Long-term Follow-up of Long-acting Cabotegravir (CAB LA) for PrEP (Pre-exposure Prophylaxis) in Participants at Risk of Acquiring HIV (Human Immunodeficiency Virus)

HIV Infections Clinical Trial

— PALISADE  

Official title:

A Phase IIIB, Long-Term Follow-Up of CAB LA for Participants in HPTN 083 and HPTN 084 CAB PrEP Studies at Risk of HIV Acquisition

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06134362
• Other study ID #: 221163
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: April 1, 2024
• Est. completion date: June 24, 2027

Study information

• Verified date: January 2024
• Source: ViiV Healthcare
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is long-term evaluation of long-acting injectable cabotegravir (CAB LA) for HIV pre-exposure prophylaxis (PrEP) in eligible participants who have completed DAIDS (Division of AIDS) sponsored studies HPTN 083 and HPTN 084 and associated sub-studies. Participants will continue receiving CAB LA and be followed for new HIV diagnosis, SAEs (serious adverse events), Grade 3 and Grade 4 ISRs (injection site reactions), and AEs (adverse events) leading to withdrawal.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 3500
• Est. completion date: June 24, 2027
• Est. primary completion date: June 24, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

1. Participants must be currently enrolled and ongoing in one of the following studies:

• HPTN 083
• HPTN 084
• HPTN 083 and HPTN 084 adolescent and pregnancy sub-studies Participants who have permanently withdrawn from prior CAB PrEP studies cannot enroll into this study.

2. Evidence of continued benefit (HIV negative and at risk) from CAB LA during participation in the parent study/sub-study.

3. Participants must have a nonreactive HIV test at Screening (rapid test, antigen/antibody test and HIV-1 RNA from the parent study/sub-study) and Day 1 (a rapid test and HIV Immunoassay [Antigen/Antibody test]).

4. Males and Females:

All participants who are engaging in sexual activity should be counselled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g., male condom) and on the risk of acquiring HIV and other STIs. Females: Cisgender female participants who are of childbearing potential and who are engaging in sexual activity that could lead to pregnancy, must talk to the investigator about recommended contraception options. Contraception will be optional in this study. Condoms are recommended in addition, because their appropriate use is the only contraception method effective for preventing HIV-1 transmission. Pregnant participants from the HPTN 084 study are eligible to enroll into this study if they meet all eligibility criteria. Exclusion Criteria:

Concurrent conditions/medical history (includes liver function):

1. Participants who are currently enrolled in the eligible studies on the TDF/FTC arm are not eligible to enroll into this study. Participants receiving short-term oral TDF/FTC bridging may be enrolled following consultation with the Medical Monitor.

2. Previous permanent discontinuation from IP in the parent study/sub-study.

3. Known ALT >5 x ULN or ALT>3 x ULN and bilirubin >1.5 x ULN (with >35% direct bilirubin).

4. Participants with known hepatitis B infection at any time prior to entry (as evidence by a positive Hepatitis B virus surface antigen positive and/or quantifiable Hepatitis B DNA PCR).

5. 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 hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator).

6. Known history of cirrhosis with or without viral hepatitis co-infection.

7. Participant is currently participating in or has participated in a study (other than the studies listed in Inclusion Criteria 1) with a compound or device that is not commercially available within 30 days of signing informed consent, unless permission from the Medical Monitor is granted.

8. Presence of any history of allergy/sensitivity to any of the study drug.

9. Inflammatory skin conditions that compromise the safety of IM injections, per the discretion of the investigator. Mild skin conditions may not be exclusionary at the discretion of the investigator or designee.

10. Participant has a gluteal implant, tattoo or other dermatological condition overlying the buttock region which in the opinion of the investigator or designee may interfere with the injection or interpretation of ISRs.

11. Coagulopathy (primary or iatrogenic) which would contraindicate IM injection.

Concomitant medications:

12. Use of any disallowed medications at time of screening.

13. Anticipated need for HCV therapy with interferon or any drugs that have potential for adverse drug: drug interactions with study treatment throughout the entire study period.

Relevant habits:

14. Participant is unlikely to adhere to the study procedures, keep appointments, or is planning to relocate during the study.

15. Any condition (including but not limited to alcohol and drug use) that would, in the opinion of the site investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• CAB LA
Participants will receive CAB LA 600 mg via gluteal IM injection, once every 8 weeks (Q8W).

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Almagro	Ciudad Autónoma De BuenosAires
Argentina	GSK Investigational Site	Buenos Aires
Botswana	GSK Investigational Site	Francistown	North-East
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Rio de Janeiro
Brazil	GSK Investigational Site	Sao Paulo	São Paulo
Brazil	GSK Investigational Site	São Paulo
Kenya	GSK Investigational Site	Kisumu	Nyanza
Malawi	GSK Investigational Site	Blantyre
Malawi	GSK Investigational Site	Lilongwe
Peru	GSK Investigational Site	Barranco	Lima
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Piura
South Africa	GSK Investigational Site	Cape Town	Western Cape
South Africa	GSK Investigational Site	Cape Town	Western Cape
South Africa	GSK Investigational Site	City Of Cape Town	Western Cape
South Africa	GSK Investigational Site	City Of Johannesburg	Gauteng
South Africa	GSK Investigational Site	Ethekwini	Kwazulu - Natal
South Africa	GSK Investigational Site	Ethekwini	Kwazulu - Natal
South Africa	GSK Investigational Site	Eveni
South Africa	GSK Investigational Site	Isipingo	KwaZulu - Natal
South Africa	GSK Investigational Site	Sol Plaatjie	Northern Cape
Thailand	GSK Investigational Site	Muang Chiang Mai
Thailand	GSK Investigational Site	Pathum Wan	Krung Thep Maha Nakhon-Bangkok
Uganda	GSK Investigational Site	Enteebe
Uganda	GSK Investigational Site	Kampala
Uganda	GSK Investigational Site	Kampala
Vietnam	GSK Investigational Site	Huyen Tu Liem	Ha Noi, Thu Do
Zimbabwe	GSK Investigational Site	Chitungqiza
Zimbabwe	GSK Investigational Site	Chitungwiza	Harare
Zimbabwe	GSK Investigational Site	Chitungwiza	Harare
Zimbabwe	GSK Investigational Site	Harare
Zimbabwe	GSK Investigational Site	Harare

Sponsors (3)

Lead Sponsor	Collaborator
ViiV Healthcare	GlaxoSmithKline, PPD

Countries where clinical trial is conducted

Argentina,  Botswana,  Brazil,  Kenya,  Malawi,  Peru,  South Africa,  Thailand,  Uganda,  Vietnam,  Zimbabwe, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with new HIV infection		From Day 1 up to end of study (up to approximately [approx.] 3 years)
Primary	Number of participants with new HIV infection by characteristic	Relevant characteristics of new HIV infections will be assessed, including presence of viral resistance to CAB.	From Day 1 up to end of study (up to approx. 3 years)
Secondary	Number of participants with serious adverse events (SAE) by severity	The severity scale is assessed as following: Grade 1 = mild symptoms causing no or minimal interference with usual social and functional activities with intervention not indicated. Grade 2 = moderate symptoms causing greater than minimal interference with usual social and functional activities with intervention indicated. Grade 3 = severe symptoms causing inability to perform usual social and functional activities with intervention or hospitalization indicated. Grade 4 = potentially life-threatening symptoms causing inability to perform self-care functions with intervention indicated to prevent permanent impairment, persistent disability, or death.	From Day 1 up to end of study (up to approx. 3 years)
Secondary	Number of participants with Grade 3 and Grade 4 injection site reactions (ISRs)	ISRs may occur following intramuscular administration of CAB LA. Grade 3 refers to severe symptoms causing inability to perform usual social & functional activities with intervention or hospitalization indicated. Grade 4 refers to potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability or death.	From Day 1 up to end of study (up to approx. 3 years)
Secondary	Number of participants with any clinical or laboratory AE leading to discontinuation of CAB LA, by severity	Any clinical or laboratory AE that leads the participant to permanently discontinue CAB LA will be assessed. The severity scale is assessed as following: Grade 1 = mild symptoms causing no or minimal interference with usual social and functional activities with intervention not indicated. Grade 2 = moderate symptoms causing greater than minimal interference with usual social and functional activities with intervention indicated. Grade 3 = severe symptoms causing inability to perform usual social and functional activities with intervention or hospitalization indicated. Grade 4 = potentially life-threatening symptoms causing inability to perform self-care functions with intervention indicated to prevent permanent impairment, persistent disability, or death.	From Day 1 up to end of study (up to approx. 3 years)