Clinical trial NCT05896761: A Sub-study of Cabotegravir (CAB) and Rilpivirine (RPV) in Human Immunodeficiency Viruses (HIV)-Infected Participants
Official title: Sub-study to the A2M Study to Evaluate the Pharmacokinetics, Tolerability and Efficacy of Cabotegravir and Rilpivirine Long-Acting Injections Following Intramuscular Administration in the Vastus Lateralis Muscle (Thigh) in HIV-infected Adult Participants Who Have Received at Least Three Years of Gluteal Injections in the A2M Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Human Immunodeficiency Virus Type 1 (HIV-1)
Keywords: Cabotegravir
Efficacy
Human immunodeficiency virus
Pharmacokinetic
Rilpivirine
Safety
Tolerability
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
Collaborators: name: Janssen Research & Development, LLC
First posted: 2023-06-09
Enrollment: 118
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: 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 at Sub-Study Screening.

Inclusion criteria detailed for the ATLAS-2M main study apply to the sub-study:

* A female participant is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotropin \[hCG\] test) 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:

       i. Documented tubal ligation ii. Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion iii. Hysterectomy iv. 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 enrollment.
  2. 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, 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.

Exclusion Criteria:

Sub-study specific Exclusion Criteria:

* Participants with more than 1 plasma HIV-1 RNA measurement \>=50 copies/mL to \<200 copies/mL (virologic blip) within 24 weeks prior to sub-study Screening visit.
* Any Suspected Virologic Failure (HIV-RNA greater than \[\>\]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 \<200 cells per microliter are not exclusionary.
* Participants 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 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 enrollment 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 enrollment.
* Participants who, in the investigator's judgment, pose a significant suicide risk. Participant's recent history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk.
* 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 participant 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 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 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 with the exception of the use of low dose acetylsalicylic acid lesser than or equal to (\<=)325 mg or hereditary coagulation and platelet disorders such as hemophilia or Von Willebrand Disease.
* 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 creatine clearance \<50mL per minute per 1.73 square meter via Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) Method.
* Alanine aminotransferase (ALT) \>=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.

Primary outcomes:
measure: Concentration at End of Dosing Interval (Ctau) of CAB LA Following Administration of CAB LA + RPV LA Q8W
timeFrame: Weeks -8,-7,-4 and Pre-dose on Day 1(Pre-Thigh Gluteal Injection);2 Hours post-dose on Day 1,Pre-dose on Week 8,Weeks 1 and 4 post-dose(First Thigh Injection);2 Hours post-dose on Week 8 and Weeks 9, 12 post-dose,Pre-dose on Week 16(Last Thigh Injection)
measure: Concentration at End of Dosing Interval (Ctau) of RPV LA Following Administration of CAB LA + RPV LA Q8W
timeFrame: Weeks -8,-7,-4 and Pre-dose on Day 1(Pre-Thigh Gluteal Injection);2 Hours post-dose on Day 1,Pre-dose on Week 8,Weeks 1 and 4 post-dose(First Thigh Injection);2 Hours post-dose on Week 8 and Weeks 9, 12 post-dose,Pre-dose on Week 16(Last Thigh Injection)
measure: Maximum Plasma Concentration (Cmax) of CAB LA Following Administration of CAB LA + RPV LA Q8W
timeFrame: Weeks -8,-7,-4 and Pre-dose on Day 1(Pre-Thigh Gluteal Injection);2 Hours post-dose on Day 1,Pre-dose on Week 8,Weeks 1 and 4 post-dose(First Thigh Injection);2 Hours post-dose on Week 8 and Weeks 9, 12 post-dose,Pre-dose on Week 16(Last Thigh Injection)
measure: Maximum Plasma Concentration (Cmax) of RPV LA Following Administration of CAB LA + RPV LA Q8W
timeFrame: Weeks -8,-7,-4 and Pre-dose on Day 1(Pre-Thigh Gluteal Injection);2 Hours post-dose on Day 1,Pre-dose on Week 8,Weeks 1 and 4 post-dose(First Thigh Injection);2 Hours post-dose on Week 8 and Weeks 9, 12 post-dose,Pre-dose on Week 16(Last Thigh Injection)
measure: 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
timeFrame: Weeks -8,-7,-4 and Pre-dose on Day 1(Pre-Thigh Gluteal Injection);2 Hours post-dose on Day 1,Pre-dose on Week 8,Weeks 1 and 4 post-dose(First Thigh Injection);2 Hours post-dose on Week 8 and Weeks 9, 12 post-dose,Pre-dose on Week 16(Last Thigh Injection)
measure: 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
timeFrame: Weeks -8,-7,-4 and Pre-dose on Day 1(Pre-Thigh Gluteal Injection);2 Hours post-dose on Day 1,Pre-dose on Week 8,Weeks 1 and 4 post-dose(First Thigh Injection);2 Hours post-dose on Week 8 and Weeks 9, 12 post-dose,Pre-dose on Week 16(Last Thigh Injection)
measure: Concentration at End of Dosing Interval (Ctau) of CAB LA Following Administration of CAB LA + RPV LA Q4W
timeFrame: Weeks -4 and -3, Pre-dose on Day 1 (Pre-Thigh Gluteal Injection); 2 Hours post-dose on Day 1, Week 1 post-dose, Pre-dose on Week 4 (First Thigh Injection); 2 Hours post-dose on Week 12, Week 13 post-dose and Pre-dose on Week 16 (Last Thigh Injection)
measure: Concentration at End of Dosing Interval (Ctau) of RPV LA Following Administration of CAB LA + RPV LA Q4W
timeFrame: Weeks -4 and -3, Pre-dose on Day 1 (Pre-Thigh Gluteal Injection); 2 Hours post-dose on Day 1, Week 1 post-dose, Pre-dose on Week 4 (First Thigh Injection); 2 Hours post-dose on Week 12, Week 13 post-dose and Pre-dose on Week 16 (Last Thigh Injection)
measure: Maximum Plasma Concentration (Cmax) of CAB LA Following Administration of CAB LA + RPV LA Q4W
timeFrame: Weeks -4 and -3, Pre-dose on Day 1 (Pre-Thigh Gluteal Injection); 2 Hours post-dose on Day 1, Week 1 post-dose, Pre-dose on Week 4 (First Thigh Injection); 2 Hours post-dose on Week 12, Week 13 post-dose and Pre-dose on Week 16 (Last Thigh Injection)
measure: Maximum Plasma Concentration (Cmax) of RPV LA Following Administration of CAB LA + RPV LA Q4W
timeFrame: Weeks -4 and -3, Pre-dose on Day 1 (Pre-Thigh Gluteal Injection); 2 Hours post-dose on Day 1, Week 1 post-dose, Pre-dose on Week 4 (First Thigh Injection); 2 Hours post-dose on Week 12, Week 13 post-dose and Pre-dose on Week 16 (Last Thigh Injection)
measure: 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
timeFrame: Weeks -4 and -3, Pre-dose on Day 1 (Pre-Thigh Gluteal Injection); 2 Hours post-dose on Day 1, Week 1 post-dose, Pre-dose on Week 4 (First Thigh Injection); 2 Hours post-dose on Week 12, Week 13 post-dose and Pre-dose on Week 16 (Last Thigh Injection)
measure: 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
timeFrame: Weeks -4 and -3, Pre-dose on Day 1 (Pre-Thigh Gluteal Injection); 2 Hours post-dose on Day 1, Week 1 post-dose, Pre-dose on Week 4 (First Thigh Injection); 2 Hours post-dose on Week 12, Week 13 post-dose and Pre-dose on Week 16 (Last Thigh Injection)
Secondary outcomes:
measure: Number of Participants With Injection Site Reactions (ISRs) by Maximum Severity Grade - Thigh Injection Phase
timeFrame: Up to Week 16
measure: Number of Participants With Adverse Events of Special Interest (AESI) Based on Maximum Severity Grade- Thigh Injection Phase
timeFrame: Up to Week 16
measure: Number of Participants Who Discontinue Treatment Due to ISRs and AESIs-Thigh Injection Phase
timeFrame: Up to Week 16
measure: 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
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16
measure: 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
timeFrame: Baseline (Day 1) and at Weeks 4, 8, 12, 16
measure: Percentage of Participants With Protocol-defined Confirmed Virologic Failure (CVF)- Thigh Injection Phase
timeFrame: Up to Week 16
measure: Number of Participants With Treatment Emergent Genotypic Resistance - Thigh Injection Phase
timeFrame: Up to Week 16
measure: Number of Participants With Treatment Emergent Phenotypic Resistance - Thigh Injection Phase
timeFrame: Up to Week 16
measure: Number of Participants With Post-injection Pain Using Numerical Rating Scale (NRS) on Day 1-Thigh Injection Phase
timeFrame: Day 1
measure: 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
timeFrame: Week 8
measure: 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
timeFrame: Week 12
measure: Number of Participants With Post-injection Pain Using Numerical Rating Scale (NRS)- Return to Gluteal Injection Phase
timeFrame: Study Week 16
measure: HIV Treatment Satisfaction Questionnaire - Status Version (HIVTSQs) Total Score at Indicated Time Points-Thigh Injection Phase
timeFrame: Baseline (Day 1) and Week 16
measure: 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
timeFrame: Study Week 24
measure: 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
timeFrame: Study Week 20
measure: Change From Baseline in HIV Treatment Satisfaction Questionnaire - Status Version (HIVTSQs) Individual Item Score at Indicated Time Points- Thigh Injection Phase
timeFrame: Baseline (Day 1) and up to Week 16
measure: 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
timeFrame: Study Week 16 and Study Week 24
measure: 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
timeFrame: Study Week 16 and Study Week 20
measure: HIV Treatment Satisfaction Questionnaire - Change Version (HIVTSQc) Total Score at Indicated Time Points- Thigh Injection Phase
timeFrame: Up to Week 16
measure: HIV Treatment Satisfaction Questionnaire - Change Version (HIVTSQc) Individual Item Score at Indicated Time Points- Thigh Injection Phase
timeFrame: Up to Week 16
measure: Number of Participants With Their Treatment Preference as Assessed Using Preference Questionnaire for CAB LA + RPV LA Q8W Arm
timeFrame: Up to Study Week 24
measure: Number of Participants With Their Treatment Preference as Assessed Using Preference Questionnaire for CAB LA + RPV LA Q4W Arm
timeFrame: Up to Study Week 20
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: GSK Investigational Site
state: California
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: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Lynchburg
country: United States
facility: GSK Investigational Site
state: Virginia
city: Ciudad de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Rosario
country: Argentina
facility: GSK Investigational Site
state: Santa Fe
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Regina
country: Canada
facility: GSK Investigational Site
state: Saskatchewan
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Barcelona
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
country: Spain
facility: GSK Investigational Site
city: Göteborg
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: