Efficacy and Safety of MK-0518 in Treatment-Experienced HIV-1 Infected Adult Patients With Hemophilia

HIV Infection Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety, Tolerability of MK-0518 in Treatment-Experienced HIV-1 Infected Adult Patients With Hemophilia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT00797381
• Other study ID #: CN2009
• Status: Not yet recruiting
• Phase: N/A
• First received: November 24, 2008
• Last updated: November 24, 2008
• Start date: May 2009
• Est. completion date: May 2011

Study information

• Verified date: November 2008
• Source: Shanghai Public Health Clinical Center
• Contact: Hongzhou Lu, PhD
• Phone: 0086-2157248758
• Email: luhongzhou[@]fudan.edu.cn
• Is FDA regulated: No
• Health authority: China: Ethics CommitteeUnited States: Federal Government
• Study type: Observational

Clinical Trial Summary

This is an randomized, double-blind, placebo-controlled study to assess the safety, tolerability and efficacy of MK-0518 compared to placebo when combined with other antiretroviral drugs, in treatment-experienced HIV-infected patients with hemophilia.

Subjects enrolled in the study sign the consent form, then are randomly assigned to MK-0518 400 mg twice daily plus optimized background therapy (OBT) group or placebo plus OBT group.Each group concludes at least 50 subjects. For each patient, detection of HIV viral load and CD4+ T lymphocyte count is done at screening, and at weeks 4, 8, 12 and 24. The safety profile of MK-0518 is monitored according to patients' complaints and the results of physical and laboratory examinations.

The safety and efficacy of MK-0518 400 mg b.i.d. compared to placebo, both in combination with OBT, will be assessed by review of the accumulated study data in HIV-infected patients with hemophilia.

Description:

1. Objective

To assess the safety, tolerability and efficacy of MK-0518 compared to placebo when combined with other antiretroviral drugs, in treatment-experienced HIV-infected patients with hemophilia.

2. Background and Significance

Current anti-HIV drugs are mainly reverse transcriptase inhibitors, which include nucleoside reverse transcriptase inhibitors(NRTIs) and non-nucleoside reverse transcriptase inhibitors(NNRTIs), and protease inhibitors(PIs). However, HIV can become rapidly resistant to them due to its high rate of mutation while replicating, which forces people to seek new targets for anti-HIV therapy continually. Integrase is an another enzyme essential for HIV reproduction. To inhibit integrase activity is an effective measure to suppress HIV replication. MK-0518(Raltegravir）was approved by the United States Food and Drug Administration(FDA) on October 12th 2007 due to its potent antiviral activity and became the first-to-market integrase inhibitor.Compared with other antiviral drugs, it has new action mechanism and target site, so there is no cross resistance between it and them, which makes it a good option for patients with multi-drug resistant HIV strains. HIV infection is very common in hemophiliac patients who need continuous infusion of clotting products,and the chance of getting HIV infection for hemophilia patients is very high, especially before 1985 when non-virus-inactivated factor concentrates were widely used. Many hemophilia patients were infected with HIV, and AIDS became their main cause of death.The recommended first-line antiretroviral regimen for HIV/AIDS patients with hemophilia concludes two NRTIs and one NNRTIs, while protease inhibitors are not recommended to use in these patients, because they are likely to worsen bleeding tendency. So, if HIV/AIDS patients with hemophilia are resistant to NRTIs and NNRTIs, there are few remaining options for them to choose as part of second-line drugs. However, MK-0518，a drug with novel anti-HIV mechanism different with NRTIs and NNRTIs, may be used in HIV/AIDS patients with hemophilia as the second-line drug.

3． Study design

1. Patients Enrollment

2. Patients enrolled in the study sign consent form

3. Select an optimized background therapy(OBT) for each subject

4. Randomization: patients are randomly assigned to MK-0518 400 mg twice daily plus OBT group or placebo plus OBT group, each group concludes at least 50 subjects.

5. Data collection: for each patient, detection of HIV viral load and CD4+ T lymphocyte count is done at screening, and at weeks4, 8, 12, 16, and 24. The safety profile of MK-0518 is monitored according to patients' complaints and the results of physical and laboratory examinations.

6. Endpoints of study: The primary endpoint is the the safety and tolerability of MK-0518 400 mg b.i.d. compared to placebo, both in combination with OBT.The secondary endpoint is antiretroviral activity of MK-0518 400 mg b.i.d. compared to placebo, both in combination with OBT.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: May 2011
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• HIV-infected patients with hemophilia aged over 18 who have failed previous antiretroviral treatment are eligible.

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Hemophilia A
• HIV Infection

Locations

Country	Name	City	State
China	Shanghai Public Health Clinical Center	Shanghai	Jinshan

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai Public Health Clinical Center	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The safety and tolerability of MK-0518 400 mg b.i.d. compared to placebo, both in combination with OBT, assessed by review of the accumulated safety data in HIV-infected patients with hemophilia.		24 weeks	Yes
Secondary	Antiretroviral activity of MK-0518 400 mg b.i.d. compared to placebo, both in combination with OBT.		24 weeks	No