Study to Determine the Antiviral Activity and Safety of Alovudine in Nucleoside-experienced HIV-infected Subjects Experiencing Virologic Failure

Randomised, Double Blind, Placebo-controlled Dose Ranging Trial to Determine the Antiviral Activity and Safety of Alovudine in Nucleoside-experienced HIV-infected Subjects Experiencing Virologic Failure

The primary objective was to determine the mean change in HIV viral load from baseline to Week 4 compared with placebo after 4 weeks of treatment in highly experienced HIV-infected patients.

Secondary objectives were to determine (1) the tolerability, hematologic and hepatic safety of different doses of alovudine and (2) the effect of baseline nucleoside genotypic susceptibility on virologic response after 4 weeks of alovudine administration

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Placebo; Drug: Alovudine - low; Drug: Alovudine - medium; Drug: Alovudine - high

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent before any trial procedure
• HIV-1 infected males or females ≥18 years of age
• Screening genotypic resistance report indicating two or more of the following nucleoside reverse transcriptase inhibitors (NRTI) resistance mutations: 41, 67, 70, 210 and 215
• Stable NRTI regimen without stavudine and zidovudine for at least 6 weeks before screening and stable antiretroviral (ARV) background treatment for 3 months before screening
• HIV-1 viral load ≥1000 copies/mL and <75,000 copies/mL at screening
• Change in viral load between previous test within 3 months before screening, using local laboratory for routine tests, and screening test was <1.0 log10 copies/mL
• Acceptable medical history, as assessed by the investigator
• Current stable ARV medication regimen between screening (Visit 1) and Visit 2

Exclusion Criteria:

• ARV medication naïve
• Patients on recent drug holiday, defined as off ARV medications for at least 7 consecutive days within the previous 3 months

• Female patients of child-bearing potential who :

  • have a positive serum pregnancy test
  • are breast feeding,
  • are planning to become pregnant, or
  • are not willing to use a barrier method of contraception
• Prior alovudine use
• Use of investigational medications within 30 days before study entry or during the trial
• Use of immunomodulatory drugs within 3 months before study entry or during the trial (e.g. interferon, cyclosporine, hydroxyurea, interleukin-2)
• Current use of rifampin, rifabutine, isoniazid, pyrazinamide, stavudine, zidovudine, ganciclovir, chronic use of hepatotoxic drugs, anti-tumour therapy or probenecid

• Laboratory values:

  • Neutrophils of Grade 2 or greater abnormality
  • Hemoglobin of Grade 2 or greater abnormality
  • Platelets: Grade 2 or greater abnormality
  • Creatinine of ≥1.25 Upper limit of the normal (ULN)
  • Lipase of Grade 1 or greater abnormality
  • Alanine aminotransaminase (ALT) or Aspartate aminotransaminase (AST) of Grade 2 or greater abnormality
  • Direct bilirubin of Grade 1 or greater abnormality
• CD4 ≤50 cells/mm3
• Hepatitis B (+HBsAg or +HBcAB) or C +Hepatitis C virus (+HCV AB ) co-infection, chronic hepatitis, on-going hepatitis or pancreatitis
• Any new or active AIDS-defining event within 30 days before study entry
• Inability to adhere to the requirements of the protocol, including active substance abuse as assessed by the investigator
• In the opinion of the investigator, likely survival of less than 6 months because of underlying disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: Alovudine - low	Drug: Placebo; Drug: Alovudine - low
Experimental: Alovudine - medium	Drug: Placebo; Drug: Alovudine - medium
Experimental: Alovudine - high	Drug: Alovudine - high

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean change in HIV viral load measured from plasma samples	Up to 4 weeks after drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of virologic responders per treatment arm		Up to 4 weeks after drug administration
Proportion of patients experiencing a change of viral load	viral load of ≥1 log10 from baseline to Week 4	Up to 4 weeks after drug administration
Mean change in CD4+ cell count		Up to 4 weeks after drug administration
Percentage of 0.5 virologic responders per treatment arm		Up to 4 weeks after drug administration
Percentage of load responders per treatment arm		Up to 4 weeks after drug administration
Percentage of 0.7 to 0.9 virologic responders per treatment arm		Up to 4 weeks after drug administration
Number of patients with adverse events		Up to 4 weeks after drug administration
Number of patients with laboratory test abnormalities and with respect to Division of AIDS (DAIDS) grading		Up to 4 weeks after drug administration
Number of patients with serious adverse events		Up to 4 weeks after drug administration
Number of patients who discontinued due to adverse event		Up to 4 weeks after drug administration
Mean change in CD8+ cell count		Up to 4 weeks after drug administration
Number of patients with abnormal changes in laboratory parameters		Up to 4 weeks after drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): December 1, 2004

Study Registration Dates

• First Submitted: September 4, 2014
• First Submitted That Met QC Criteria: September 4, 2014
• First Posted (Estimate): September 5, 2014

Study Record Updates

• Last Update Posted (Estimate): September 5, 2014
• Last Update Submitted That Met QC Criteria: September 4, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• 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; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites; Alovudine; Dideoxynucleosides
• Other Study ID Numbers: 1211.1