A Phase III study to compare two drugs (called Cabotegravir and Rilpivirine, as oral tablets followed by long-acting injections) to current HIV regimens containing three drugs
- Conditions
- Human Immunodeficiency Virus type 1 (HIV-1)MedDRA version: 20.1Level: LLTClassification code 10003582Term: Asymptomatic human immunodeficiency virus type I infectionSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2016-001647-39-SE
- Lead Sponsor
- ViiV Healthcare UK Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 616
AGE
1. HIV-1 infected men or women aged 18 years or greater at the time of signing the informed consent
TYPE OF PARTICIPANT AND DIAGNOSIS INCLUDING DISEASE SEVERITY
2. Must be on uninterrupted current regimen (either the initial or second ARV regimen) for at least 6 months prior to Screening. Any prior switch, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability/safety, access to medications, or convenience/simplification, and must NOT have been done for treatment failure (HIV-1 RNA =400 c/mL).
Acceptable stable (initial or second) ARV regimens prior to Screening include 2 NRTIs plus:
-INI with the exception of ABC/DTG/3TC (either the initial or second cART regimen)
-NNRTI (either the initial or second cART regimen)
-Boosted PI (or atazanavir [ATV] unboosted) (either the initial or second PI-based cART regimen)
3. Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12 months prior to Screening: one within the 6 to 12 month window, and one within 6 months prior to Screening;
4. Plasma HIV-1 RNA <50 c/mL at Screening;
SEX
5. A female participant is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test at screen and a negative urine hCG test at Randomization), not lactating, and at least one of the following conditions applies:
a. Non-reproductive potential defined as:
-Pre-menopausal females with one of the following:
-Documented tubal ligation
-Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion
-Hysterectomy
-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 (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) (see Section 12.7.1, Appendix 7) from 30 days prior to the first dose of study medication and until from 30 days prior to the first dose of study medication throughout the study, and 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.
INFORMED CONSENT
Capable of giving signed informed consent as described in Section 10.2, which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. Eligible participants or their legal guardians must sign a written Informed
Consent Form before any protocol-specified assessments are conducted.
OTHER
Participants enrolled in France must be affiliated to, or a beneficiary of, a social security category.
All participants participating in the study should be counselled on safer sexual practices i
Exclusionary Criteria prior to Screening or Day 1
1. Within 6 months prior to Screening and after confirmed suppression to <50 c/mL on current ART regimen, any plasma HIV-1 RNA measurement >or=50 c/mL
2. Within the 6 to 12 month window prior to Screening and after confirmed suppression to <50 c/mL, any plasma HIV-1 RNA measurement >200 c/mL, or 2 or more plasma HIV-1 RNA measurements >or=50 c/mL
3. Any drug holiday during the window between initiating first HIV ART and 6 months prior to Screening, except for brief periods where all ART was stopped due to tolerability and/or safety concerns
4. Any switch to a second line regimen, defined as change of a single drug or multiple drugs simultaneously, due to virologic failure to therapy
5. Abacavir/dolutegravir/lamivudine, (ABC/DTG/3TC) as current ART regimen
6. A history of use of any regimen consisting of only single NNRTI therapy, or only single or dual NRTI therapy prior to starting cART
7. Participants who are currently participating in or anticipate to be selected for any other interventional study
Exclusionary medical conditions
8. Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the study
9. Any evidence of an active Center for Disease Control and Prevention (CDC) Stage 3 disease, except cutaneous Kaposi’s sarcoma not requiring systemic therapy and historical or current CD4 cell counts less than 200 cells/mm3
10. Participants with moderate to severe hepatic impairment
11. Any pre-existing physical or mental condition 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
12. 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. All cases of prior seizure history should be discussed with the Medical Monitor prior to enrolment
13. All participants will be screened for syphilis. 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
14. 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
15. The participant has a tattoo or other dermatological condition overlying the gluteus region which may interfere with interpretation of injection site reactions
16. Evidence of Hepatitis B virus (HBV) infection based on the results of testing at
Screening 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 and positive for HBV DNA are excluded
17. 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 requ
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method