A clinical study of people with HIV‐1 who switch their treatment to a combination of doravirine and islatravir​​

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Decision date (initial)

2023-04-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-502079-49-00

WHO UTN

U1111-1283-0949

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacoeconomic, Efficacy, Pharmacokinetic, Pharmacogenomic, Therapy, Pharmacogenetic, Safety

1. To evaluate the antiretroviral activity of a switch to DOR/ISL compared with continued BIC/FTC/TAF, as assessed by the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48
2. To evaluate the safety and tolerability of a switch from BIC/FTC/TAF to DOR/ISL compared with continued BIC/FTC/TAF, as assessed by review of the safety data accumulated through Week 48

Secondary objectives 5

1. To evaluate the antiretroviral activity of a switch to DOR/ISL compared with continued BIC/FTC/TAF, as assessed by the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96
2. To evaluate the antiretroviral activity of a switch to DOR/ISL compared with continued BIC/FTC/TAF, as assessed by the percentage of participants with the following at Week 48 and Week 96: - HIV-1 RNA <200 copies/mL - HIV-1 RNA <50 copies/mL
3. To evaluate the immunologic effect of a switch to DOR/ISL compared with continued BIC/FTC/TAF, as assessed by the mean change from baseline in CD4+ T-cell count at Week 48 and Week 96
4. To evaluate the development of viral drug resistance to any study intervention at Week 48 and Week 96
5. To evaluate the safety and tolerability of a switch from BIC/FTC/TAF to DOR/ISL compared with continued BIC/FTC/TAF, as assessed by review of the safety data accumulated through study duration

Conditions and MedDRA coding

HIV-1 infection

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Participants ≥18 years of age
2. Is HIV-1 positive with plasma HIV-1 RNA <50 copies/mL
3. Has been receiving BIC/FTC/TAF therapy with documented viral suppression (HIV-1 RNA <50 copies/mL) for ≥3 consecutive months prior to providing documented informed consent and has no history of prior virologic treatment failure on any past or current regimen
4. Female is not a participant of childbearing potential (POCBP); or if a participant of childbearing potential, not pregnant or breastfeeding, and is willing to use an acceptable contraceptive method or abstain from heterosexual intercourse for study duration

Exclusion criteria 9

1. Has HIV-2 infection
2. Has a diagnosis of an active acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 30 days prior to screening
3. Has active hepatitis B virus (HBV) infection
4. Has chronic hepatitis C virus (HCV) infection with laboratory values consistent with cirrhosis
5. Has a history of malignancy ≤5 years prior to providing documented informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or cutaneous Kaposi’s sarcoma
6. Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or strong and moderate cytochrome P450 3A (CYP3A) inducers
7. Has a documented or known virologic resistance to DOR
8. Has taken long-acting HIV therapy at any time (e.g., cabotegravir, lenacapavir)
9. Is currently participating in or has participated in a clinical study and received (or is receiving) an investigational compound or device from 45 days prior to Day 1 through the study treatment period except those currently enrolled in the comparator arm of an ongoing DOR/ISL study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Percentage of participants with human immunodeficiency virus type-1 (HIV-1) ribonucleic acid (RNA) ≥50 copies/mL at Week 48
2. Percentage of participants who experience adverse events (AEs) through Week 48
3. Percentage of participants who discontinue study intervention due to AEs through Week 48

Secondary endpoints 11

1. Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96
2. Percentage of participants with HIV-1 RNA <200 copies/mL at Week 48
3. Percentage of participants with HIV-1 RNA <50 copies/mL at Week 48
4. Percentage of participants with HIV-1 RNA <200 copies/mL at Week 96
5. Percentage of participants with HIV-1 RNA <50 copies/mL at Week 96
6. Change from baseline in CD4+ T-cell count at Week 48
7. Change from baseline in CD4+ T-cell count at Week 96
8. Number of participants with viral drug resistance mutations at Week 48
9. Number of participants with viral drug resistance mutations at Week 96
10. Percentage of participants who experience AEs through study duration
11. Percentage of participants who discontinue study intervention due to AEs through study duration

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Michelle Fox

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Michelle Fox

Third parties 6

Locations

4 EU/EEA countries · 31 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications