HIV-1 Infection
Conditions
Brief summary
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.
Detailed description
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.
Interventions
Placebo tablet matched to BIC/FTC/TAF taken by mouth.
DRUGIslatravir
ISL capsule taken by mouth.
DRUGUlonivirine
Ulonivirine tablet taken by mouth.
DRUGBIC/FTC/TAF
BIC/FTC/TAF tablet taken by mouth.
DRUGPlacebo to ISL
Placebo capsule matched to ISL taken by mouth.
DRUGPlacebo to Ulonivirine
Placebo tablet matched to ulonivirine taken by mouth.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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)
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced One or More Adverse Events (AEs) During the Double-Blind Treatment Period +42 Days Post-Blind | 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 | 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 | 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. |
Countries
France, Switzerland, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Pre-assignment details
As pre-specified in protocol amendment 2, participants in the Double-blind Treatment Period discontinued all study interventions (islatravir \[ISL\], ulonivirine, or bictegravir/emtricitabine/tenofovir alafenamide \[BIC/FTC/TAF\]). Participants who received ISL + ulonivirine may have then entered the Unblinded Safety Monitoring Period and received standard of care non-study antiretroviral therapy (ART), provided by the investigator, until study completion or discontinuation.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 45.4 Years STANDARD_DEVIATION 11.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 104 Participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 41 | 0 / 40 | 0 / 40 | 0 / 37 | 0 / 39 | 0 / 37 |
| other Total, other adverse events | 18 / 40 | 15 / 41 | 25 / 40 | 14 / 40 | 8 / 37 | 16 / 39 | 16 / 37 |
| serious Total, serious adverse events | 2 / 40 | 3 / 41 | 1 / 40 | 0 / 40 | 0 / 37 | 0 / 39 | 1 / 37 |
Outcome results
None listed