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

Boehringer Ingelheim

Status and phase: Completed; Phase 2

Conditions: HIV Infections

Treatments: Drug: Alovudine - medium; Drug: Alovudine - low; Drug: Alovudine - high; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02232581

1211.1

Details and patient eligibility

About

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

Enrollment: 72 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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72 participants in 4 patient groups, including a placebo group

Alovudine - low

Experimental group

Treatment:

Drug: Alovudine - low

Drug: Placebo

Alovudine - medium

Experimental group

Treatment:

Drug: Alovudine - medium

Drug: Placebo

Alovudine - high

Experimental group

Treatment:

Drug: Alovudine - high

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo