arm on Week 8- Thigh Injection Phase |
15; 11; 9; 5; 1; 3 | — |
| SECONDARY Number of Participants With Post-injection Pain Using Numerical Rating Scale (NRS) for CAB LA + RPV LA Q4W Arm on Week 12- Thigh Injection Phase |
20; 12; 7; 4; 9; 4 | — |
| SECONDARY Number of Participants With Post-injection Pain Using Numerical Rating Scale (NRS)- Return to Gluteal Injection Phase |
14; 22; 8; 11; 10; 6 | — |
| SECONDARY HIV Treatment Satisfaction Questionnaire - Status Version (HIVTSQs) Total Score at Indicated Time Points-Thigh Injection Phase |
63.85; 64.03; 61.69; 61.74 | — |
| SECONDARY HIV Treatment Satisfaction Questionnaire - Status Version (HIVTSQs) Total Score at Indicated Time Points for CAB LA + RPV LA Q8W Arm -Return to Gluteal Injection Phase |
63.78 | — |
| SECONDARY HIV Treatment Satisfaction Questionnaire - Status Version (HIVTSQs) Total Score at Indicated Time Points for CAB LA + RPV LA Q4W Arm -Return to Gluteal Injection Phase |
63.25 | — |
| SECONDARY Change From Baseline in HIV Treatment Satisfaction Questionnaire - Status Version (HIVTSQs) Individual Item Score at Indicated Time Points- Thigh Injection Phase |
-0.3; -0.3; -0.1; 0.0; -0.7; -0.2 | — |
| SECONDARY Change From Study Week 16 to Study Week 24 in HIV Treatment Satisfaction Questionnaire - Status Version (HIVTSQs) Individual Item Score at Indicated Time Points for CAB LA + RPV LA Q8W Arm- Return to Gluteal Injection |
0.3; 0.0; 0.5; 0.2; 0.1; 0.3 | — |
| SECONDARY Change From Study Week 16 to Study Week 20 in HIV Treatment Satisfaction Questionnaire - Status Version (HIVTSQs) Individual Item Score at Indicated Time Points for CAB LA + RPV LA Q4W Arm- Return to Gluteal Injection Phase |
0.2; 0.1; 0.3; 0.1; 0.1; 0.1 | — |
| SECONDARY HIV Treatment Satisfaction Questionnaire - Change Version (HIVTSQc) Total Score at Indicated Time Points- Thigh Injection Phase |
17.8; 19.7 | — |
| SECONDARY HIV Treatment Satisfaction Questionnaire - Change Version (HIVTSQc) Individual Item Score at Indicated Time Points- Thigh Injection Phase |
1.5; 1.7; 1.8; 1.9; 1.3; 1.5 | — |
| SECONDARY Number of Participants With Their Treatment Preference as Assessed Using Preference Questionnaire for CAB LA + RPV LA Q8W Arm |
29; 17; 5 | — |
| SECONDARY Number of Participants With Their Treatment Preference as Assessed Using Preference Questionnaire for CAB LA + RPV LA Q4W Arm |
39; 17; 5 | — |
Summary
This sub-study will assess the pharmacokinetics (PK), safety, tolerability, virologic efficacy and health outcomes of CAB (GSK1265744) and RPV long acting (LA) in HIV-infected adult participants currently enrolled in the Antiretroviral Therapy as Long Acting Suppression every 2 Months (ATLAS2M [A2M]) study (NCT03299049).
Eligibility Criteria
Inclusion Criteria
Sub-study specific Inclusion Criteria:
- Capable of giving sub-study specific informed consent.
- Eligible participants must have been on CAB LA + RPV LA regimen for a minimum of 152 weeks while on the ATLAS2-M study. Any disruptions in dosing during ATLAS2-M must be discussed with the Medical Monitor for a final determination of eligibility into the sub-study.
- Plasma HIV-1 RNA =50 copies/mL to ]200 copies/mL as defined in during ATLAS-2M study.
- Participants planning to require oral bridging during participation in the ATLAS-2M sub-study.
- The participant has a tattoo or any dermatological condition overlying the thigh region which may interfere with interpretation of injection site reactions.
- Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to receive study medication.
Exclusion criteria detailed for the ATLAS-2M main study apply to the sub-study:
- Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the study.
- Any evidence of a current Center for Disease Control and Prevention (CDC) Stage 3 disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy, and Cluster of Differentiation 4 positive (CD4+) counts =3 × upper limit of normal (ULN) at Screening.
- Exposure to an experimental drug (with the exception of those in the ATLAS-2M study including CAB, CAB LA, and RPV, RPV LA) 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:
i. radiation therapy; ii. cytotoxic chemotherapeutic agents; iii. tuberculosis therapy with the exception of isoniazid (isonicotinylhydrazid [INH]); iv. anti-coagulation agents; v. 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.
- Use of medications which are associated with Torsade de Pointes.
- Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication.
Data sourced from ClinicalTrials.gov (NCT05896761). 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.