Phase 2b, Open-label, Multicenter, Rollover Study to Assess Antiviral Activity and Safety of Long-acting (LA) Cabotegravir (CAB) Plus LA Rilpivirine (RPV), Administered Every 2 Months (Q2M), in Human Immunodeficiency Virus (HIV)-Positive Participants From the LATTE Study

NCT03639311 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 209035
• Study Type: interventional
• Target: 97
• Locations: 2 countries
• Sites: 30

Brief Summary

This study (POLAR), is designed to assess the antiviral activity and safety of CAB LA plus RPV LA, administered Q2M, in approximately 100 adult HIV-1 infected, antiretroviral therapy (ART) experienced participants. Participants will rollover from the NCT01641809 (LATTE) study, who have completed minimum duration of Week 312 and with demonstrated HIV-1 ribonucleic acid (RNA) suppression (less than \[\<\]50 copies (c) per milliliter \[mL\]), while receiving a two-drug regimen consisting of once-daily oral CAB at 30 milligram (mg) plus RPV at 25 mg. The participants will be offered the option to switch to the LA, intramuscular injections of CAB LA plus RPV LA, Q2M or the oral fixed dose combination (FDC) of dolutegravir (DTG) plus RPV, for the continued maintenance of HIV-1 RNA suppression, known as the Maintenance Phase (From Day 1 to Commercial Approval). Duration of study will vary from country to country, until regimen receives regulatory approval and becomes commercially available. The study plans to enroll approximately 100 participants. Any participant who receives at least one dose of CAB LA and/or RPV LA and discontinues the CAB LA plus RPV LA regimen for any reason will enter a 52-week Long-Term Follow-Up (LTFU) phase. Those participants must remain on suppressive highly active antiretroviral therapy (HAART) for at least 52 weeks after the last dose of CAB LA and or RPV LA.

Conditions

HIV Infections

Keywords

HIV; Antiretroviral therapy; Maintenance; Long acting; LATTE

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With HIV-ribonucleic Acid (RNA) >=50 Copies Per Milliliter (c/mL) as Per Food and Drug Administration (FDA) Snapshot Algorithm at Month 12 [Maintenance Phase]

  Percentage of participants with HIV-1 RNA \>=50 c/mL as per FDA snapshot algorithm at Month 12 was assessed to demonstrate the antiviral activity of CAB LA+RPV LA Q2M and DTG + RPV regimen in HIV-1 infected antiretroviral therapy (ART) experienced participants. The HIV-1 RNA \>=50 c/mL per Snapshot algorithm was determined by the last on-treatment HIV-1 RNA measurement within the 12 months analysis visit window.

  At Month 12 [Maintenance Phase]

Secondary Outcomes (61)

• Percentage of Participants With HIV-RNA <50 c/mL as Per FDA Snapshot Algorithm at Month 12 [Maintenance Phase]

  At Month 12 [Maintenance Phase]

• Number of Participants With Protocol-defined Confirmed Virologic Failure up to End of Maintenance Phase

  Up to End of Maintenance Phase (up to Month 52 for CAB LA+RPV LA Q2M group, up to Month 12 for DTG+RPV group)

• Percentage of Participants With HIV-RNA >=50 c/mL as Per FDA Snapshot Algorithm Over Time for CAB LA + RPV LA Q2M Arm up to Month 12 [Maintenance Phase]

  At Baseline (Day 1) and at Months 2, 4, 6, 8, 10 and 12 [Maintenance Phase]

• Percentage of Participants With HIV-RNA >=50 c/mL as Per FDA Snapshot Algorithm Over Time for DTG + RPV up to Month 12 [Maintenance Phase]

  At Baseline (Day 1) and at Months 3, 6, 9 and 12 [Maintenance Phase]

• Absolute Values for HIV-1 RNA of CAB LA + RPV LA Q2M Arm up to End of LTFU Phase

  From Baseline (Day 1) up to End of LTFU Phase (approximately up to 12 months after exiting the Maintenance Phase)

Other Outcomes (2)

• Plasma Trough Concentration (Ctrough) for CAB LA

  Pre-dose (Day 1) and Month 12 [Maintenance Phase]

• Ctrough for RPV LA

  Pre-dose (Day 1) and Month 12 [Maintenance Phase]

Study Arms (3)

CAB LA + RPV LA Q2M

EXPERIMENTAL

Eligible participants from LAI116482 (NCT01641809 \[LATTE\]) study who were administered oral CAB 30 milligrams (mg) plus RPV 25 mg and who successfully completed Week 300 received their first dose CAB LA (600 mg) plus RPV LA (900 mg) injections within 2 hours of the final oral dose of LATTE given on the same day. The second loading injections were administered 1 month after initial loading dose, with subsequent injections (CAB LA 600 mg + RPV LA 900 mg) occurring Q2M thereafter. Participants continued to receive the treatment until the study intervention was locally approved and commercially available. Participants who received at least one dose of CAB LA and/or RPV LA and discontinued the CAB LA + RPV LA regimen for any reason entered a 52-week long-term follow-up (LTFU) Phase.

Drug: CAB LA; Drug: RPV LA

DTG + RPV

EXPERIMENTAL

Eligible participants from LAI116482 (NCT01641809 \[LATTE\]) study who were administered oral CAB 30 mg plus RPV 25 mg and who successfully completed Week 300 received their first dose of the Dolutegravir (DTG) 50 mg plus RPV 25 mg, once daily as oral regimen on Day 1 until Month 12 in the current study. These participants were not eligible for the LTFU phase.

Drug: RPV; Drug: DTG

LTFU: CAB LA+RPV LA Q2M Group

EXPERIMENTAL

This group included the participants who received at least one dose of CAB LA and/or RPV LA and discontinued the CAB LA + RPV LA regimen for any reason before end of Maintenance Period. The participants entered a 52-week LTFU period.

Drug: CAB LA; Drug: RPV LA

Interventions

CAB LA DRUG

Administered CAB LA (600 mg) Q2M, as intramuscular injection.

CAB LA + RPV LA Q2M; LTFU: CAB LA+RPV LA Q2M Group

RPV LA DRUG

Administered RPV LA (900 mg), Q2M, as intramuscular injection.

CAB LA + RPV LA Q2M; LTFU: CAB LA+RPV LA Q2M Group

RPV DRUG

Oral dose of RPV 25 mg, administered once daily from Day 1 up to Month 12

DTG + RPV

DTG DRUG

Oral dose of DTG 50 mg administered once daily from Day 1 up to Month 12.

DTG + RPV

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years or older (or \>=19 where required by local regulatory agencies), at the time of signing the informed consent.
• A female participant is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin \[hCG\] test at Day 1), not lactating, and at least with one of following conditions:
• (a) Non-reproductive potential defined as: (i) Pre-menopausal females with one of the conditions as documented tubal ligation; Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy.
• (ii) Postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels)\]. 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.
• (b) 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 the methods of contraception.
• Capable of giving signed informed consent.
• Must have been on oral CAB 30 mg plus RPV 25 mg regimen through at minimum Week 300 of the LATTE study as per LATTE protocol dosing requirements and until Day 1 of the POLAR study. Any disruptions in dosing during LATTE must be discussed with the Medical Monitor for a final determination of eligibility.
• Plasma HIV-1 RNA \<50 c/mL at Week 300. If participant has plasma HIV-1 RNA \>= 50 c/mL at Week 300 in LATTE, a single repeat to determine eligibility may be allowed ONLY after consultation with the medical monitor.

You may not qualify if:

• During the last 6 months of participation in LATTE, consecutive (2 or more sequential) plasma HIV-1 RNA measurements \>=50 c/mL.
• During the last 6 months of participation in LATTE, any HIV-1 RNA measurement \>=200 c/mL.
• Any evidence of a current Center for Disease Control and Prevention (CDC) Stage 3 disease \[CDC, 2014\], except cutaneous Kaposi's sarcoma not requiring systemic therapy.
• Participants with moderate to severe hepatic impairment determined by Child-Pugh classification.
• 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 enrolment if the Investigator believes the risk of seizure recurrence is low.
• 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.
• Participants 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 for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antibody (anti-HBs) and HBV 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.
• 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 within 12 months must be excluded. (HCV treatment on study may be permitted, following consultation with the medical monitor).
• Participants with HCV co-infection will be allowed entry into this study if: Liver enzymes meet entry criteria; HCV Disease has undergone appropriate work-up, and is not advanced.
• 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.
• 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.

Sponsors & Collaborators

• ViiV Healthcare: lead
• Janssen, LP: collaborator

Study Sites (30)

GSK Investigational Site

Phoenix, Arizona, 85015, United States

Location

GSK Investigational Site

Bakersfield, California, 93301, United States

Location

GSK Investigational Site

Beverly Hills, California, 90211, United States

Location

GSK Investigational Site

Long Beach, California, 90813, United States

Location

GSK Investigational Site

Los Angeles, California, 90069, United States

Location

GSK Investigational Site

Denver, Colorado, 80209, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20007, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20037, United States

Location

GSK Investigational Site

Fort Lauderdale, Florida, 33316, United States

Location

GSK Investigational Site

Ft. Pierce, Florida, 34982, United States

Location

GSK Investigational Site

Orlando, Florida, 32803, United States

Location

GSK Investigational Site

West Palm Beach, Florida, 33407, United States

Location

GSK Investigational Site

Augusta, Georgia, 30912-3130, United States

Location

GSK Investigational Site

Macon, Georgia, 31201, United States

Location

GSK Investigational Site

Savannah, Georgia, 31401, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46202, United States

Location

GSK Investigational Site

Omaha, Nebraska, 68198, United States

Location

GSK Investigational Site

Las Vegas, Nevada, 89106, United States

Location

GSK Investigational Site

Buffalo, New York, 14215, United States

Location

GSK Investigational Site

New York, New York, 10032, United States

Location

GSK Investigational Site

New York, New York, 10065, United States

Location

GSK Investigational Site

Charleston, South Carolina, 29425, United States

Location

GSK Investigational Site

Austin, Texas, 78705, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

Location

GSK Investigational Site

Annandale, Virginia, 22003, United States

Location

GSK Investigational Site

Vancouver, British Columbia, V6Z 2T1, Canada

Location

GSK Investigational Site

Toronto, Ontario, M4N 3M5, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 1K2, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2L 4E9, Canada

Location

GSK Investigational Site

Montreal, Quebec, H3A 1T1, Canada

Location

Related Publications (2)

• Okesanya OJ, Ayeni RA, Amadin P, Ngwoke I, Amisu BO, Ukoaka BM, Ahmed MM, Oso TA, Musa SS, Lucero-Prisno DE. Advances in HIV Treatment and Vaccine Development: Emerging Therapies and Breakthrough Strategies for Long-Term Control. AIDS Res Treat. 2025 Jul 4;2025:6829446. doi: 10.1155/arat/6829446. eCollection 2025.

  PMID: 40655875 DERIVED

• Mills A, Richmond GJ, Newman C, Osiyemi O, Cade J, Brinson C, De Vente J, Margolis DA, Sutton KC, Wilches V, Hatch S, Roberts J, McCoig C, Garris C, Vandermeulen K, Spreen WR. Long-acting cabotegravir and rilpivirine for HIV-1 suppression: switch to 2-monthly dosing after 5 years of daily oral therapy. AIDS. 2022 Feb 1;36(2):195-203. doi: 10.1097/QAD.0000000000003085.

  PMID: 34652287 DERIVED

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: ViiV Healthcare

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study, thus no masking.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an Intervention Model, with parallel assignment, where the primary purpose of the study is, treatment, with 2 arms and no masking.

Study Record Dates

• First Submitted: August 10, 2018
• First Posted: August 21, 2018
• Study Start: September 24, 2018
• Primary Completion: December 11, 2019
• Study Completion: January 30, 2023
• Last Updated: June 11, 2024
• Results First Posted: January 15, 2021

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available, within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided, after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided, for an initial period of 12 months but an extension can be granted, when justified for up to another 12 months.

Locations

CA (5); US (25)