A Study to Assess the Long-term Efficacy (24 Weeks) of MPC-4326 in Combination With a 2-3 Drug OBR Relative to the Efficacy of a 3-4 Drug ARV Regimen in Treatment Experienced HIV-1 Infected Subjects Who Are Failing Current Antiretroviral Therapy

NCT01026727 | Terminated Phase 2 DMC

• 1 other identifier: MPC-4326-003.01
• Study Type: interventional
• Target: 2
• Locations: 2 countries
• Sites: 25

Brief Summary

This phase 2b study is designed to assess the long-term efficacy (24 weeks) of MPC-4326 in combination with a 2-3 drug optimized background regimen (OBR) relative to the efficacy of a 3-4 antiretroviral (ARV) regimen in treatment experienced, HIV-1 infected subjects.

Conditions

HIV Infections

Keywords

HIV Infections; Acquired Immunodeficiency Syndrome; Virus Diseases; Sexually Transmitted Diseases, Viral; RNA Virus Infections; Slow Virus Diseases; Immune System Diseases; Sexually Transmitted Diseases; Lentivirus Infections; Infection; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV; treatment experienced; bevirimat

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects with a viral load <50 copies/mL at 24 weeks in each treatment group

  24-weeks

Secondary Outcomes (1)

• The key secondary endpoint is to compare the Viral Load Decrease at 24 weeks in the two treatment arms. VLD is defined as the change from baseline log10 viral load.

  24 weeks

Study Arms (2)

MPC-4326 plus a 2-3 drug optimized background regimen (OBR)

EXPERIMENTAL

MPC-4326 300 mg or 400mg BID plus a 2-3 drug optimized background regimen (OBR)for 24 weeks.

Drug: MPC-4326 plus a 2-3 drug optimized background regimen (OBR)

3-4 drug antiretroviral drugs

ACTIVE COMPARATOR

3-4 commercially available antiretroviral (ARV)drugs for 24 weeks.

Drug: 3-4 commercially available antiretroviral drugs

Interventions

MPC-4326 plus a 2-3 drug optimized background regimen (OBR) DRUG

For treatment arm #1: the MPC-4326 dose will be selected based on the inclusion of raltegravir (i.e., will be limited to 300 mg BID) or inclusion of darunavir (i.e., will be assigned 400 mg BID) in the OBR. If both raltegravir and darunavir are included in the OBR for a subject, the subject will be limited to 300 mg BID

MPC-4326 plus a 2-3 drug optimized background regimen (OBR)

3-4 commercially available antiretroviral drugs DRUG

For treatment arm #2: the antiretroviral regimen, dosage and frequency will be selected by the investigator.

3-4 drug antiretroviral drugs

Eligibility Criteria

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

You may qualify if:

• Voluntarily consent to participate in the study (sign Informed Consent Form), and able to understand study procedures and complete the study.
• Be at least 18 years of age at the time of screening.
• Have a screening plasma HIV-1 RNA value ≥ 1,000 copies/mL
• Be receiving an ARV regimen containing at least 3 drugs which has been unchanged for at least 8 weeks prior to initial screening.
• Have at least two fully active ARVs (exclusive of MPC-4326) as determined by a 'maximal response' on the vircoTYPE assay; R5 tropism testing (if applicable); and treatment history (e.g., naïve to enfuvirtide or integrase inhibitors) that can be combined in a regimen containing a maximum of four ARVs for the 3-4d ARV regimen or three ARVs for the 2-3-drug OBR to be combined with MPC-4326.
• Two NRTIs are not allowed as the only fully-active antiretroviral agents in the 3-4-drug ARV regimen or in the 2-3-drug OBR
• Must have wild type Gag at position 370 (i.e., no polymorphisms at 370)
• Have resistance to at least one agent in each of the three 'classic' ARV drug classes (NRTI, NNRTI, PI) to include documented evidence of resistance on prior resistance tests.
• Females of childbearing potential must agree to the use two forms of contraception from the time of screening until 90 days after completion of dosing.Surfactant-type spermicide gels and contraceptive foam are not recommended, as they increase the rate of HIV transmission.

You may not qualify if:

• Be pregnant or breast feeding
• Presence of any significant acute illness (as determined by the investigator) within 14 days of study entry.
• Presence of any AIDS-related opportunistic infection (Category C according to the CDC Classification System for HIV-1 Infection, 1993 Revised Version) that is unstable in the Investigator's opinion or diagnosed in the 30 days prior to study entry (i.e., Run in Period Day 1).
• A history of cerebrovascular accident or transient ischemic attacks.
• Subjects with the following laboratory parameters within 14 days prior to first dose of study drug:
• Hemoglobin \< 10 g/dL for men and \< 9 g/dL for women
• Absolute neutrophil count \< 1000/mm3
• Platelet count \< 50,000/mm3
• AST or ALT \> 5 times the upper limit of normal inclusive of subjects with a positive HBV surface antigen or HCV antibody test at screening
• Calculated creatinine clearance (ClCr) \<40 mL/min as determined by the Cockcroft-Gault equation
• Subjects who have received radiation therapy or cytotoxic chemotherapeutic agents within 4 weeks prior to the first dose of study drug.
• Subjects who have received treatment with immunomodulating agents such as IL-2, α IFN, β IFN or γ IFN within 4 weeks prior to the first dose of study drug.
• Subjects who use or require a prohibited therapy within 30 days prior to or while participating in this study.
• Receipt of an investigational drug or product, or participation in a drug study within a period of 30 days prior to receiving study medication. For investigational drugs with an elimination half life greater than 10 days, this period will be extended to 60 days and for antibody-based products (i.e., CD4 antibody products, etc.) this period will be extended to 3 months.

Sponsors & Collaborators

• Myrexis Inc.: lead

Study Sites (25)

AIDS Healthcare Foundation Research Center

Beverly Hills, California, 90211, United States

Location

Peter Wolfe, MD, PC

Los Angeles, California, 90036, United States

Location

Quest Clinical Research

San Francisco, California, 94115, United States

Location

Whitman Walker Clinic

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

Location

Therafirst Medical Center

Fort Lauderdale, Florida, 33308, United States

Location

Gary J. Richmond, MD, PA

Fort Lauderdale, Florida, 33316, United States

Location

Wohlfeiler, Piperato and Associates, LLC

Miami Beach, Florida, 33139, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803-1851, United States

Location

AIDS Research Consortium of Atlanta

Atlanta, Georgia, 30308, United States

Location

Community Research Initiative of New England

Boston, Massachusetts, 2215, United States

Location

University of Rochester , Strong Memorial Hospital

Rochester, New York, 14642, United States

Location

North Bronx Health Care Network

The Bronx, New York, 10461, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Kaiser Permanente Immune Deficiency Clinic

Portland, Oregon, 97227, United States

Location

Central Texas Clinical Research

Austin, Texas, 78705, United States

Location

Southwest Infectious Disease

Dallas, Texas, 75204, United States

Location

North Texas Infectious Disease Consultants, PA

Dallas, Texas, 75246, United States

Location

Therapeutic Concepts, P.A

Houston, Texas, 77004, United States

Location

DCOL Center

Longview, Texas, 75605, United States

Location

CARE-ID

Annandale, Virginia, 22003, United States

Location

EHS Pulmonary & Critical Care

Spokane, Washington, 99204, United States

Location

University of British Columbia,Downtown Infectuous Diseases Clinic

Vancouver, British Columbia, V6Z 2C7, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Clinique médicale l'Actuel,

Montreal, Quebec, H2L 4P9, Canada

Location

Clinique Médicale Quartier Latin

Montreal, Quebec, H2L 5B1, Canada

Location

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome; Virus Diseases; Sexually Transmitted Diseases, Viral; RNA Virus Infections; Slow Virus Diseases; Immune System Diseases; Sexually Transmitted Diseases; Lentivirus Infections; Infections; Retroviridae Infections; Immunologic Deficiency Syndromes

Interventions

bevirimat

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Andrew Beelen, MD

  Myrexis Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: December 2, 2009
• First Posted: December 4, 2009
• Study Start: November 1, 2009
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: June 14, 2010

Record last verified: 2010-06

Locations

US (21); CA (4)