A clinical study of people with HIV-1 who have not taken antiretroviral therapy, one group will start treatment with a combination of doravirine and Islatravir compared to a different group that will start treatment with bictegravir/emtricitabine/tenofovir alafenamide

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]

Trial duration

29 Apr 2024 → ongoing

Decision date (initial)

2024-03-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-502099-22-01

WHO UTN

U1111-1283-2516

ClinicalTrials.gov

NCT05705349

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

1. To evaluate the antiretroviral activity of DOR/ISL compared to 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 DOR/ISL compared with BIC/FTC/TAF as assessed by review of the accumulated safety data through Week 48.

Secondary objectives 6

1. To evaluate the antiretroviral activity of DOR/ISL compared with BIC/FTC/TAF, as assessed by the percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 and Week 144
2. To evaluate the antiretroviral activity of DOR/ISL compared with BIC/FTC/TAF, as assessed by the percentage of participants with HIV-1 RNA <200 copies/mL at Week 48, Week 96, and Week 144
3. To evaluate the immunologic effect of DOR/ISL compared with BIC/FTC/TAF, as assessed by the mean change from baseline in CD4+ T-cell count at Week 48, Week 96, and Week 144
4. To evaluate the development of viral drug resistance in participants who receive DOR/ISL and in those who receive BIC/FTC/TAF
5. To evaluate the effect of DOR/ISL compared with BIC/FTC/TAF on weight, as assessed by the mean change from baseline to Week 48, Week 96, and Week 144.
6. To evaluate the safety and tolerability of DOR/ISL compared with BIC/FTC/TAF as assessed by review of the accumulated safety data through Week 144.

Conditions and MedDRA coding

HIV-1 Infection

Study design 1 period

Regulatory references

Scientific advice from competent authorities

National Agency For The Safety Of Medicine And Health Products, Federal Institute For Drugs And Medical Devices, European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Is an individual ≥18 years of age of any sex/gender who is HIV-1 positive with plasma HIV-1 RNA ≥500 copies/mL at screening
2. Is naïve to antiretroviral therapy (ART) defined as having received no prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection
3. Female is not a participant of childbearing potential (POCBP); or if a POCBP, is not pregnant or breastfeeding, and is willing to use an acceptable contraceptive method or abstain from heterosexual intercourse for study duration

Exclusion criteria 7

1. Has 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 AIDS-defining opportunistic infection within 30 days prior to screening
4. Has active hepatitis B infection (defined as hepatitis B surface antigen [HBsAg]-positive or HBV deoxyribonucleic acid [DNA]-positive).
5. Has chronic hepatitis C virus (HCV) infection (detectable HCV ribonucleic acid [RNA])
6. 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
7. 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, such that it is not in the best interest of the participant to participate

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 experiencing ≥1 adverse event (AE) through Week 48
3. Percentage of participants discontinuing from study treatment due to an AE through Week 48

Secondary endpoints 14

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 <200 copies/mL at Week 96
4. Change from baseline in cluster of differentiation 4+ (CD4+) T-cells at Week 48
5. Change from baseline in CD4+ T-cells at Week 96
6. Incidence of viral drug resistance
7. Change from baseline in body weight at Week 48
8. Change from baseline in body weight at Week 96
9. Percentage of participants experiencing ≥1 AE through Week 96
10. Percentage of participants discontinuing from study treatment due to an AE through Week 48
11. Percentage of participants with HIV-1 RNA <50 copies/mL at Week 144
12. Percentage of participants with HIV-1 RNA <200 copies/mL at Week 144.
13. Change from baseline in CD4+ T-cells at Week 144.
14. Change from baseline in body weight at Week 144

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

Mary Pisculli

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Mary Pisculli

Third parties 4

Locations

3 EU/EEA countries · 23 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 45 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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