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

Study Description

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Brief 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.

Condition or disease
HIV Infection; Hemophilia A

Detailed 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.

Study Design

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Study Type :	Observational
Estimated Enrollment :	100 participants
Observational Model:	Case Control
Time Perspective:	Prospective
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
Study Start Date :	May 2009
Estimated Primary Completion Date :	October 2010
Estimated Study Completion Date :	May 2011

Groups and Cohorts

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort
1
2

Outcome Measures

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. 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. [ Time Frame: 24 weeks ]

Secondary Outcome Measures :

1. Antiretroviral activity of MK-0518 400 mg b.i.d. compared to placebo, both in combination with OBT. [ Time Frame: 24 weeks ]

Biospecimen Retention:   Samples Without DNA

3 ml plasm of each subject on week 4,8,12 and 24

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

treatment-experienced HIV-1 infected adult patients with hemophilia

Criteria

Inclusion Criteria:

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

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Hongzhou Lu, PhD	0086-2157248758	luhongzhou@fudan.edu.cn

Locations

China, Jinshan
Shanghai Public Health Clinical Center	Not yet recruiting
Shanghai, Jinshan, China, 201508
Contact: Hongzhou Lu, PhD 0086-2157248758 luhongzhou@fudan.edu.cn
Principal Investigator: Hongzhou Lu, PhD

Sponsors and Collaborators

Shanghai Public Health Clinical Center

Merck Sharp & Dohme Corp.

Investigators

Principal Investigator:	Hongzhou Lu, PhD	Shanghai Public Health Clinical Center

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Shanghai Public Health Clinical Center
ClinicalTrials.gov Identifier:	NCT00797381 History of Changes
Other Study ID Numbers:	CN2009
First Posted:	November 25, 2008
Last Update Posted:	November 25, 2008
Last Verified:	November 2008

Keywords provided by Shanghai Public Health Clinical Center:

MK-0518; HIV; AIDS; hemophilia; treatment experienced

Additional relevant MeSH terms:

HIV Infections; Hemophilia A; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases	Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Raltegravir Potassium; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action