A Phase 2b, Randomized, Active-Controlled, Double-Blind, Dose-Ranging Clinical Study to Evaluate a Switch to Islatravir (ISL) and MK-8507 Once-Weekly in Adults With HIV-1 Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) Once-Daily
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 161
- 试验地点
- 23
- 主要终点
- Percentage of Participants Who Experienced One or More Adverse Events (AEs) During the Double-Blind Treatment Period +42 Days Post-Blind
研究概览
简要总结
This is a randomized, controlled, double-blind, study to evaluate the safety and tolerability of islatravir (ISL) + ulonivirine based on review of the accumulated safety data, in adult participants with human immunodeficiency virus type 1 (HIV-1) who have been virologically suppressed for ≥6 months on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) once-daily.
详细描述
Based on laboratory findings of decreased lymphocyte and CD4+ T-cell counts across the islatravir program and as described in protocol amendment 2 (approved 01-Dec-2021), participants in study Part 1 (double-blind treatment period) were unblinded, discontinued all study interventions, and switched to standard of care non-study antiretroviral (ART) therapy. Participants who received ISL + ulonivirine (Groups 1 to 3) may have then entered into an unblinded safety monitoring period and were monitored for ≥6 months. As specified in protocol amendment 2, study Parts 2 and 3 were no longer planned or initiated for any participant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
In study Part 1 (double-blind treatment period), a double-blinding technique with in-house blinding is used. Ulonivirine, ISL, and BIC/FTC/TAF will be packaged identically relative to their matching placebos so that the blind is maintained. The participant, the investigator, and Sponsor personnel or delegate(s) who are involved in the study intervention administration or clinical evaluation of the participants are unaware of the intervention assignments.
In the unblinded safety monitoring period, participants, investigators, and Sponsor personnel are unblinded as to the participant's original randomized intervention group.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Is HIV-1 positive with plasma human immunodeficiency virus type 1 (HIV-1) RNA <50 copies/mL at screening
- •Has been virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) for ≥6 months
- •Has a screening CD4+ T-cell count >200 cells/mm^3 (completed by the central laboratory)
- •Is male or female, at least 18 years of age, at the time of signing the informed consent
- •Female participants are eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies:
- •Is not a woman of childbearing potential (WOCBP)
- •Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis)
排除标准
- •Has HIV-2 infection
- •Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
- •Has active hepatitis C virus (HCV) coinfection (defined as detectable HCV RNA) or hepatitis B virus (HBV) coinfection (defined as hepatitis B surface antigen [HBsAg]-positive or HBV deoxyribonucleic acid [DNA] positive)
- •Has a current (active) diagnosis of acute hepatitis due to any cause
- •Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or cutaneous Kaposi's sarcoma
- •Has a history or current evidence of any condition (including active tuberculosis infection), therapy, laboratory abnormality or other circumstance (including drug or alcohol use or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with the participant's participation for the full duration of the study
- •Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies
- •Is currently participating in or has participated in a clinical study with an investigational compound or device from 45 days prior to Day 1 through the study treatment period
- •Has a documented or known virological resistance to ulonivirine or nucleoside/nucleotide reverse transcriptase inhibitors (NNRTI)
- •Is female and expecting to conceive or donate eggs at any time during the study
研究组 & 干预措施
Group 1: ISL 20 mg + Ulonivirine 100 mg
Participants receive ISL 20 mg + ulonivirine 100 mg once weekly (QW) and placebo to BIC/FTC/TAF once daily (QD). Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART.
干预措施: Islatravir (Drug)
Group 1: ISL 20 mg + Ulonivirine 100 mg
Participants receive ISL 20 mg + ulonivirine 100 mg once weekly (QW) and placebo to BIC/FTC/TAF once daily (QD). Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART.
干预措施: Ulonivirine (Drug)
Group 1: ISL 20 mg + Ulonivirine 100 mg
Participants receive ISL 20 mg + ulonivirine 100 mg once weekly (QW) and placebo to BIC/FTC/TAF once daily (QD). Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART.
干预措施: Placebo to Ulonivirine (Drug)
Group 1: ISL 20 mg + Ulonivirine 100 mg
Participants receive ISL 20 mg + ulonivirine 100 mg once weekly (QW) and placebo to BIC/FTC/TAF once daily (QD). Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART.
干预措施: Placebo to BIC/FTC/TAF (Drug)
Group 2: ISL 20 mg + Ulonivirine 200 mg
Participants receive ISL 20 mg + ulonivirine 200 mg QW and placebo to BIC/FTC/TAF QD. Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART.
干预措施: Islatravir (Drug)
Group 2: ISL 20 mg + Ulonivirine 200 mg
Participants receive ISL 20 mg + ulonivirine 200 mg QW and placebo to BIC/FTC/TAF QD. Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART.
干预措施: Ulonivirine (Drug)
Group 2: ISL 20 mg + Ulonivirine 200 mg
Participants receive ISL 20 mg + ulonivirine 200 mg QW and placebo to BIC/FTC/TAF QD. Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART.
干预措施: Placebo to Ulonivirine (Drug)
Group 2: ISL 20 mg + Ulonivirine 200 mg
Participants receive ISL 20 mg + ulonivirine 200 mg QW and placebo to BIC/FTC/TAF QD. Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART.
干预措施: Placebo to BIC/FTC/TAF (Drug)
Group 3: ISL 20 mg + Ulonivirine 400 mg
Participants receive ISL 20 mg + ulonivirine 400 mg QW and placebo to BIC/FTC/TAF QD. Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART.
干预措施: Islatravir (Drug)
Group 3: ISL 20 mg + Ulonivirine 400 mg
Participants receive ISL 20 mg + ulonivirine 400 mg QW and placebo to BIC/FTC/TAF QD. Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART.
干预措施: Ulonivirine (Drug)
Group 3: ISL 20 mg + Ulonivirine 400 mg
Participants receive ISL 20 mg + ulonivirine 400 mg QW and placebo to BIC/FTC/TAF QD. Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART.
干预措施: Placebo to BIC/FTC/TAF (Drug)
Group 4: BIC/FTC/TAF
Participants receive placebo to ISL + placebo to ulonivirine QW and BIC/FTC/TAF 50 mg/200 mg/25 mg QD.
干预措施: BIC/FTC/TAF (Drug)
Group 4: BIC/FTC/TAF
Participants receive placebo to ISL + placebo to ulonivirine QW and BIC/FTC/TAF 50 mg/200 mg/25 mg QD.
干预措施: Placebo to ISL (Drug)
Group 4: BIC/FTC/TAF
Participants receive placebo to ISL + placebo to ulonivirine QW and BIC/FTC/TAF 50 mg/200 mg/25 mg QD.
干预措施: Placebo to Ulonivirine (Drug)
结局指标
主要结局
Percentage of Participants Who Experienced One or More Adverse Events (AEs) During the Double-Blind Treatment Period +42 Days Post-Blind
时间窗: Up to approximately 9 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. As pre-specified in the protocol and supplemental statistical analysis plan (sSAP), presented here is the percentage of participants who experienced one or more AEs during the Double-blind Treatment Period and includes the 42 days following the final dose of double-blind study intervention.
Percentage of Participants Who Discontinued Study Intervention Due to an AE During the Double-Blind Treatment Period
时间窗: Up to approximately 8 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. As pre-specified in the protocol and sSAP, presented here is the percentage of participants who discontinued double-blind study intervention due to an AE during the Double-Blind Treatment Period.
Percentage of Participants Who Experienced One or More AEs During the Unblinded Safety Monitoring Period
时间窗: Up to approximately 37 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. As pre-specified in the protocol and sSAP, presented here is the percentage of participants who experienced one or more AEs during the Unblinded Safety Monitoring Period, beginning 42 days following the final dose of double-blind study intervention.
次要结局
未报告次要终点