Ibalizumab Plus Optimized Background Regimen in Treatment-Experienced Patients With Multi-Drug Resistant HIV-1

NCT02707861 | Completed Phase 3 Results

• 1 other identifier: TMB-311
• Study Type: interventional
• Target: 79
• Locations: 2 countries
• Sites: 32

Brief Summary

Ibalizumab is a monoclonal antibody that works by blocking HIV entry into the immune system cells (CD4+ or T-cells) the virus typically infects. Ibalizumab is intended for use in combination with other anti-HIV drugs in people with multi-drug resistant HIV and limited treatment options. This study will collect further information on the safety and tolerability of intravenously administered (IV) ibalizumab combined with an optimized background regimen for treating multi-drug resistant HIV-1 infection, and will provide continuing access to ibalizumab for patients completing a prior ibalizumab clinical trial.

Conditions

HIV

Keywords

HIV; Resistant; Salvage; ibalizumab; antibody; AIDS

Outcome Measures

Primary Outcomes (3)

• Safety and Tolerability of Ibalizumab + OBR

  Number of participants with Grade 3/4 adverse events possibly, probably, or definitely due to ibalizumab

  Through 48 weeks

• Discontinuations Due to Adverse Events Related to Ibalizumab

  number of participants discontinuing ibalizumab treatment due to adverse events probably, possibly, or definitely related to ibalizumab

  48 weeks

• Effectiveness of Ibalizumab + OBR (Cohort 2 Only)

  Number of patients in Cohort 2 achieving at least a 0.5 log change from Baseline in viral load at Day 7 of the study

  7 days

Secondary Outcomes (3)

• Suppression to <50 Copies With Ibalizumab + OBR (Cohort 2 Only)

  48 weeks

• Suppression to <400 Copies by Ibalizumab + OBR (Cohort 2 Only)

  48 weeks

• Effectiveness of Ibalizumab + OBR by 1.0 Log10 Decrease in Viral Load From Baseline (Cohort 2 Only)

  48 weeks

Study Arms (2)

Cohort 1

EXPERIMENTAL

IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial OR 2000 mg once every four weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial Administered for 48 weeks, or until ibalizumab becomes commercially available

Drug: ibalizumab; Drug: Optimized Background Regimen

Cohort 2

EXPERIMENTAL

IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for qualifying patients who have never received ibalizumab Administered for 48 weeks, or until ibalizumab becomes commercially available

Drug: ibalizumab; Drug: Optimized Background Regimen

Interventions

ibalizumab DRUG

Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry

Also known as: TNX-355, Hu5A8

Cohort 1; Cohort 2

Optimized Background Regimen DRUG

An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).

Also known as: antiretroviral therapy

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (Cohort 1)
• Currently receiving ibalizumab via other TaiMed-sponsored or investigator-Sponsored protocol
• Are capable of understanding and have voluntarily signed the informed consent document
• (Cohort 2)
• years of age or older
• Are capable of understanding and have voluntarily signed the informed consent document
• Have documented HIV-1 infection by official, signed, written history (e.g., laboratory report), otherwise an HIV-antibody test will be performed
• Are able and willing to comply with all protocol requirements and procedures
• Have a viral load \>1,000 copies/mL and documented resistance to at least one antiretroviral medication from each of three classes of antiretroviral medications as measured by previous viral resistance testing (resistance testing is not provided by the study for qualification purposes)
• Have a history of at least 6 months on antiretroviral treatment
• Are receiving a failing antiretroviral regimen OR have failed and are off therapy
• Have viral sensitivity/susceptibility to at least one antiretroviral agent, other than ibalizumab, as determined by previous resistance test performed within 6 months of screening and be willing and able to be treated with at least one agent to which the patient's viral isolate is fully sensitive/susceptible according to the resistance tests used for screening as a component of OBR
• If sexually active, are willing to use an effective method of contraception during the study and for 30 days after the last administration of the study drug

You may not qualify if:

• (Cohort 1)
• (Cohort 2)
• Eligible for participation in other TaiMed-sponsored clinical trials of ibalizumab
• Any significant diseases (other than HIV-1 infection) or clinically significant findings, including psychiatric and behavioral problems, determined from screening, medical history and/or physical examination that, in the investigator's opinion, would preclude the patient from participating in this study
• Any significant acute illness within 1 week before the first administration of investigational medication on this study
• Any active infection secondary to HIV requiring acute therapy; however, patients that require maintenance therapy (i.e., secondary prophylaxis for opportunistic infections) will be eligible for the study.
• Any immunomodulating therapy (including interferon), systemic steroids, or systemic chemotherapy within 4 weeks before Day 0
• Any prior exposure to ibalizumab (formerly TNX-355 and Hu5A8)
• Any vaccination within 7 days before Day 0
• Any female patient who either is pregnant, intends to become pregnant, or is currently breastfeeding
• Any current alcohol or illicit drug use that, in the investigator's opinion, will interfere with the patient's ability to comply with the study schedule and protocol evaluations
• Any previous clinically significant allergy or hypersensitivity to any excipient in the ibalizumab formulation
• Any radiation therapy during the 28 days before first administration of investigational medication on this study
• Any clinically significant Grade 3 or 4 laboratory abnormality according to the Division of AIDS (DAIDS) grading scale, except for the following asymptomatic Grade 3 events:
• triglyceride elevation

Sponsors & Collaborators

• TaiMed Biologics Inc.: lead
• Westat: collaborator

Study Sites (32)

Long Beach Education and Research Consultants

Long Beach, California, 90813, United States

Location

Southern California Permanente Medical Group

Los Angeles, California, 90027, United States

Location

Ruane Clinical Research Institute Inc.

Los Angeles, California, 90036, United States

Location

Charles R. Drew University of Medicine and Science, Clinical and Translational Research Center

Los Angeles, California, 90059, United States

Location

Anthony Mills MD Inc.

Los Angeles, California, 90069, United States

Location

Palmtree Clinical Research, Inc.

Palm Springs, California, 92262, United States

Location

eStudy Site

San Francisco, California, 94115, United States

Location

Kaiser Foundation Research Institute

San Francisco, California, 94118, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

Georgetown University School of Medicine

Washington D.C., District of Columbia, 20007, United States

Location

Gary Richmond, MD, PA

Fort Lauderdale, Florida, 33316, United States

Location

AIDS Healthcare Foundation - Kinder Medical Group

Miami, Florida, 33133, United States

Location

AIDS Healthcare Foundation - South Beach

Miami, Florida, 33140, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

Triple O Research Institute

West Palm Beach, Florida, 33401, United States

Location

AIDS Research Consortium of Atlanta

Atlanta, Georgia, 30312, United States

Location

University of Hawaii - John A. Burns School of Medicine

Honolulu, Hawaii, 96813, United States

Location

Howard Brown Health Center

Chicago, Illinois, 60613, United States

Location

National Institute of Allergy & Infectious Diseases

Bethesda, Maryland, 20892, United States

Location

ID Research Institute

Springfield, Massachusetts, 01105, United States

Location

Central West Clinical Research

St Louis, Missouri, 63108, United States

Location

AIDS Healthcare Foundation - Manhattan Midtown HCC

New York, New York, 10001, United States

Location

Chelsea Village Medical

New York, New York, 10011, United States

Location

Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

Philadelphia FIGHT

Philadelphia, Pennsylvania, 19107, United States

Location

St. Jude's Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

St. Hope Foundation Community Health Center

Bellaire, Texas, 77401, United States

Location

North Texas Infectious Disease Consultants

Dallas, Texas, 75246, United States

Location

Crofoot Research Center

Houston, Texas, 77098, United States

Location

Research Access Network

Houston, Texas, 77098, United States

Location

Clinical Research PR, Inc.

San Juan, 00909, Puerto Rico

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

ibalizumab; Antiretroviral Therapy, Highly Active

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Drug Therapy, Combination; Drug Therapy; Therapeutics

Limitations and Caveats

This trial included multiple populations- Cohort 1 included subjects who were treated with ibalizumab and OBR on previous trials including TMB-301, TMB-202, and 2 subjects on expanded access. The Cohort 2 subjects were subjects with MDR resistant virus who were treated with OBR plus ibalizumab. No subjects completed the planned duration of study as the vast majority were switched to commercial supply of drug when the drug was approved by USFDA.

Results Point of Contact

• Title: Manager - Clinical Operations
• Organization: TaiMed Biologics USA Corp.

bbell@taimedbio.com

713-478-2927

Study Officials

• Stanley T. Lewis, MD, MPH

  TaiMed Biologics Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2016
• First Posted: March 14, 2016
• Study Start: March 1, 2016
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2018
• Last Updated: March 11, 2021
• Results First Posted: March 11, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

PR (1); US (31)