Clinical trial NCT05495204: External Comparison of Ibalizumab in Trials vs. Other Regimens in OPERA
Official title: External Comparison of Effectiveness of Ibalizumab in Clinical Trials vs. Other HTE Regimens in OPERA
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV-1-infection
Keywords: Heavily treatment experienced
External comparison
Ibalizumab
Virologic effectiveness
Lead sponsor: Epividian
Sponsor class: INDUSTRY
Collaborators: name: Theratechnologies
name: FIECON
First posted: 2022-08-10
Enrollment: 141
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All TMB-202 and TMB-301/311 trial participants randomized to 800 mg IBA every 2 weeks with or without a loading dose will be included in the main analyses. From the OPERA cohort, adult PWH with resistance from three ARV classes will be considered for inclusion. People with HIV in OPERA initiating a new non-IBA OBR between 01JAN2008 and 31DEC2020 will be included; person-time will be censored at the first of (a) initiation of a select potent ARV, (b) \>45 days without ART, (c) 12 months after last clinical contact, (d) death, or (e) study end.

Brief summary: Among heavily treatment experienced people living with HIV, the virologic effectiveness of ibalizumab + optimized background regimen from two clinical trials will be compared to non-ibalizumab-containing regimens in routine clinical care in the OPERA cohort.

Detailed description: The US Department of Health and Human Services (DHHS) HIV treatment guideline suggest that ibalizumab may be considered in the context of multidrug resistance without fully active ART options. However, clinical trials assessing ibalizumab efficacy did not include an active comparison arm in which participants did not receive ibalizumab. The use of external controls can provide valuable information and context to interpret the results of clinical trials when randomization to a control arm cannot be performed.

The OPERA (Observational Pharmaco-Epidemiology Research \& Analysis) cohort, a large US electronic health record database, is well suited for this as the OPERA and trials populations arose from the same geographic location (i.e., US). An external comparison of ibalizumab + optimized background regimen from trials vs. non-ibalizumab containing regimens in routine clinical care in the OPERA cohort may confirm results from prior studies suggesting viral control benefits of ibalizumab.

Eligibility criteria: Inclusion Criteria (Trial IBA+OBR group):

* Participant in TMB-202 or TMB-301/311
* Received 800 mg IBA every 2 weeks, with or without a loading dose

Inclusion Criteria (OPERA non-IBA OBR group):

* HIV-1 infection
* 18 years or older
* Heavily treatment experienced (i.e., ever on a regimen containing either DTG BID or DRV BID)
* Documented resistance to ≥1 ARV from each of three ARV classes
* Genotype information available for all the relevant gene regions (see Table 2)
* Viral load \> 200 copies/mL at index regimen initiation
* Not pregnant at index
* No new AIDS defining event within 3 months before/on index (except cutaneous Kaposi's sarcoma or HIVAW)
* No new cancer diagnosis within 12 weeks before/on index
* No IBA prescribed prior to/with the index regimen
* Index regimen does not include cabotegravir, fostemsavir, investigational drugs
* Viral sensitivity/susceptibility to at least one ARV in the index regimen
* Baseline VL available (within 6 months before/at index)
* Baseline CD4 available (within 6 months before/at index)
* ≥1 VL measurement at any time after index

Primary outcomes:
measure: Viral suppression
timeFrame: Week 24
measure: Viral suppression
timeFrame: Week 48
measure: Viral suppression
timeFrame: Week 60
measure: Viral suppression
timeFrame: Week 96
measure: Viral undetectability
timeFrame: Week 24
measure: Viral undetectability
timeFrame: Week 48
measure: Viral undetectability
timeFrame: Week 60
measure: Viral undetectability
timeFrame: Week 96
Secondary outcomes:
Other outcomes:
Locations:
city: Durham
country: United States
facility: Epividian
state: North Carolina
Study officials:
References: