Elvucitabine/Efavirenz/Tenofovir Versus Lamivudine/Efavirenz/Tenofovir in Human Immunodeficiency Virus (HIV)-1 Infected, Treatment-naive Participants

NCT00350272 | Completed Phase 2 Results DMC

• 1 other identifier: ACH443-015
• Study Type: interventional
• Target: 76
• Locations: 2 countries
• Sites: 26

Brief Summary

Elvucitabine, a novel nucleoside analog, is being studied as a treatment for participants with human immunodeficiency virus (HIV)-1. This Phase 2 study will enroll 60 HIV-1-naive participants to assess the efficacy and safety of elvucitabine compared to lamivudine in combination with tenofovir and efavirenz as measured by changes in the participant's HIV-ribonucleic acid (RNA) level and CD4 cell count. The study treatment will be 12 weeks of blinded study medication followed by an additional 84 weeks of open-label treatment if the participant's response to treatment meets certain endpoints. The pharmacokinetics of elvucitabine will also be assessed during the study.

Conditions

HIV Infections

Keywords

HIV-1 treatment naive

Outcome Measures

Primary Outcomes (2)

• The Proportion Of Participants With Virologic Response For 10 mg/Day Elvucitabine In HIV-1-Infected Participants By 12 Weeks Compared With The Proportion Of Participants With Lamivudine 300 mg/Day

  The proportion of participants having achieved a virologic response for elvucitabine 10 mg/day in combination with efavirenz and tenofovir in HIV-1-infected participants over 12 weeks compared with the proportion of participants having achieved a virologic response for lamivudine 300 mg/day in combination with efavirenz and tenofovir. Virologic response was defined as having achieved undetectable (\<50 copies/mL) HIV-1 RNA levels from baseline assessment.

  12 weeks

• The Safety Profile Of Elvucitabine.

  Determination of the safety profile of elvucitabine as defined by the frequency, type and severity of treatment-emergent adverse events (AEs) and the frequency of Grade 3 and Grade 4 laboratory abnormalities.

  12 weeks

Study Arms (2)

Elvucitabine, Efavirenz, Tenofovir

EXPERIMENTAL

Elvucitabine (blinded) 10 milligrams (mg)/day in combination with open-label efavirenz 600 mg daily and open-label tenofovir 300 mg daily, all administered orally, over 12 weeks. Eligible participants continued with an additional 84 weeks of open-label treatment (through Week 96). Participants who experienced at least a 2 log10 decrease in HIV-1 RNA from Baseline or who had an HIV-1 RNA level of less than 400 copies/ mL at Week 10 and had not experienced any Grade 3 or 4 hematological toxicity as of the Week 10 measurement were considered eligible for an additional 84 weeks of open-label treatment after Week 12.

Drug: Elvucitabine; Drug: Tenofovir; Drug: Efavirenz

Lamivudine, Efavirenz, Tenofovir

ACTIVE COMPARATOR

Lamivudine (blinded) 300 mg daily in combination with open-label efavirenz 600 mg daily and open-label tenofovir 300 mg daily, all administered orally, over 12 weeks. Eligible participants continued with an additional 84 weeks of open-label treatment (through Week 96). Participants who experienced at least a 2 log10 decrease in HIV-1 RNA from Baseline or who had an HIV-1 RNA level of less than 400 copies/mL at Week 10 and had not experienced any Grade 3 or 4 hematological toxicity as of the Week 10 measurement were considered eligible for an additional 84 weeks of open-label treatment after Week 12.

Drug: Lamivudine; Drug: Tenofovir; Drug: Efavirenz

Interventions

Elvucitabine DRUG

Elvucitabine 10 mg orally daily

Also known as: ACH-126,443

Elvucitabine, Efavirenz, Tenofovir

Lamivudine DRUG

Lamivudine 300 mg orally daily

Also known as: 3TC

Lamivudine, Efavirenz, Tenofovir

Tenofovir DRUG

Tenofovir open-label 300 mg orally daily

Also known as: Viread

Elvucitabine, Efavirenz, Tenofovir; Lamivudine, Efavirenz, Tenofovir

Efavirenz DRUG

Efavirenze open-label 600 mg orally daily

Also known as: Sustiva

Elvucitabine, Efavirenz, Tenofovir; Lamivudine, Efavirenz, Tenofovir

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• A participant must meet the following criteria at Screening to be enrolled in this study:
• Are male or female. Sexually active men with partners of childbearing potential must agree to use an acceptable form of contraception as determined by the investigator (for example, oral contraceptives, double-barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or vasectomy) during participation in the study. Female participants cannot be pregnant or lactating/breast-feeding and must be surgically sterile, postmenopausal as defined later, or practicing an effective method of birth control as determined by the investigator (for example oral contraceptives, double-barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or partner with vasectomy). A woman may be considered postmenopausal if she is at least 50 years or older, has a history of no menses for at least 12 months, and has a follicle-stimulating hormone (FSH) level over the upper limit of normal for reproductive aged women.
• Are 18 through 65 years old
• Have documented HIV-1 infection by written prior history and clinically stable with no AIDS-defining events in the 3 months prior to Screening
• Have plasma HIV-1 RNA levels greater than or equal to 5000 copies/mL at Screening
• Are HIV-1 strain sensitive to elvucitabine, lamivudine, or emtricitabine as demonstrated by the absence of the M184V, M184I, and D237E mutations by TRUGENE HIV-1 Genotyping Kit
• Are HIV-1 strain genotypically sensitive to efavirenz (negative for K103 and Y188L mutations) and tenofovir (negative for K65R mutation) by TRUGENE HIV-1 Genotyping Kit
• Have a CD4 count greater than or equal to 200 cells/mL and less than 500 cells/mL
• Have acceptable hematologic and chemistry parameters, including the following:
• Hemoglobin (Hgb) greater than or equal to 11 grams (g)/deciliter (dL)
• Absolute neutrophil count greater than or equal to 2000 cells/mm\^3
• Platelets greater than or equal to 125 000/mm\^3
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 1.5 times the upper limit of normal
• Total bilirubin less than or equal to 1.5 times the upper limit of normal
• Creatinine within normal range

You may not qualify if:

• Participants meeting any of the following criteria at Screening will be excluded from the study:
• Are hepatitis B surface antigen positive, and/or hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive
• Have previous therapy with agents with significant systemic myelosuppressive or cytotoxic potential within the 3 months prior to Screening or the expected need for such therapy during the study
• Have previous use or need for bone marrow colony-stimulating factors such as Epogen, Procrit, or Neupogen
• Have had previous antiretroviral therapy
• Have evidence or history of cirrhosis
• Have recent (within 3 months of Screening) history of alcohol abuse, physical dependence to any opioid, cocaine, lysergic acid diethylamide (LSD) or amphetamines, or history of drug addiction within the last 12 months
• Have inability to tolerate oral medication
• Are pregnant or breast-feeding if female
• Have any clinical condition or prior therapy that, in the investigator's opinion, would make the participant unsuitable for the study or unable to comply with the dosing requirements
• Have received treatment with any other investigational drug within 30 days prior to Screening
• Have current active mental illness or a history of significant mental illness (for example, severe depression, schizophrenia, history of suicidal ideations, or suicide attempts)

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead
• Achillion, a wholly owned subsidiary of Alexion: collaborator

Study Sites (26)

Clinical Trial Site

Little Rock, Arkansas, 72207, United States

Location

Clinical Trial Site

Long Beach, California, 90813, United States

Location

Clinical Trial Site

Los Angeles, California, 90069, United States

Location

Clinical Trial Site

Washington D.C., District of Columbia, 20007, United States

Location

Clinical Trial Site

Clearwater, Florida, 33765, United States

Location

Clinical Trial Site

Fort Myers, Florida, 33901, United States

Location

Clinical Trial Site

Miami, Florida, 33133, United States

Location

Clinical Trial Site

Miami, Florida, 33136, United States

Location

Clinical Trial Site

Orlando, Florida, 32803, United States

Location

Clinical Trial Site

Tampa, Florida, 33602, United States

Location

Clinical Trial Site

Tampa, Florida, 33614, United States

Location

Clinical Trial Site

West Palm Beach, Florida, 33401, United States

Location

Clinical Trial Site

Chicago, Illinois, 60611, United States

Location

Clinical Trial Site

Wichita, Kansas, 67214, United States

Location

Clinical Trial Site

Washington D.C, Maryland, 20007, United States

Location

Clinical Trial Site

Boston, Massachusetts, 02215, United States

Location

Clinical Trial Site

Newark, New Jersey, 07102, United States

Location

Clinical Trial Site

New York, New York, 10003, United States

Location

Clinical Trial Site

Austin, Texas, 75705, United States

Location

Clinical Trial Site

Dallas, Texas, 75204, United States

Location

Clinical Trial Site

Houston, Texas, 77004, United States

Location

Clinical Trial Site

Houston, Texas, 77009, United States

Location

Clinical Trial Site

Houston, Texas, 77030, United States

Location

Clinical Trial Site

Houston, Texas, 77098, United States

Location

Clinical Trial Site

Hampton, Virginia, 23666, United States

Location

Clinical Trial Site

San Juan, 00909, Puerto Rico

Location

MeSH Terms

Conditions

HIV Infections

Interventions

dexelvucitabine; Lamivudine; Tenofovir; efavirenz

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Alexion Pharmaceuticals Inc.
• Organization: Alexion Pharmaceuticals Inc.

clinicaltrials@alexion.com

855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2006
• First Posted: July 10, 2006
• Study Start: May 1, 2006
• Primary Completion: August 1, 2007
• Study Completion: April 1, 2009
• Last Updated: August 30, 2023
• Results First Posted: March 22, 2016

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share

Locations

PR (1); US (25)