Efficacy and Safety of Mycograb as Adjunctive Therapy for Cryptococcal Meningitis in Patients With AIDS

NCT ID: NCT00324025

Last Updated: 2008-12-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2007-09-30

Brief Summary

This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter efficacy and safety trial to evaluate Mycograb®. Subjects will be randomized to receive either Mycograb® (dosed 1 mg/kg) or placebo during the first week of induction therapy (amphotericin B plus 5-flucytosine) via a central line or peripheral venous line twice daily for 7 consecutive days. The total duration of the study will be approximately 24 months.

Detailed Description

This multicenter, randomized, double-blind, parallel-group clinical trial is designed to evaluate Mycograb® versus placebo as adjunctive therapy to antifungal induction therapy (amphotericin B plus 5-flucytosine) in subjects who have acute cryptococcal meningitis associated with AIDS. After pre-study screening and baseline assessments and meeting all inclusion criteria, on Day 1 subjects will be randomized to 1 of 2 treatment arms:

Amphotericin B (conventional at 0.7 mg/kg, i.v. once daily) plus 5-flucytosine (100 mg/kg orally daily, divided QID), with placebo.

Amphotericin B (conventional at 0.7 mg/kg, i.v. once daily) plus 5-flucytosine (100 mg/kg orally daily, divided QID), with Mycograb®.

Study medication will be administered via a central line or peripheral venous line twice daily for 7 consecutive days (Days 1-7). A lumbar puncture with CSF culture colony counts, India ink microscopy, and measurement of cryptococcal antigen (CrAg) will be performed at Baseline, Days 3, 7, and 14,. CSF will also be assayed for concentrations of Mycograb® on Days 3, 7, and 14. The primary efficacy parameter will be the proportion of subjects considered cured at day 14 (combined clinical AND mycological outcome).

A complimentary clinical trial will be run in parallel with this study in South America and South Africa. The protocol used will be essentially as described here except that there will be an additional (3rd) treatment arm (Amphotericin B [conventional at 0.7 mg/kg, i.v. once daily}with Mycograb®)..

An interim analysis will be performed after 30 patients (US and/or non-US) have completed Day 14, for the following reasons:

To evaluate the safety of Mycograb® by reviewing the adverse events classified by the investigator as possibly related to the study drug To adjust the proposed sample size if necessary. A Safety Monitoring Committee and an independent expert will assess the safety profile of Mycograb®.

A total of 40 completed patients are planned for the US. It is estimated that enrollment will require 54 screened and 48 enrolled to achieve 40 completed patients. The total duration of the trial will be approximately 24 months. If the recruitment rate is low in the US, the number from the US may be reduced, having been replaced by patients outside the US where cryptococcosis is more prevalent.

Conditions

Cryptococcal Meningitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

1

Mycograb

Group Type: EXPERIMENTAL

Mycograb

Intervention Type: DRUG

2

biological

Group Type: ACTIVE_COMPARATOR

placebo

Intervention Type: DRUG

Interventions

Mycograb

Intervention Type: DRUG

placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Male or non-pregnant female who is >18 years old, HIV-positive or unknown, with acute, either first or recurrent episode of cryptococcal meningitis Currently on no treatment, or receiving treatment (< 3 days) with either amphotericin B plus 5-flucytosine, or amphotericin B alone. Positive CSF culture for Cryptococcus neoforman. Physical signs and symptoms of meningitis, evidenced by one or more of the following: fever, headache, meningeal signs and neurologic findings.

Exclusion Criteria

Excluded for coma, or significant other medical conditions. Subject has other opportunistic fungal infections that requires other systemic antifungal therapies.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Novartis Pharmaceuticals

Principal Investigators

Novartis Pharmaceuticals, MD

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

University of Alabama School of Medicine

Birmingham, Alabama, United States

Department of Medicine/Infectious Disease, MC 7881, University of Texas Health Science Center

San Antonio, Texas, United States

Countries

United States

Other Identifiers

NTP/Mycograb/003A

Identifier Type: -

Identifier Source: secondary_id

MYC123A2202

Identifier Type: -

Identifier Source: org_study_id

NCT00804635

Identifier Type: -

Identifier Source: nct_alias