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iHEART-SA

DOR/ISL 100 mg/0.25 mg QD Open-Label Switch

Projects

A Phase 3, Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL 100 mg/0.25 mg) Once-Daily in Participants With HIV-1 Who Are Virologically Suppressed on Antiretroviral Therapy

 

Hypotheses, Objectives, and Endpoints:

Hypotheses are aligned with objectives in the Objectives and Endpoints table.

The following objectives will be evaluated in participants ≥18 years of age with HIV-1 who have been virologically suppressed (ie, HIV-1 RNA <50 copies/mL) for ≥3 consecutive months on a stable oral 2- or 3-drug combination (± PK booster) ART.

 

Objectives Endpoints
Primary
  • To evaluate the antiretroviral activity of a switch to DOR/ISL compared with
    continued baseline ART, as assessed by the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48
  • Hypothesis (H1): DOR/ISL is noninferior to continued baseline ART, as assessed by the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48. A margin of 4 percentage points is used to define non-inferiority.
  • HIV-1 RNA
  • 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 48
  • Adverse events
  • Adverse events leading to discontinuation of study intervention

 

Objectives Endpoints
Secondary
  • 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
  • HIV-1 RNA
  • 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
  • HIV-1 RNA
  • 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
  • HIV-1 RNA
  • 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 CD4+ T-cell count at
    Week 48
  • CD4+ T-cell count
Objectives Endpoints
  • 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
    • From Week 48 to Week 96 in participants who continued baseline ART and switched to
      DOR/ISL at Week 48
  • CD4+ T-cell count
  • To evaluate the development of viral drug resistance to any study intervention
    at Week 48 and Week 96
  • Viral resistance-associated substitutions
  • To evaluate the effect on fasting LDL-C and non-HDL-C of a switch to DOR/ISL compared with
    continued baseline ART by baseline ART class (PI-containing regimens [including PI- +
    InSTIcontaining 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

    • If non-inferiority of DOR/ISL to continued baseline ART at Week 48 (H1) is met, the
      following hypothesis will be tested for each parameter within each stratum
  • Hypothesis (H2): DOR/ISL is superior to continued baseline ART in each baseline
    ART stratum (in
    the order of: PIcontaining regimens [including PI- + InSTI-containing regimens], non-PI- and
    non-InSTI-containing regimens, and InSTI-containing regimens [non- PIcontaining regimens]), as
    assessed by the mean change from baseline in fasting LDL-C and non-HDL-C at Week 48.
  • Fasting LDL-C and non-HDL-C
  • 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
    • From Week 48 through Week 96 in participants who continued baseline ART and switched to
      DOR/ISL at Week 48
  • Adverse events
  • Adverse events leading to discontinuation of study intervention

Overall Design:

Study Phase Phase 3
Primary Purpose Treatment
Indication HIV-1 Infection
Population Participants ≥18 years of age with HIV-1 who have been virologically suppressed for ≥3 consecutive
months on a stable oral 2-drug or 3-drug combination (± PK booster) ART
Study Type Interventional
Intervention Model Parallel
This is a multi-site study.
Type of Control Active Control
Study Blinding Unblinded Open-label
Blinding Roles No Blinding
Estimated Duration of Study The Sponsor estimates that the study will require approximately 2.5 years from the time the first
participant (or their legally acceptable representative) provides documented informed consent until the
last participant’s last study-related contact.
Intervention Groups
Intervention Group Name Drug Dose Strength Dose Frequency Route of Administration Treatment Period Use
Group 1 doravirine/ islatravir 100 mg doravirine/ 0.25 mg
islatravir		 QD Oral Day 1 to Week 96 Test Product
Group 2 Baseline antiretroviral therapy regimen Per local requirements Day 1 to Week 48 Comparator
doravirine/ islatravir 100 mg doravirine/ 0.25 mg islatravir QD Oral Week 48 to Week 96 Test Product
QD=once-daily. new

Allowed drug classes for baseline ART regimen include NRTIs, NNRTIs, PIs, InSTIs, and PK boosters.

The Sponsor will not provide baseline ART medications for participants continuing their baseline ART regimens. Participants will provide their own ART medications, in accordance with local regulations.

Study intervention will be extended for participants who become pregnant on treatment and provide documented informed consent to continue their study intervention (DOR/ISL or baseline ART), as specified in
Sections 1.3.4 and 8.11.6.

Total Number of Intervention Groups/ Arms 2
Duration of Participation Each participant will participate in the study for approximately 2 years from the time the participant
provides documented informed consent through the final contact. After a screening phase of up to 45
days, each participant will receive the assigned open-label study intervention for approximately 48
weeks. After 48 weeks of the assigned therapy, all participants will receive open-label DOR/ISL through
Week 96. Participants who discontinue study intervention or who become pregnant will be followed as
described in the protocol.
#1293
The study utilises a cross-sectional design to investigate obstructive sleep apnoea (OSA) among adult people living with HIV (PLWH).

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