Efficacy of doravirine + dolutegravir dual therapy in the context of antiretroviral therapy switch

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Chelsea And Westminster Hospital NHS Foundation Trust

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

27 Feb 2025 → ongoing

Decision date (initial)

2024-11-29

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck, Sharp and Dohme Inc

External identifiers

EU CT number

2023-509751-14-03

ClinicalTrials.gov

NCT04892654

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of switching from suppressive triple cART to doravirine and dolutegravir dual cART in PLWH on ART with an undetectable viral load.

Secondary objectives 3

1. To evaluate over 96 weeks: 1. The safety and tolerability of switch from suppressive triple cART to doravirine and dolutegravir dual cART.
2. Patient reported outcomes including quality of life and HIV symptom index.
3. Comparison of control and switch arms in: a) CD4 and CD4:8 ratio b) Lipids & estimated cardiovascular risk changes c) Waist circumference and Weight/BMI changes

Conditions and MedDRA coding

HIV

Regulatory references

Plan to share IPD

No

IPD plan description

Individual persona identifiable data will not be shared by the recruiting site with Sponsor or funder. Clinical trial data will be share using unique trial number which will be unique to each participant. Only clinical data with trial ID will be shared with Sponsor for final data analysis.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. HIV-1 infected, 18 years or older
2. On stable & suppressive triple cART for at least 6 months (this can include DOR and/or DTG)
3. No evidence of resistance to DOR or DTG (INSTI mutations that will lead to the need of administering DTG twice-daily are considered as resistance to DTG)
4. No laboratory abnormalities, medical/psychiatric conditions or alcohol/drug use considered a barrier to participation by investigators
5. Women who are of childbearing potential (WOCBP) and sexually active need to use the hormonal contraceptive methods, associated with inhibition of ovulation: 1. Implant 2. Progesterone injection 3. Intra-uterine device or system 4. Oral hormonal contraception
6. Men who are sexually active and have partners who are women of childbearing potential must be using an adequate method of contraception to avoid pregnancy (male condom or sterilisation confirmed prior to the subject’s entry into the study)

Exclusion criteria 13

1. History of virological failure on an NNRTI in absence of a post-failure genotypic resistance test proving absence of resistance to DOR
2. History of virological failure on an INSTI in absence of a post-failure genotypic resistance test proving absence of resistance to DTG (INSTI mutations that will lead to the need of administering DTG twice-daily are considered as resistance to DTG – and the subject will be considered NOT eligible)
3. Concomitant medication contra-indicated with DTG or DOR
4. Haemoglobin <9 g/dL
5. Platelets <80,000/mm3
6. Creatinine clearance <30 mL/min
7. AST or ALT ≥5N
8. Acute Hepatitis A infection
9. Concomitant DAA for anti-HCV therapy
10. Known acute or chronic viral hepatitis B or C. Exceptions: 1. Individuals testing positive for HBcAb, but negative HBsAg/HBeAg, may be included on the trial. 2. Individuals with positive anti-HCV results, but with HCV RNA not detected may be included on the trial.
11. Pregnant or breastfeeding women
12. Hypersensitivity to the active substance or to any of the excipients in the dolutegravir and/or doravirine formulations
13. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint will be a comparison of the percentage of participants in each treatment arm with undetectable plasma HIV RNA levels at week 48. Undetectable will be defined as plasma RNA levels of <50 copies/ml. Any patient with HIV RNA levels >50 copies/ml at analysis time points will have a repeat test. If the result from the repeat test is below 50 copies/ml the participant will be classified as a responder.

Secondary endpoints 5

1. Absolute efficacy of study treatments: Proportion of patients treated on each arm with HIV viral load <50 copies/ml at weeks 24,72,96.
2. Safety and tolerability: 1 Occurrence of adverse events (including laboratory results), severity of adverse events and occurrence of treatment discontinuations due to tolerability of treatments.
3. Safety and tolerability- 2. Changes in CD4 count and CD4:CD8 ratio at screening, weeks 24, 48, 72 and 96
4. Safety and tolerability - 3. Occurrences and details of viral resistance in study participants
5. Safety and tolerability- 4. Scores from participant-recorded outcome measures at weeks 0, 24, 48, 72 and 96: • EuroQoL Questionnaire • Patient Treatment Satisfaction Questionnaire • Pittsburgh Sleep Questionnaire

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Chelsea And Westminster Hospital NHS Foundation Trust

Sponsor organisation

Chelsea And Westminster Hospital NHS Foundation Trust

Address

369 Fulham Road

City

London

Postcode

SW10 9NH

Country

United Kingdom

Scientific contact point

Organisation

Chelsea And Westminster Hospital NHS Foundation Trust

Contact name

Manisha Joshi

Public contact point

Organisation

Chelsea And Westminster Hospital NHS Foundation Trust

Contact name

Manisha Joshi

Locations

1 EU/EEA country · 1 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 23 files

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

Application history

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