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

NCT ID: NCT01026727

Last Updated: 2010-06-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2010-06-30

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.

Detailed Description

Standard antiretroviral therapies for the treatment of HIV/AIDS, while effective for varying lengths of time, can be rendered inadequate for viral suppression by the emergence of drug resistant virus, which can include resistance to entire mechanistic classes of drugs. Thus, there exists a significant unmet medical need for new highly potent antiretroviral agents with novel mechanisms of action. The novel mechanism of action of MPC-4326 suggests that MPC-4326 may have utility for the treatment of HIV-1 infected patients failing current regimens due to the development of drug resistance.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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

Group Type: EXPERIMENTAL

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

Intervention Type: 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

3-4 drug antiretroviral drugs

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

Group Type: ACTIVE_COMPARATOR

3-4 commercially available antiretroviral drugs

Intervention Type: DRUG

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

Interventions

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

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

Intervention Type: DRUG

3-4 commercially available antiretroviral drugs

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Voluntarily consent to participate in the study (sign Informed Consent Form), and able to understand study procedures and complete the study.

2. Be at least 18 years of age at the time of screening.

3. Have a screening plasma HIV-1 RNA value ≥ 1,000 copies/mL

4. Be receiving an ARV regimen containing at least 3 drugs which has been unchanged for at least 8 weeks prior to initial screening.

5. 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.

6. 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

7. Must have wild type Gag at position 370 (i.e., no polymorphisms at 370)

8. 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.

9. 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.

Exclusion Criteria

1. Be pregnant or breast feeding

2. Presence of any significant acute illness (as determined by the investigator) within 14 days of study entry.

3. 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).

4. A history of cerebrovascular accident or transient ischemic attacks.

5. Subjects with the following laboratory parameters within 14 days prior to first dose of study drug:

1. Hemoglobin < 10 g/dL for men and < 9 g/dL for women

2. Absolute neutrophil count < 1000/mm3

3. Platelet count < 50,000/mm3

4. 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

5. Calculated creatinine clearance (ClCr) <40 mL/min as determined by the Cockcroft-Gault equation

6. Subjects who have received radiation therapy or cytotoxic chemotherapeutic agents within 4 weeks prior to the first dose of study drug.

7. 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.

8. Subjects who use or require a prohibited therapy within 30 days prior to or while participating in this study.

9. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Myrexis Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Myriad Pharmaceuticals, Inc

Principal Investigators

Andrew Beelen, MD

Role: STUDY_DIRECTOR

Myrexis Inc.

Locations

AIDS Healthcare Foundation Research Center

Beverly Hills, California, United States

Peter Wolfe, MD, PC

Los Angeles, California, United States

Quest Clinical Research

San Francisco, California, United States

Whitman Walker Clinic

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

Therafirst Medical Center

Fort Lauderdale, Florida, United States

Gary J. Richmond, MD, PA

Fort Lauderdale, Florida, United States

Wohlfeiler, Piperato and Associates, LLC

Miami Beach, Florida, United States

Orlando Immunology Center

Orlando, Florida, United States

AIDS Research Consortium of Atlanta

Atlanta, Georgia, United States

Community Research Initiative of New England

Boston, Massachusetts, United States

University of Rochester , Strong Memorial Hospital

Rochester, New York, United States

North Bronx Health Care Network

The Bronx, New York, United States

Duke University

Durham, North Carolina, United States

Kaiser Permanente Immune Deficiency Clinic

Portland, Oregon, United States

Central Texas Clinical Research

Austin, Texas, United States

Southwest Infectious Disease

Dallas, Texas, United States

North Texas Infectious Disease Consultants, PA

Dallas, Texas, United States

Therapeutic Concepts, P.A

Houston, Texas, United States

DCOL Center

Longview, Texas, United States

CARE-ID

Annandale, Virginia, United States

EHS Pulmonary & Critical Care

Spokane, Washington, United States

University of British Columbia,Downtown Infectuous Diseases Clinic

Vancouver, British Columbia, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Clinique médicale l'Actuel,

Montreal, Quebec, Canada

Clinique Médicale Quartier Latin

Montreal, Quebec, Canada

Countries

United States; Canada

Other Identifiers

MPC-4326-003.01

Identifier Type: -

Identifier Source: org_study_id