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

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ClinicalTrials.gov Identifier: NCT00324025
Recruitment Status : Terminated
First Posted : May 10, 2006
Last Update Posted : December 12, 2008
Sponsor:
Information provided by:
Novartis

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.

Condition or disease Intervention/treatment Phase
Cryptococcal Meningitis Drug: Mycograb Drug: placebo Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Mycograb® as Adjunctive Therapy for Cryptococcal Meningitis in Patients With AIDS
Study Start Date : March 2007
Actual Primary Completion Date : September 2007
Actual Study Completion Date : September 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Meningitis
U.S. FDA Resources

Arm Intervention/treatment
Experimental: 1
Mycograb
Drug: Mycograb
Active Comparator: 2
biological
Drug: placebo



Primary Outcome Measures :
  1. proportion of patients cured (combined clinical and microbiological response) versus placebo [ Time Frame: Day 14 ]

Secondary Outcome Measures :
  1. Safety of Mycograb versus placebo. Safety assessment will include: physical examination, vital signs, laboratory parameters, adverse events, serious adverse events. [ Time Frame: Week 10 ]
  2. Assess the cerebrospinal fluid (CSF) penetration of Mycograb [ Time Frame: Days 3, 7 and 14 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Other protocol-defined inclusion/exclusion criteria may apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00324025


Locations
United States, Alabama
University of Alabama School of Medicine
Birmingham, Alabama, United States, 35233
United States, Texas
Department of Medicine/Infectious Disease, MC 7881, University of Texas Health Science Center
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals, MD Novartis Pharmaceuticals

Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00324025     History of Changes
Obsolete Identifiers: NCT00804635
Other Study ID Numbers: MYC123A2202
NTP/Mycograb/003A
First Posted: May 10, 2006    Key Record Dates
Last Update Posted: December 12, 2008
Last Verified: December 2008

Keywords provided by Novartis:
Cryptococcal meningitis

Additional relevant MeSH terms:
Meningitis
Meningitis, Cryptococcal
Central Nervous System Diseases
Nervous System Diseases
Meningitis, Fungal
Central Nervous System Fungal Infections
Mycoses
Cryptococcosis
Central Nervous System Infections
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs