HIV Preexposure Prophylaxis
Conditions
Keywords
Preexposure prophylaxis (PrEP), Prevention
Brief summary
The main purpose of the study is to evaluate the safety and tolerability of oral Islatravir (ISL) once monthly (QM) as Preexposure Prophylaxis (PrEP) in cisgender men who have sex with men (MSM) and transgender women (TGW) who have sex with men and who are at high risk of HIV-1 infection with 48 or 96 weeks of treatment and a minimum follow-up of 42 days.
Detailed description
Based on laboratory findings of decreased lymphocyte and CD4+ T-cell counts across the islatravir program, dosing of blinded study intervention was halted on 13-Dec-2021. Blinded assessments conducted prior to then are designated as Study Part 1. During Study Part 2, participants from Part 1 were switched to PrEP therapy with emtricitabine/tenofovir disoproxil (FTC/TDF) or emtricitabine/tenofovir alafenamide (FTC/TAF) while continuing in the study, but participants, investigators, and Sponsor personnel remained blinded to the Part 1 treatment. In Part 3, participants, investigators, and all Sponsor personnel are unblinded to participant's original randomized intervention group, and participants may continue to receive unblinded FTC/TDF or FTC/TAF.
Interventions
DRUGISL
ISL 60 mg tablet, QM, orally for up to 24 months
DRUGFTC/TDF
Participants receive 200/245 mg of FTC/TDF combination tablet, QD, orally for up to 24 months
DRUGFTC/TAF
Participants receive 200/25 mg of FTC/TAF combination tablet, QD, orally for up to 24 months
DRUGPlacebo to ISL
Placebo ISL 0 mg tablets QM, orally for up to 24 months.
Placebo FTC/TDF 0 mg tablets QD, orally for up to 24 months
DRUGPlacebo to FTC/TAF
Placebo FTC/TAF 0 mg tablets QD, orally for up to 24 months
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Masking description
In Study Part 1, double-blind with in-house blinding is used. In Study Part 2, sponsor personnel not directly involved with blinded safety monitoring will be unblinded to participants' randomized study intervention in Part 1 (personnel involved with Part 2 will remain blinded). In Study Part 3, al participants, investigators, and Sponsor personnel are unblinded as to the participant's original randomized intervention group.
Eligibility
Sex/Gender
MALE
Age
16 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Has confirmed Human Immunodeficiency Virus (HIV) uninfected based on negative HIV-1/HIV-2 test result before randomization * Is sexually active with male or transgender women (TGW) partners defined as having anal sexual intercourse with a man or TGW at least once in the past month * Is at high risk for sexually acquiring HIV-1 infection based on self-report of at least 1 of the following: a) Condomless receptive anal intercourse in the 6 months prior to screening occurring outside a mutually monogamous HIV seronegative concordant relationship b) More than 5 partners (anal intercourse) in the 6 months prior to screening c) Any unprescribed stimulant drug use in the 6 months prior to screening d) Rectal or urethral gonorrhea or chlamydia or incident syphilis in the 6 months prior to screening * Participants 16 or 17 years of age must weigh ≥35 kg. Enrollment for 16- to 17-year-old participants will begin only after completion of the Sentinel Cohort IA and review of IA results by the external data monitoring committee (eDMC) * Has no plans to relocate or travel away from the site for ≥4 consecutive weeks during study participation
Exclusion criteria
* Has hypersensitivity or other contraindication to any component of the study interventions as determined by the investigator * Has chronic HBV infection or past HBV infection which could indicate risk for Hepatitis B reactivation * Has known current or chronic history of liver disease or known hepatic or biliary abnormalities, unless the participant has stable liver function tests and no evidence of hepatic synthetic dysfunction * Has a history of malignancy within 5 years of screening except for adequately treated basal cell or squamous cell skin cancer or in situ anal cancers * Has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance 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, such that it is not in the best interest of the participant to enroll * Has taken cabotegravir, lenacapavir, or any other long-acting HIV prevention product at any time * Is currently receiving or is anticipated to require any prohibited therapies outlined in the study from 30 days prior to Day 1 through the duration of the study * Is currently participating in or has participated in an interventional or prevention clinical study with an investigational compound or device, within 30 days prior to Day 1 through the duration of the study * Has exclusionary laboratory values within 45 days prior to Day 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event (AE) During Blinded Treatment | Up to approximately 10.5 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. The number of participants who experienced an AE will be reported for each treatment arm. |
| Number of Participants Who Discontinued From Blinded Study Treatment Due to an AE | 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. The number of participants who experienced an AE will be reported for each treatment arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Confirmed HIV-1 Infection | Up to approximately 10.5 months | The number of participants with confirmed HIV-1 infections during the blinded treatment period is presented. |
Countries
Brazil, France, Japan, Peru, South Africa, Thailand, United States
Participant flow
Pre-assignment details
Participants were randomized at 23 study sites in France, Japan, Peru, South Africa, and the United States.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: ISL & Parts 2 & 3: FTC/TDF or FTC/TAF Participants received 60 mg tablet of ISL QM plus placebo to FTC/TDF tablet QD or placebo to FTC/TAF tablet QD in Part 1. Participants then received open-label FTC/TDF or FTC/TAF in Parts 2 and 3. | 328 |
| Parts 1 to 3: FTC/TDF or FTC/TAF Participants received 200/245 mg or 200/300 mg of FTC/TDF combination tablet QD or 200/25 mg of FTC/TAF combination tablet QD at investigator's discretion plus placebo to ISL tablet QM in Part 1. Participants continued to receive open-label FTC/TDF or FTC/TAF in Parts 2 and 3. | 166 |
| Total | 494 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part 1: Blinded Study Medication | Adverse Event | 1 | 0 |
| Part 1: Blinded Study Medication | Lost to Follow-up | 7 | 2 |
| Part 1: Blinded Study Medication | Multiple reasons (primarily discontinuation of blinded treatment) | 308 | 160 |
| Part 1: Blinded Study Medication | Withdrawal by Subject | 12 | 4 |
| Parts 2 and 3: Open-Label FTC TDF or TAF | Lost to Follow-up | 34 | 9 |
| Parts 2 and 3: Open-Label FTC TDF or TAF | Not reported | 6 | 1 |
| Parts 2 and 3: Open-Label FTC TDF or TAF | Physician Decision | 0 | 2 |
| Parts 2 and 3: Open-Label FTC TDF or TAF | Study terminated by Sponsor | 227 | 119 |
| Parts 2 and 3: Open-Label FTC TDF or TAF | Withdrawal by Subject | 39 | 23 |
Baseline characteristics
| Characteristic | Parts 1 to 3: FTC/TDF or FTC/TAF | Total | Part 1: ISL & Parts 2 & 3: FTC/TDF or FTC/TAF |
|---|---|---|---|
| Age, Continuous | 29.5 years STANDARD_DEVIATION 9.2 | 29.6 years STANDARD_DEVIATION 9.5 | 29.6 years STANDARD_DEVIATION 9.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 51 Participants | 162 Participants | 111 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 111 Participants | 325 Participants | 214 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 7 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 31 Participants | 101 Participants | 70 Participants |
| Race (NIH/OMB) Black or African American | 41 Participants | 124 Participants | 83 Participants |
| Race (NIH/OMB) More than one race | 20 Participants | 55 Participants | 35 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) White | 71 Participants | 206 Participants | 135 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 166 Participants | 494 Participants | 328 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 328 | 0 / 306 | 0 / 166 | 0 / 154 |
| other Total, other adverse events | 120 / 328 | 230 / 306 | 88 / 166 | 104 / 154 |
| serious Total, serious adverse events | 6 / 328 | 18 / 306 | 1 / 166 | 5 / 154 |
Outcome results
Primary
Number of Participants Who Discontinued From Blinded Study Treatment Due to an AE
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. The number of participants who experienced an AE will be reported for each treatment arm.
Time frame: Up to approximately 9 months
Population: All treated participants are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: ISL & Parts 2 & 3: FTC/TDF or FTC/TAF | Number of Participants Who Discontinued From Blinded Study Treatment Due to an AE | 1 Participants |
| Parts 1 to 3: FTC/TDF or FTC/TAF | Number of Participants Who Discontinued From Blinded Study Treatment Due to an AE | 0 Participants |
Primary
Number of Participants Who Experienced an Adverse Event (AE) During Blinded Treatment
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. The number of participants who experienced an AE will be reported for each treatment arm.
Time frame: Up to approximately 10.5 months
Population: All treated participants are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: ISL & Parts 2 & 3: FTC/TDF or FTC/TAF | Number of Participants Who Experienced an Adverse Event (AE) During Blinded Treatment | 211 Participants |
| Parts 1 to 3: FTC/TDF or FTC/TAF | Number of Participants Who Experienced an Adverse Event (AE) During Blinded Treatment | 128 Participants |
Secondary
Number of Participants With Confirmed HIV-1 Infection
The number of participants with confirmed HIV-1 infections during the blinded treatment period is presented.
Time frame: Up to approximately 10.5 months
Population: All participants who were randomized and received ≥1 dose of study intervention are included (participants with confirmed HIV infections prior to or at randomization are excluded).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: ISL & Parts 2 & 3: FTC/TDF or FTC/TAF | Number of Participants With Confirmed HIV-1 Infection | 0 Participants |
| Parts 1 to 3: FTC/TDF or FTC/TAF | Number of Participants With Confirmed HIV-1 Infection | 0 Participants |