A clinical study of people with HIV-1 who take antiretroviral therapy and 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)

2023-04-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-502127-22-00

WHO UTN

U1111-1283-3894

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

1. To evaluate the antiretroviral activity of a switch to Doravirine/Islatravir (DOR/ISL) compared with continued baseline antiretroviral therapy (ART), as assessed by the percentage of participants with human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) ≥50 copies/mL at Week 48
2. To evaluate the safety and tolerability of a switch to DOR/ISL compared with continued baseline ART, as assessed by review of the safety data accumulated

Secondary objectives 8

1. To evaluate the antiretroviral activity of a switch to DOR/ISL compared with continued baseline ART, as assessed by the percentage of participants with the following at Week 48: HIV-1 RNA <200 copies/mL, HIV-1 RNA <50 copies/mL
2. To evaluate the antiretroviral activity of a switch to DOR/ISL in participants who continued baseline ART and switched to DOR/ISL at Week 48, as assessed by the percentage of participants with the following at Week 96: HIV-1 RNA ≥50 copies/mL, HIV-1 RNA <200 copies/mL, HIV-1 RNA <50 copies/mL
3. To evaluate the antiretroviral activity of a switch to DOR/ISL in participants who switched from baseline ART to DOR/ISL on Day 1, as assessed by the percentage of participants with the following at Week 96: HIV-1 RNA ≥50 copies/mL, HIV-1 RNA <200 copies/mL, HIV-1 RNA <50 copies/mL
4. To evaluate the immunologic effect of a switch to DOR/ISL compared with continued baseline ART, as assessed by the mean change from baseline in cluster of differentiation 4+ (CD4+)T-cell count at Week 48
5. To evaluate the immunologic effect of a switch to DOR/ISL, as assessed by the mean change in CD4+ T-cell count: from baseline (Day 1) to Week 96 and from Week 48 to Week 96 in participants who switched from baseline ART to DOR/ISL on Day 1; and from Week 48 to Week 96 in participants who continued baseline ART and switched to DOR/ISL at Week 48
6. To evaluate the development of viral drug resistance to any study intervention at Week 48 and Week 96
7. To evaluate the effect on fasting low density lipoprotein cholesterol (LDL-C) and non- high density lipoprotein cholesterol (non-HDL-C) of a switch to DOR/ISL compared with continued baseline ART by baseline ART class (protease inhibitor (PI) -containing regimens [including PI- + integrase strand transfer inhibitor (InSTI)-containing regimens], InSTI-containing regimens [non-PI-containing regimens], and non-PI- and non-InSTI-containing regimens), as assessed by the mean change in fasting LDL-C and non-HDLC from baseline to Week 48
8. To evaluate the safety and tolerability of a switch to DOR/ISL compared with continued baseline ART, as assessed by review of the safety data accumulated through Week 96: from baseline (Day 1) through Week 96 and from Week 48 through Week 96 in participants who switched from baseline ART to DOR/ISL on Day 1; and from Week 48 through Week 96 in participants who continued baseline ART and switched to DOR/ISL at Week 48

Conditions and MedDRA coding

HIV-1 Infection

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Is HIV-1 positive with plasma HIV-1 RNA <50 copies/mL at screening
2. Has been receiving continuous, stable oral 2-drug or 3-drug combination (± pharmacokinetic (PK) booster) ART 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
3. Female is not a participant of childbearing potential (POCBP); or if a POCBP uses an acceptable contraceptive method or abstains from penile-vaginal intercourse as their preferred and usual lifestyle; has a negative highly sensitive pregnancy test; and whose medical history, menstrual history, and recent sexual activity has been reviewed by the investigator

Exclusion criteria 10

1. Has human immunodeficiency virus type 2 (HIV-2) infection
2. Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
3. Has a diagnosis of an active acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 30 days prior to screening
4. Has active hepatitis B virus (HBV) infection
5. Has chronic hepatitis C virus (HCV) infection consistent with cirrhosis
6. Has a ≤5 years prior history of malignancy
7. Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or strong and moderate cytochrome P450 3A (CYP3A) inducers
8. Has taken long-acting HIV therapy at any time
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
10. Has a documented or known virologic resistance to DOR

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48
2. Percentage of participants with one or more adverse events (AEs) from Day 1 up to Week 48
3. Percentage of participants with an AE leading to discontinuation of study intervention from Day 1 up to Week 48

Secondary endpoints 15

1. Percentage of participants with HIV-1 RNA <200 copies/mL at Week 48
2. Percentage of participants with HIV-1 RNA <50 copies/mL at Week 48
3. Percentage of participants with HIV-1 RNA <200 copies/mL at Week 96
4. Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96
5. Percentage of participants with HIV-1 RNA <50 copies/mL at Week 96
6. Mean change from baseline at Day 1 in CD4+ T-cell count at Week 48
7. Mean change from baseline at Week 48 in CD4+ T-cell count at Week 96
8. Mean change from baseline at Day 1 in CD4+ T-cell count at Week 96
9. Number of participants with viral resistance-associated substitutions
10. Mean change from baseline to Week 48 in fasting LDL-C
11. Mean change from baseline to Week 48 in fasting HDL-C
12. Percentage of participants with one or more AEs from Day 1 up to Week 96
13. Percentage of participants with an AE leading to discontinuation of study intervention from Day 1 up to Week 96
14. Percentage of participants with one or more AEs from Week 48 up to Week 96
15. Percentage of participants with an AE leading to discontinuation of study intervention from Week 48 up to Week 96

Investigational products

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

Test 1

Comparator 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

Jason Yun Kim

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Jason Yun Kim

Third parties 6

Locations

3 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Application history

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