Study of Once Daily Elvucitabine Versus Lamivudine in Participants With a Documented M184V Mutation (Resistance)

A 14 Day Randomized, Double-blind, Study of Once Daily Elvucitabine Versus Lamivudine in Participants With a Documented M184V Mutation

Human immunodeficiency virus (HIV)-1 infected participants receiving long-term therapy with lamivudine or emtricitabine (nucleoside reverse transcriptase inhibitors [NRTIs]) are at risk for the development of a mutation at position M184 on the HIV reverse transcriptase gene. This mutation confers resistance to both drugs (>100 fold increase in the concentration of drug producing 50% inhibition [IC50]).

In-vitro studies with elvucitabine have shown that HIV-1 isolates with the M184V mutation show only a 10-fold increase in IC50 as compared to wild type HIV-1. Alexion Pharmaceuticals Inc. intention is to demonstrate that 10 milligrams (mg) of elvucitabine, administered once per day for 14 days with continued background anti-HIV-1 medications, will demonstrate a fall in HIV-1 ribonucleic acid (RNA) plasma levels, as compared to baseline. The data from this study will guide dosing in future long-term studies in HIV-1 infected participants with the M184V mutation.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Lamivudine; Drug: Elvucitabine

Detailed Description

This was a Phase 2a, 14-Day randomized, double-blind, comparative viral kinetic study of10 mg elvucitabine as compared to lamivudine that was administered once daily (QD) to HIV-1 infected participants with a documented M184V variant. This study also demonstrated the antiviral activity as well as the assessment of safety of the elvucitabine therapy

Participants must be receiving a stable antiretroviral regimen (defined as no change in antiretroviral therapy for at least 4 weeks prior to randomization) that includes lamivudine or emtricitabine. At 72 hours prior to randomization, only lamivudine or emtricitabine will be stopped for washout; participants will continue to receive the other drugs in their prescribed regimen (background antiretroviral therapy) during the 72-hour washout period. Participants will then be randomized to receive blinded elvucitabine or lamivudine in a 1:1 ratio and continue to receive their prescribed background antiretroviral therapy for 14 days on an outpatient basis. Participants will be followed for an additional 14 days post-treatment for safety unless they enroll in the ACH443-018 extension study where they will continue to be treated and followed for safety.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Clinical Trial Site
  • California
    • Sacramento, California, United States, 95817
      • Clinical Trial Site
  • Florida
    • Miami, Florida, United States, 33136
      • Clinical Trial Site
    • Orlando, Florida, United States, 32803
      • Clinical Trial Site
    • West Palm Beach, Florida, United States, 33401
      • Clinical Trial Site
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Clinical Trial Site
  • New York
    • New York, New York, United States, 10003
      • Clinical Trial Site
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Clinically stable HIV-1 infected participants
• Ages >18 and <65 years
• Documented M184V mutation
• CD4 cell count >100 cells/mL
• Plasma HIV-1 RNA levels >5000 and <150,000 copies/milliliter (mL)
• Currently receiving lamivudine or emtricitabine
• Other hematologic and metabolic parameters must be met.
• Provide written informed consent
• Other inclusion criteria apply.

Exclusion Criteria:

• Hepatitis B antigen positive
• HIV-1 genotype positive for more than or equal to 4 protease mutations
• HIV-1 genotype positive for more than or equal to 2 non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations
• Previous therapy with cytotoxic or myelosuppressive drugs in the past 3 months
• Evidence or history of cirrhosis
• Women who are pregnant or breast feeding
• Other exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: B	Drug: Lamivudine; Lamivudine 300 mg QD for 14 days
Experimental: A	Drug: Elvucitabine; Elvucitabine 10 mg QD for 14days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Reduction In Viral Load	14 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with a Treatment Adverse Event	14 days

Collaborators and Investigators

• Sponsor: Alexion
• Collaborators: Achillion, a wholly owned subsidiary of Alexion
• Investigators: Principal Investigator: Judith Feinberg, MD, University of Cincinnati College of Pharmacy, Cincinnati, OH; Principal Investigator: Donna Mildvan, MD, Beth Israel Medical Center, Infectious Diseases, Baird Hall, NY, NY; Principal Investigator: Richard Pollard, MD, UC Davis Medical Center, Div. of Infectious Diseases, Sacramento, CA; Principal Investigator: Michael Saag, MD, UAB Medical Center, AIDS Outpatient Clinic, Birmingham, AL; Principal Investigator: Dushyantha Jayaweera, MD, University of Miami School of Medicine, Infectious Disease Research Unit, Miami, FL; Principal Investigator: Edwin DeJesus, MD, Orlando Immunology Center; Principal Investigator: Melanie Thompson, MD, ACRA Atlanta Georgia

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2006
• Primary Completion (Actual): October 31, 2007
• Study Completion (Actual): October 31, 2007

Study Registration Dates

• First Submitted: April 5, 2006
• First Submitted That Met QC Criteria: April 6, 2006
• First Posted (Estimated): April 7, 2006

Study Record Updates

• Last Update Posted (Actual): August 25, 2023
• Last Update Submitted That Met QC Criteria: August 22, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: HIV-1; treatment experienced
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Lamivudine; Dexelvucitabine
• Other Study ID Numbers: ACH443-014A

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No