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
Interventions
Product Name: Cabotegravir (CAB)
Product Code: GSK1265744
Pharmaceutical Form: Tablet
INN or Proposed INN: Cabotegravir Sodium
CAS Number: 1051375-13-3
Current Sponsor code: GSK1265744
Other descripti
Sponsors
ViiV Healthcare, S.L.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants eligible for enrollment in the study must meet all of the following criteria: AGE 1. HIV-1 infected, ART-naive 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. HIV-1 infection as documented by Screening plasma HIV-1 RNA =1000 c/mL; 3. Antiretroviral-naïve (=10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection). Any previous exposure to an HIV integrase inhibitor or non-nucleoside reverse transcriptase inhibitor will be exclusionary. SEX 4. Female Participants: A female participant is eligible to participate if she is not pregnant at Screening and first day of Induction Phase (as confirmed by a negative serum human chorionic gonadotrophin [hCG] test), 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 Appendix 7.) 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. ALL participants in the study should be counseled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g., male condom) and on the risk of HIV transmission to an uninfected partner. INFORMED CONSENT Capable of giving signed informed consent as described in Section 6.2 which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. OTHER French participants: In France, a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 590 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: A participant will not be eligible for inclusion in this study if any of the following criteria apply: Exclusionary Medical Conditions 1. Women who are pregnant, breastfeeding, or plan to become pregnant or breastfeed during the study. 2. Any evidence at Screening of an active Centers for Disease and Prevention Control (CDC) Stage 3 disease [CDC, 2014], except cutaneous Kaposi’s sarcoma not requiring systemic therapy or historic or current CD4+ cell count 3.25 is exclusionary Fib-4 scores 1.45 – 3.25 requires Medical Monitor consultation. Fibrosis 4 Score Formula: (Age x AST) / (Platelets x (
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 compared to continuation of ABC/DTG/3TC over 48 weeks in HIV-1 antiretroviral naïve participants.;Secondary Objective: -To demonstrate the antiviral and immunologic activity of switching to intramuscular CAB LA + RPV LA every 4 weeks compared to continuation of ABC/DTG/3TC. -To evaluate the safety and tolerability of switching to CAB LA + RPV LA every 4 weeks compared to continuation of ABC/DTG/3TC over time. -To evaluate the effects of CAB LA + RPV LA every 4 weeks on fasting lipids over time compared to continuation of ABC/DTG/3TC over time. -To assess the development of viral resistance in participants experiencing protocol-defined virologic failure.- -To characterize CAB and RPV concentrations and population pharmacokinetics and identify important determinants of variability. -To assess the acceptance of pain and injection site reactions following injections. -To assess degree of health-related quality of life (HR QoL) using the HIV/AIDS-targeted quality of life (HAT-QoL) questionnaire short form. Please refer to the protocol P30 for further details;Primary end point(s): Proportion of participants with a ‘virologic failure’ endpoint as per FDA Snapshot algorithm at Week 48 (Missing, Switch or Discontinuation = Failure, Intent-to-Treat Exposed [ITT-E] population).;Timepoint(s) of evaluation of this end point: Week 48 of Maintenance Phase | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Proportion of participants with Plasma HIV-1 RNA <50 c/mL at Week 48 using the FDA Snapshot algorithm (ITT-E population). • Proportion of participants with plasma HIV-1 RNA <200 c/mL at Week 48 using the FDA Snapshot algorithm (ITT-E population). • Proportion of participants with plasma HIV-1 RNA <200 c/mL and HIV-1 RNA <50 c/mL at Week 96 using the FDA Snapshot algorithm (ITT-E population). • Proportion of participants with a ‘virologic failure’ endpoint as per FDA Snapshot algorithm at Week 96. • Proportion of participants with confirmed virologic failure at Week 48 and Week 96. • Absolute values and change from Baseline in plasma HIV-1 RNA at Week 48 and Week 96. • Absolute values and changes from Baseline in CD4+ cell counts over time including Week 48 and Week 96. • Incidence of disease progression (HIV-associated conditions, acquired immunodeficiency syndrome [AIDS] and death). • Incidence and severity of AEs and laboratory abnormalities over time including Week 48 and Week 96. • Proportion of participants who discontinue treatment due to AEs over time including Week 48 and Week 96. • Absolute values and changes in laboratory parameters over time including Week 48 and Week 96. • Change from Baseline in fasting lipids over time including Week 48 and Week 96. • Incidence of treatment emergent genotypic and phenotypic resistance to CAB, RPV, and other on-study ART at Week 48 and Week 96. • Plasma PK parameters for CAB LA and RPV LA (when evaluable, Ctrough. concentrations post dose [~Cmax], and area under the curve [AUC]). • Demographic parameters including, but not limited to age, sex, race, body weight, body mass index, and relevant laboratory parameters will be evaluated as potential predictors of inter- and intra-participant variability for pharmacokinetic parameters. • Dimension scores (e.g., “Bother of ISRs”, “Leg movement”, “Sleep”, and “Acceptance) and individual item scores assessing pain during injection, anxiety before and | — |
Countries
Canada, France, Germany, Italy, Japan, Netherlands, Russian Federation, South Africa, Spain, United Kingdom, United States
Contacts
Public ContactCentro de Información
GlaxoSmithKline
Outcome results
None listed