Clinical trial NCT01026727: 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
Official title: A Phase 2b Multicenter, Randomized, Open Label, Comparative Trial of MPC-4326 in Combination With a Two to Three Drug Optimized Background Regimen Versus an Optimized, Three to Four Drug Antiretroviral Regimen for the Treatment of Triple Class Antiretroviral Experienced, HIV-1 Infected Subjects Failing Current Therapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
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
Lead sponsor: Myrexis Inc.
Sponsor class: INDUSTRY
First posted: 2009-12-04
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Proportion of subjects with a viral load <50 copies/mL at 24 weeks in each treatment group
timeFrame: 24-weeks
Secondary outcomes:
measure: 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.
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: AIDS Healthcare Foundation Research Center
state: California
city: Los Angeles
country: United States
facility: Peter Wolfe, MD, PC
state: California
city: San Francisco
country: United States
facility: Quest Clinical Research
state: California
city: Washington
country: United States
facility: Whitman Walker Clinic
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Therafirst Medical Center
state: Florida
city: Fort Lauderdale
country: United States
facility: Gary J. Richmond, MD, PA
state: Florida
city: Miami Beach
country: United States
facility: Wohlfeiler, Piperato and Associates, LLC
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Boston
country: United States
facility: Community Research Initiative of New England
state: Massachusetts
city: Bronx
country: United States
facility: North Bronx Health Care Network
state: New York
city: Rochester
country: United States
facility: University of Rochester , Strong Memorial Hospital
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Portland
country: United States
facility: Kaiser Permanente Immune Deficiency Clinic
state: Oregon
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Dallas
country: United States
facility: Southwest Infectious Disease
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Disease Consultants, PA
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, P.A
state: Texas
city: Longview
country: United States
facility: DCOL Center
state: Texas
city: Annandale
country: United States
facility: CARE-ID
state: Virginia
city: Spokane
country: United States
facility: EHS Pulmonary & Critical Care
state: Washington
city: Vancouver
country: Canada
facility: University of British Columbia,Downtown Infectuous Diseases Clinic
state: British Columbia
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Clinique médicale l'Actuel,
state: Quebec
city: Montreal
country: Canada
facility: Clinique Médicale Quartier Latin
state: Quebec
Study officials:
affiliation: Myrexis Inc.
name: Andrew Beelen, MD
role: STUDY_DIRECTOR
References: