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

HIV Clinical Trial

— TMB-202  

Official title:

A Phase 2b, Randomized, Double-Blinded, 48-Week, Multicenter, Dose-Response Study of Ibalizumab Plus an Optimized Background Regimen in Treatment-Experienced Patients Infected With HIV-1(Amended to 24-Weeks)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00784147
• Other study ID #: TMB-202 Amendment 2
• Status: Completed
• Phase: Phase 2
• First received: October 30, 2008
• Last updated: April 17, 2014
• Start date: August 2008
• Est. completion date: April 2011

Study information

• Verified date: April 2014
• Source: TaiMed Biologics Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 113
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• Ibalizumab
Ibalizumab 800 mg IV every 2 weeks
• Ibalizumab
Ibalizumab 2000 mg IV every 4 weeks

Locations

Country	Name	City	State
Puerto Rico	Clinical Research Puerto Rico	San Juan
Puerto Rico	HOPE Clinical Research	San Juan
United States	South Florida Clinical Research	Atlantis	Florida
United States	Central Texas Clinical Research	Austin	Texas
United States	AIDS Health Care Foundation - Research	Beverly Hills	California
United States	Northstar Medical Center	Chicago	Illinois
United States	North Texas Infectious Disease Consultants	Dallas	Texas
United States	Kaiser Permanente of Colorado	Denver	Colorado
United States	National Jewish Medical & Research Center	Denver	Colorado
United States	The Brody School of Medicine at ECU	Greenville	North Carolina
United States	Valley AIDS Council	Harlingen	Texas
United States	Dr. Gordon E. Crofoot, MD, PA	Houston	Texas
United States	Nationsmed Clinical Research	Houston	Texas
United States	Research Access Network	Houston	Texas
United States	Therapeutic Concepts	Houston	Texas
United States	University of Texas Health Science Center	Houston	Texas
United States	Indiana University School of Medicine - Wishard Memorial Hospital	Indianapolis	Indiana
United States	Living Hope Clinical Foundation	Long Beach	California
United States	Kaiser Permanente Medical Center	Los Angeles	California
United States	University of Miami, Miller School of Medicine	Miami	Florida
United States	AIDS Community Research Initiative of America	New York	New York
United States	St. Michael's Medical Center	Newark	New Jersey
United States	Orlando Immunology Center	Orlando	Florida
United States	Associates in Infectious Diseases	Port St. Lucie	Florida
United States	The Research & Educational Group	Portland	Oregon
United States	Kaiser Permanente Medical Center Research Unit	San Francisco	California
United States	Quest Clinical Research	San Francisco	California
United States	Treasure Coast Infectious Disease Consultants	Vero Beach	Florida
United States	Whitman-Walker Clinic	Washington	District of Columbia
United States	Triple O Medical Services, Inc.	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
TaiMed Biologics Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportion of Patients With Viral Load <200 Copies/mL at Week 24	This measure was assessed in the same manner as the primary efficacy analysis for the proportion of patients achieving HIV-1 RNA levels below 200 copies/mL at Week 24 of the study.	Week 24	No
Other	Proportion of Patients With Viral Load <400 Copies/mL at Week 24	This efficacy measure was assessed in the same manner as the primary efficacy analysis to determine the proportion of the total population achieving HIV-1 RNA levels <400 copies at Week 24 of the study.	Week 24	No
Other	Proportion of Patients With a 1.0 log10 or Greater Reduction in Viral Load at Week 24	This efficacy assessment was performed in the same manner as the primary efficacy analysis for the proportion of the total population achieving at least a 1.0 log10 reduction from Baseline in HIV-1 RNA.	Week 24	No
Other	Proportion of Patients With a 0.5 log10 or Greater Reduction in Viral Load at Week 24	This efficacy assessment was performed in the same manner as the primary efficacy analysis for the proportion of the total population achieving at least a 0.5 log10 reduction from the Baseline measurement in HIV-1 RNA at Week 24 of the study.	Week 24	No
Primary	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	No
Secondary	Mean Change From Baseline in Viral Load (log10) at Week 24/EOS	The mean change in HIV-1 RNA (log10) from the Baseline measurement was analyzed at Week 24/End of Study using a generalized linear model at each scheduled study visit.	Week 24 / End of Study	No
Secondary	Mean Change From Baseline in CD4+ T-Cell Count at Week 24/EOS	The mean change in CD4+ T-cell count from the Baseline measurement at Week 24/End of Study was summarized at each scheduled time point by treatment group.	Week 24 / End of Study	No