A Randomised, Phase 3 Non-inferiority Study of DOR/3TC/TDF Compared to DTG/TAF/FTC in Participants Infected With HIV-1 Starting First-line Antiretroviral Therapy

NCT05924438 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: EZ-JW-033DOH-27-052023-5232
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, randomised, phase 3, two-arm study conducted over 96 weeks. The study includes a screening period day - 60 to -1, enrolment visit day 0, and a 96-week treatment follow-up period. Approximately 600 male and female participants infected with HIV-1 eligible for first-line therapy, will be randomly assigned in a 1:1 ratio approximately 300 participants per treatment group to either Treatment Group 1 DOR/3TC/TDF or Treatment Group 2 DTG/TAF/FTC. All medications will be administered in an open label design.

Conditions

HIV-1-infection

Keywords

delstrigo; KOCITAF; doravirine; HIV-1 RNA; dolutegravir; weight gain

Outcome Measures

Primary Outcomes (1)

• The antiretroviral activity of DOR/3TC/TDF compared to DTG/TAF/FTC in the first line treatment, as assessed by the percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48

  HIV1-RNA

  48 Weeks

Secondary Outcomes (11)

• The antiretroviral activity of DOR/3TC/TDF compared to DTG/TAF/FTC, as assessed by the percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96

  96 Weeks

• The antiretroviral activity of DOR/3TC/TDF compared with DTG/TAF/FTC, as assessed by the percentage of participants with HIV-1 RNA <200 copies/mL at Week 48 and Week 96

  48 and 96 Weeks

• Time to virologic failure (defined as confirmed HIV-1 RNA levels ≥ 1000 copies/mL at week 24 or ≥ 200 copies/mL after week 24)

  24 Weeks

• The immunologic effect of DOR/3TC/TDF compared with DTG/TAF/FTC, as assessed by the mean change from baseline in CD4+ T-cell count at Week 48 and Week 96

  48 and 96 Weeks

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

  96 Weeks

Other Outcomes (6)

• To evaluate the pharmacokinetics of DOR in pregnant women

  96 Weeks

• Number of pregnant women with treatment related adverse events as assessed by (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events v2.1

  96 Weeks

• To describe Patient-Reported Outcomes (PROs) for participants who received DOR/3TC/TDF compared with DTG/TAF/FTC overtime

  96 Weeks

Study Arms (2)

Treatment Group 1

EXPERIMENTAL

Delstrigo

Drug: Delstrigo

Treatment Group 2

OTHER

KOCITAF

Drug: KOCITAF

Interventions

Delstrigo DRUG

Treatment Group 1 Participants will receive Doravirine, as part of a fixed-dose oral combination with lamivudine and tenofovir disoproxil fumarate (DOR/3TC/TDF, Delstrigo)tablets which are to be administered orally and once daily.

Treatment Group 1

KOCITAF DRUG

Treatment Group 2 Participants will receive dolutegravir, as part of a fixed-dose oral combination with tenofovir alafenamide plus emtricitabine (DTG/TAF/FTC, KOCITAF) tablets which are to be administered orally and once daily.

Treatment Group 2

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Each participant must meet all the following criteria to be enrolled in this study.
• ≥18 years old, male or female.
• Documented laboratory diagnosis of infection with HIV-1 (positive enzyme-linked immunosorbent assay HIV-1 antibody test) at screening, with no baseline DOR resistance (please see Table 2 below).
• Is ART naïve.
• BMI≥ 25 kg/cm2.
• VL \>500 copies/ml.
• Must sign an ICF indicating that he or she understands the purpose of, and procedures required for the study and is willing to participate in the study.
• Female participants of childbearing potential (WOCBP) are eligible to participate if willing to use highly effective contraception methods from enrolment, for the duration of the study.

You may not qualify if:

• Participants meeting any of the following criteria will be excluded from the study:
• Is currently participating in any other interventional study or participated in a study with an investigational drug within 60 days of screening.
• Is pregnant, breastfeeding or intends to become pregnant or breastfeed during the study.
• Has active TB co-infection and requires anti-TB treatment.
• Has unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypalbuminaemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones); Child-Pugh C.
• Has pre-existing physical or mental condition (including substance abuse disorder and suicide risk) which, in the opinion of the Investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
• Clinically unstable in the investigator's opinion (any pre-existing medical or laboratory abnormalities must be deemed to be stable by the investigator prior to study enrolment).
• Has estimated creatinine clearance \<60mL/min per Cockcroft-Gault formula.
• Is taking, and is unable to discontinue, any of the following prohibited medications: carbamazepine, oxcarbazepine, phenobarbital, phenytoin; the antimycobacterial rifampicin, rifapentine; St. John's Wort (Hypericum perforatum); mitotane; enzalutamide; lumacaftor.

Sponsors & Collaborators

• Professor Francois Venter: lead
• Africa Health Research Institute: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Ezintsha Research Centre

Johannesburg, Gauteng, 2193, South Africa

Location

MeSH Terms

Conditions

Weight Gain

Condition Hierarchy (Ancestors)

Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• JOANA FRANCISCA WOODS, MBBCh

  Ezintsha Resesarch Centre

  PRINCIPAL INVESTIGATOR

• SIMISO MANDISA Sokhela, MBBCh

  Ezintsha Research Centre

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 23, 2023
• First Posted: June 29, 2023
• Study Start: November 8, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Immediately following publication

Locations

ZA (1)