Efficacy and Safety of Raltegravir (RAL) in Treatment-experienced HIV-1 Infected Adult Chinese Patients

An Open Pilot Study to Evaluate the Efficacy and Safety, Tolerability of Raltegravir（RAL）in Treatment-experienced HIV-1 Infected Adult Chinese Patients

To assess the safety, tolerability and efficacy of Raltegravir (RAL) when combined with other antiretroviral drugs in treatment-experienced Chinese HIV-infected patients, including those with multi-drug resistant HIV-1 infection or drug intolerance.

Study Overview

• Status: Unknown
• Conditions: HIV
• Intervention / Treatment: Drug: raltegravir

Detailed Description

An open, prospective, uncontrolled pilot study to evaluate the efficacy and safety of raltegravir in treatment-experienced HIV-1 infected adult patients who have failed the previous antiretroviral treatment due to drug resistance or drug intolerance.

1. Patients Enrollment:

   HIV-infected patients aged over 18 who have failed previous antiretroviral treatment with multi-drug resistant or with multi-drug intolerance are eligible. And at least 50 subjects are to be concluded in the trial.

   ⅰ) The diagnostic criteria of HIV/AIDS refer to guidelines for diagnosis and treatment of HIV/AIDS in China(2005).

   ⅱ) Treatment failure will be defined as follows: (i): HIV viral load has decreased by less than 1 log copies/ml in patients with 8 weeks of HAART, or (ii) HIV viral load is still detectable after 6 months of HAART;or (iii) reappearance of a detectable viral load after HAART has led to undetectable viral load.

   ⅲ) The definition of drug resistance is based on a genotypic resistance test.

   ⅳ) Drug intolerance involves all the serious antiretroviral drug related adverse events, such as AZT related bone marrow suppression, NVP or EFV related serious liver damage and allergic reaction, d4T related lactic acidosis, pancreatitis and peripheral neuritis, etc.

2. Patients enrolled in the study sign consent form.

3. Antiretroviral regimen for the subjects:

   The patients enrolled in the study accept a treatment regimen of RAL 400 mg twice daily plus OBT (optimized background therapy), which is selected on the basis of the patient's antiretroviral treatment history, results from all available genotypic resistance tests, previous or current laboratory abnormalities and intolerance to other antiretroviral drugs, and shall, if possible, contain two anti-retroviral drugs fully active against the patient's virus by genotype.

4. Data collection:

   For each patient, detection of HIV viral load and CD4+ T lymphocyte count is done at screening, and at weeks 4, 12, 24 and 48. The safety profile of RAL is monitored according to patients' complaints and the results of physical and laboratory examinations. Plasma HIV RNA viral loads are determined by HIV-1 Quantiplex(bDNA) assay approved by FDA. CD4+ T lymphocytes are counted with flow cytometry. Any drug-related adverse events that patients experience during treatment will be recorded, such as nausea, vomiting, abdominal pain, abodominal distension, diarrhea, fever, headache, dizzy, fatigue etc. Laboratory examinations cover blood, urine and stool routine, liver and renal function, electrolytes, blood glucose, blood lipid, electrocardiogram etc.

5. Endpoints of study:

The primary endpoint is the the safety and tolerability of RAL 400 mg b.i.d. in combination with OBT, assessed by review of the accumulated safety data in HIV-infected adult patients. The secondary endpoint is antiretroviral activity of RAL 400 mg b.i.d. in combination with OBT as measured by change at week 24 in viral load from baseline, increase of CD4+ T lymphocytes compared to baseline and proportions of patients with: viral load less than 400 copies/ml; viral load less than 50 copies/ml; and a reduction in viral load from baseline exceeding 1.0 log10 copies/ml.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201508
      • Shanghai Public Health Clinical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• HIV-infected patients aged over 18 who have failed previous antiretroviral treatment with multi-drug resistant or with multi-drug intolerance

Exclusion Criteria:

• The patient is aged below 18 or over 65 years
• The patient has serious opportunistic infections or tumors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: raltegravir; HIV-infected patients aged over 18 who have failed previous antiretroviral treatment with multi-drug resistant or with multi-drug intolerance are to accept Ral plus OBT.	Drug: raltegravir; RAL 400 mg twice daily plus OBT (optimized background therapy) for 48 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the safety and tolerability of RAL 400 mg b.i.d. in combination with optimized background therapy (OBT), assessed by review of the accumulated safety data in HIV-infected adult patients.	48 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
antiretroviral activity of RAL 400 mg b.i.d. in combination with OBT as measured by change at week 24 in viral load from baseline, increase of CD4+ T lymphocytes compared to baseline	48 weeks

Collaborators and Investigators

• Sponsor: Shanghai Public Health Clinical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Anticipated): May 1, 2012
• Study Completion (Anticipated): October 1, 2012

Study Registration Dates

• First Submitted: September 13, 2010
• First Submitted That Met QC Criteria: September 13, 2010
• First Posted (Estimate): September 14, 2010

Study Record Updates

• Last Update Posted (Estimate): September 14, 2010
• Last Update Submitted That Met QC Criteria: September 13, 2010
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Keywords: HIV-1; raltegravir; drug resistance
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Raltegravir Potassium
• Other Study ID Numbers: RAL-001

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