Dose-Response Study of Ibalizumab (Monoclonal Antibody) Plus Optimized Background Regimen in Patients With HIV-1

NCT00784147 | Completed Phase 2 Results DMC

• 1 other identifier: TMB-202 Amendment 2
• Study Type: interventional
• Target: 113
• Locations: 2 countries
• Sites: 30

Brief Summary

The investigational product, ibalizumab, is a humanized IgG4 monoclonal antibody administered via intravenous infusion at 800 mg every 2 weeks or at 2000 mg every 4 weeks. In addition to study drug, all patients will receive an optimized background regimen (OBR), which is a standard-of-care regimen selected by the investigator prior to randomization that is comprised of 2-4 antiretroviral agents. These agents must have been approved by the local regulatory agency or be available through expanded-access programs for treatment of human immunodeficiency virus (HIV).

Conditions

HIV

Keywords

HIV; CD4; experienced; resistant; resistance; monoclonal; antibody; infusion; ibalizumab; TNX355; TNX-355; TMB355; TMB-355

Outcome Measures

Primary Outcomes (1)

• The Proportion of Patients Achieving Undetectable Viral Loads at Week 24.

  For the primary efficacy analysis, "undetectable" was defined as having HIV-1 RNA below the limit of assay detection at \<50 copies/mL. The primary efficacy endpoint was analyzed using Fisher exact test. The primary analysis was performed using the ITT population and both the missing data equals treatment failure (MEF) and last observation carried forward (LOCF) methods. The more conservative MEF results are recorded here.

  24 weeks

Secondary Outcomes (2)

• Mean Change From Baseline in Viral Load (log10) at Week 24/EOS

  Week 24 / End of Study

• Mean Change From Baseline in CD4+ T-Cell Count at Week 24/EOS

  Week 24 / End of Study

Other Outcomes (4)

• Proportion of Patients With Viral Load <200 Copies/mL at Week 24

  Week 24

• Proportion of Patients With Viral Load <400 Copies/mL at Week 24

  Week 24

• Proportion of Patients With a 1.0 log10 or Greater Reduction in Viral Load at Week 24

  Week 24

Study Arms (2)

Ibalizumab 800 mg

ACTIVE COMPARATOR

every 2 weeks, combined with an Optimized Background Regimen

Drug: Ibalizumab

Ibalizumab 2000 mg

ACTIVE COMPARATOR

every 4 weeks, combined with an Optimized Background Regimen

Drug: Ibalizumab

Interventions

Ibalizumab DRUG

Ibalizumab 800 mg IV every 2 weeks

Also known as: TNX-355; Hu5A8

Ibalizumab 800 mg

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are capable of understanding and have voluntarily signed the informed consent document
• Have documented HIV-1 infection by official, signed, written history (eg, laboratory report), otherwise an HIV-antibody test will be performed
• Have no acquired immunodeficiency syndrome (AIDS)-defining events in the 3 months before screening, other than cutaneous Kaposi's sarcoma or wasting syndrome due to HIV
• Are able and willing to comply with all protocol requirements and procedures
• Are 18 years of age or older
• Have a life expectancy that is \>6 months.
• Have a viral load \>1,000 copies/mL and documented decreased susceptibility to at least one NRTI, one NNRTI, and one PI, as measured by resistance testing
• Are receiving a stable highly active antiretroviral regimen for at least 8 weeks before screening and are willing to continue that regimen until the baseline visit, OR (in the past 8 weeks) have failed and are off therapy and are willing to stay off therapy until the baseline visit
• Have viral sensitivity/susceptibility to at least one agent (OSS criteria) as determined by the screening resistance tests and be willing and able to be treated with at least one agent to which the patient's viral isolate is sensitive/susceptible according to the screening resistance tests 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:

• Any active AIDS-defining illness per Category C conditions according to the Center for Disease Control (CDC) Classification System for HIV Infection, with the following exceptions: cutaneous Kaposi's sarcoma and wasting syndrome due to HIV
• 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 initial administration of study drug
• Any active infection secondary to HIV requiring acute therapy; however, patients that require maintenance therapy (ie, secondary prophylaxis for opportunistic infections) will be eligible for the study
• Any immunomodulating therapy (including interferon), systemic steroids, or systemic chemotherapy within 12 weeks before randomization
• Any investigational therapy within 30 days before randomization, except for HIV-agents available in expanded-access programs
• Any prior exposure to ibalizumab (formerly TNX-355 and Hu5A8)
• Any vaccination within 21 days before randomization
• Any female patient who either is pregnant, intends to become pregnant, or is currently breast-feeding
• 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
• Any grade 3 or 4 toxicity according to the Division of AIDS grading scale, except for the following asymptomatic grade 3 events: triglyceride elevation \& total cholesterol elevation

Sponsors & Collaborators

• TaiMed Biologics Inc.: lead

Study Sites (30)

AIDS Health Care Foundation - Research

Beverly Hills, California, 90211, United States

Location

Living Hope Clinical Foundation

Long Beach, California, 90813, United States

Location

Kaiser Permanente Medical Center

Los Angeles, California, 90027, United States

Location

Quest Clinical Research

San Francisco, California, 94115, United States

Location

Kaiser Permanente Medical Center Research Unit

San Francisco, California, 94118, United States

Location

Kaiser Permanente of Colorado

Denver, Colorado, 80205, United States

Location

National Jewish Medical & Research Center

Denver, Colorado, 80206, United States

Location

Whitman-Walker Clinic

Washington D.C., District of Columbia, 20009, United States

Location

South Florida Clinical Research

Atlantis, Florida, 33462, United States

Location

University of Miami, Miller School of Medicine

Miami, Florida, 33136, United States

Location

Orlando Immunology Center

Orlando, Florida, 32802, United States

Location

Associates in Infectious Diseases

Port Saint Lucie, Florida, 34952, United States

Location

Treasure Coast Infectious Disease Consultants

Vero Beach, Florida, 32960, United States

Location

Triple O Medical Services, Inc.

West Palm Beach, Florida, 33401, United States

Location

Northstar Medical Center

Chicago, Illinois, 60657, United States

Location

Indiana University School of Medicine - Wishard Memorial Hospital

Indianapolis, Indiana, 46202, United States

Location

St. Michael's Medical Center

Newark, New Jersey, 07102, United States

Location

AIDS Community Research Initiative of America

New York, New York, 10018, United States

Location

The Brody School of Medicine at ECU

Greenville, North Carolina, 27834, United States

Location

The Research & Educational Group

Portland, Oregon, 97210, United States

Location

Central Texas Clinical Research

Austin, Texas, 78705, United States

Location

North Texas Infectious Disease Consultants

Dallas, Texas, 75246, United States

Location

Valley AIDS Council

Harlingen, Texas, 78550, United States

Location

Therapeutic Concepts

Houston, Texas, 77004, United States

Location

University of Texas Health Science Center

Houston, Texas, 77030, United States

Location

Nationsmed Clinical Research

Houston, Texas, 77036, United States

Location

Dr. Gordon E. Crofoot, MD, PA

Houston, Texas, 77098, United States

Location

Research Access Network

Houston, Texas, 77098, United States

Location

Clinical Research Puerto Rico

San Juan, 00909, Puerto Rico

Location

HOPE Clinical Research

San Juan, 00909, Puerto Rico

Location

MeSH Terms

Interventions

ibalizumab

Limitations and Caveats

ACTG Adherence Questionnaire data were incomplete due to insufficient data collection methods. No clinically meaningful information was gained upon review of these results.

Results Point of Contact

• Title: Stanley T. Lewis, Jr., MD
• Organization: TaiMed Biologics, Inc.

stlewis@taimedbiologics.com

949-769-6543

Study Officials

• Stanley T. Lewis, MD

  TaiMed Biologics Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2008
• First Posted: November 3, 2008
• Study Start: August 1, 2008
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: May 5, 2014
• Results First Posted: April 17, 2014

Record last verified: 2014-04

Locations

PR (2); US (28)