Human Immunodeficiency Virus type 1 (HIV-1) MedDRA version: 19.0 Level: LLT Classification code 10003582 Term: Asymptomatic human immunodeficiency virus type I infection System Organ Class: 100000004862
Conditions
Sponsors
ViiV Healthcare, S.L.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 including the use and benefit/ri
Exclusion criteria
Exclusion criteria: Exclusionary Criteria prior to Screening or Day 1 1. Within 6 months prior to Screening and after confirmed suppression to or=50 c/mL 2. Within the 6 to 12 month window prior to Screening and after confirmed suppression to 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 require HCV treatment withi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the non-inferior antiviral activity of switching to intramuscular CAB LA + RPV LA every 4 weeks (monthly) compared to continuation of current first line antiretroviral regimen over 48 weeks in HIV-1 infected antiretroviral therapy (ART)- experienced participants;Secondary Objective: Refer to protocol (section 3) for complete list of Secondary Endpoints -To demonstrate the antiviral and immunologic activity of switching to intramuscular CAB LA + RPV LA every 4 weeks (monthly) compared to continuation of current ART -To evaluate the safety and tolerability of switching to CAB LA + RPV LA every 4 weeks (monthly) compared to continuation of current ART -To assess viral resistance in participants experiencing protocol-defined virologic failure -To assess the impact of Baseline third agent treatment class (INI, NNRTI, or PI) on efficacy, safety, tolerability, and viral resistance of CAB LA + RPV LA compared to continuation of current ART -To characterize CAB and RPV concentrations and population pharmacokinetics and identify important determinants of variability. -To evaluate the antiviral and immunologic effects, safety, tolerability, and viral resistance of CAB LA + RPV LA for participants during the Extension Phase;Primary end point(s): Proportion of participants with a ‘virologic failure’ endpoint as per Food and Drug Administration (FDA) Snapshot algorithm at Week 48 (Intent-to-Treat Exposed [ITT-E] population).;Timepoint(s) of evaluation of this end point: 48 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Proportion of participants with Plasma HIV-1 RNA or= 200 c/mL after prior suppression to <200 c/mL) at Weeks 48, and 96. •Absolute values and change from Baseline in plasma HIV-1 RNA (log10 c/mL) at Weeks 48, and 96. •Absolute values and change from Baseline in CD4+ lymphocyte count at Weeks 48, and 96. •Incidence and severity of adverse events (AEs) and laboratory abnormalities over time including Weeks 48 and 96. •Absolute values and changes in laboratory parameters over time including Weeks 48 and 96 •Proportion of participants who discontinue treatment due to AEs over time including Weeks 48 and 96 •Incidence of disease progression (HIV-associated conditions, acquired immunodeficiency syndrome [AIDS] and death over 48 Weeks •Plasma PK parameters for CAB LA and RPV LA (when evaluable, Ctrough, concentrations post dose [~Cmax], and area under the curve [AUC]) •Proportion of participants who discontinue treatment due to AEs over time including Week 96 •Incidence of treatment emergent genotypic and phenotypic resistance to CAB, RPV, and other on study ART at Week 96 •Dimension scores (“Bother of ISRs”, “Leg movement”, “Sleep”, and “Acceptance)_ and individual item scores assessing pain during injection, anxiety before and after injection, willingness to be injected in the future and overall satisfaction with mode of administration over time using the Perception of iNjection questionnaire (PIN) •Proportion of participants considering pain and local reactions following injection to be extremely or very acceptable based on the acceptability score over time using the Perception of iNjection questionnaire (PIN) •Summary statistics and between and within treatment group comparisons of change in HRQoL from Baseline and Weeks 24, 48, 96 (or Withdrawal). •Summary statistics and between and within treatment group comparisons of change in health status using the 12-item Short Form Health Survey (SF-12) from Baseline and Weeks 24, 48, 96 (or Withdrawa | — |
Countries
Argentina, Australia, Canada, France, Germany, Italy, Korea, Democratic People's Republic of, Mexico, Russian Federation, South Africa, Spain, Sweden, United States
Contacts
Public ContactCentro de Información
GlaxoSmithKline
Outcome results
None listed