External Comparison of Ibalizumab in Trials vs. Other Regimens in OPERA

External Comparison of Effectiveness of Ibalizumab in Clinical Trials vs. Other HTE Regimens in OPERA

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.

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: Ibalizumab

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.

• Study Type: Observational
• Enrollment (Actual): 141

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27703
      • Epividian

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Other

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
IBA+OBR (trials); Participants in TMB-202 or TMB-301/311 trials who received 800 mg ibalizumab every 2 weeks, with or without a loading dose	Drug: Ibalizumab; Participation in clinical trials vs. routine care in OPERA; Other Names: Regimens not containing ibalizumab
Non-IBA+OBR (OPERA); Heavily treatment experienced adults living with HIV in care in OPERA, with documented resistance to ≥1 ARV from each of three ARV classes switching to a new regimen that does not include ibalizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral suppression	Viral load <200 copies/mL	Week 24
Viral suppression	Viral load <200 copies/mL	Week 48
Viral suppression	Viral load <200 copies/mL	Week 60
Viral suppression	Viral load <200 copies/mL	Week 96
Viral undetectability	Viral load <50 copies/mL	Week 24
Viral undetectability	Viral load <50 copies/mL	Week 48
Viral undetectability	Viral load <50 copies/mL	Week 60
Viral undetectability	Viral load <50 copies/mL	Week 96

Collaborators and Investigators

• Sponsor: Epividian
• Collaborators: Theratechnologies; FIECON

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2022
• Primary Completion (Actual): February 20, 2023
• Study Completion (Actual): February 20, 2023

Study Registration Dates

• First Submitted: August 5, 2022
• First Submitted That Met QC Criteria: August 8, 2022
• First Posted (Actual): August 10, 2022

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: September 5, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Heavily treatment experienced; External comparison; Ibalizumab; Virologic effectiveness
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Immunologic Factors; Antibodies, Monoclonal; Ibalizumab
• Other Study ID Numbers: COL2022-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No