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

NCT ID: NCT00784147

Last Updated: 2014-05-05

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

113 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-08-31

Study Completion Date

2011-04-30

Brief Summary

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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).

Detailed Description

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The primary objectives of this study are to:

* Evaluate the dose-response relationship of antiviral activity of the ibalizumab dose regimens at Week 24 in order to determine the optimal dose and regimen. The primary evaluation of effectiveness will be based on the proportion of patients achieving undetectable viral loads at Week 24.
* Evaluate the safety and tolerability of two dose regimens of ibalizumab for dose selection

The secondary objectives of this study are to:

* Evaluate changes from Baseline in viral load, CD4+ cell counts, and time to loss of virologic response (TLOVR)
* Characterize HIV-1 sensitivity/susceptibility changes associated with ibalizumab administration in combination with OBR
* Determine the presence and significance of anti-ibalizumab antibodies, if any (immunogenicity of ibalizumab)
* Assess CD4 receptor density and occupancy
* Determine the impact of ibalizumab on quality of life as assessed by patient-reported outcomes on questionnaires
* Evaluate the pharmacokinetic profile of two dose regimens of ibalizumab at steady state

Conditions

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HIV

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Ibalizumab 800 mg

every 2 weeks, combined with an Optimized Background Regimen

Group Type ACTIVE_COMPARATOR

Ibalizumab

Intervention Type DRUG

Ibalizumab 800 mg IV every 2 weeks

Ibalizumab 2000 mg

every 4 weeks, combined with an Optimized Background Regimen

Group Type ACTIVE_COMPARATOR

Ibalizumab

Intervention Type DRUG

Ibalizumab 2000 mg IV every 4 weeks

Interventions

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Ibalizumab

Ibalizumab 800 mg IV every 2 weeks

Intervention Type DRUG

Ibalizumab

Ibalizumab 2000 mg IV every 4 weeks

Intervention Type DRUG

Other Intervention Names

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TNX-355; Hu5A8 TNX-355; Hu5A8

Eligibility Criteria

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Inclusion Criteria

1. Are capable of understanding and have voluntarily signed the informed consent document
2. Have documented HIV-1 infection by official, signed, written history (eg, laboratory report), otherwise an HIV-antibody test will be performed
3. 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
4. Are able and willing to comply with all protocol requirements and procedures
5. Are 18 years of age or older
6. Have a life expectancy that is \>6 months.
7. 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
8. 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
9. 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
10. 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

Exclusion Criteria

1. 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
2. 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
3. Any significant acute illness within 1 week before the initial administration of study drug
4. 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
5. Any immunomodulating therapy (including interferon), systemic steroids, or systemic chemotherapy within 12 weeks before randomization
6. Any investigational therapy within 30 days before randomization, except for HIV-agents available in expanded-access programs
7. Any prior exposure to ibalizumab (formerly TNX-355 and Hu5A8)
8. Any vaccination within 21 days before randomization
9. Any female patient who either is pregnant, intends to become pregnant, or is currently breast-feeding
10. 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
11. Any previous clinically significant allergy or hypersensitivity to any excipient in the ibalizumab formulation
12. Any radiation therapy during the 28 days before first administration of investigational medication
13. 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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TaiMed Biologics Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stanley T. Lewis, MD

Role: STUDY_DIRECTOR

TaiMed Biologics Inc.

Locations

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AIDS Health Care Foundation - Research

Beverly Hills, California, United States

Site Status

Living Hope Clinical Foundation

Long Beach, California, United States

Site Status

Kaiser Permanente Medical Center

Los Angeles, California, United States

Site Status

Quest Clinical Research

San Francisco, California, United States

Site Status

Kaiser Permanente Medical Center Research Unit

San Francisco, California, United States

Site Status

Kaiser Permanente of Colorado

Denver, Colorado, United States

Site Status

National Jewish Medical & Research Center

Denver, Colorado, United States

Site Status

Whitman-Walker Clinic

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

Site Status

South Florida Clinical Research

Atlantis, Florida, United States

Site Status

University of Miami, Miller School of Medicine

Miami, Florida, United States

Site Status

Orlando Immunology Center

Orlando, Florida, United States

Site Status

Associates in Infectious Diseases

Port Saint Lucie, Florida, United States

Site Status

Treasure Coast Infectious Disease Consultants

Vero Beach, Florida, United States

Site Status

Triple O Medical Services, Inc.

West Palm Beach, Florida, United States

Site Status

Northstar Medical Center

Chicago, Illinois, United States

Site Status

Indiana University School of Medicine - Wishard Memorial Hospital

Indianapolis, Indiana, United States

Site Status

St. Michael's Medical Center

Newark, New Jersey, United States

Site Status

AIDS Community Research Initiative of America

New York, New York, United States

Site Status

The Brody School of Medicine at ECU

Greenville, North Carolina, United States

Site Status

The Research & Educational Group

Portland, Oregon, United States

Site Status

Central Texas Clinical Research

Austin, Texas, United States

Site Status

North Texas Infectious Disease Consultants

Dallas, Texas, United States

Site Status

Valley AIDS Council

Harlingen, Texas, United States

Site Status

Therapeutic Concepts

Houston, Texas, United States

Site Status

University of Texas Health Science Center

Houston, Texas, United States

Site Status

Nationsmed Clinical Research

Houston, Texas, United States

Site Status

Dr. Gordon E. Crofoot, MD, PA

Houston, Texas, United States

Site Status

Research Access Network

Houston, Texas, United States

Site Status

Clinical Research Puerto Rico

San Juan, , Puerto Rico

Site Status

HOPE Clinical Research

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

Other Identifiers

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TMB-202 Amendment 2

Identifier Type: -

Identifier Source: org_study_id

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