Efficacy and Safety of Mycograb as Adjunctive Therapy for Cryptococcal Meningitis in Patients With AIDS
Information source: Novartis
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cryptococcal Meningitis
Intervention: Mycograb (Drug); placebo (Drug)
Phase: Phase 2
Status: Terminated
Sponsored by: Novartis Pharmaceuticals Official(s) and/or principal investigator(s): Novartis Pharmaceuticals, MD, Study Director, Affiliation: Novartis Pharmaceuticals
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.
Clinical Details
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 design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Primary outcome: proportion of patients cured (combined clinical and microbiological response) versus placebo
Secondary outcome: Safety of Mycograb versus placebo. Safety assessment will include: physical examination, vital signs, laboratory parameters, adverse events, serious adverse events.Assess the cerebrospinal fluid (CSF) penetration of Mycograb
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
University of Alabama School of Medicine, Birmingham, Alabama 35233, United States
Department of Medicine/Infectious Disease, MC 7881, University of Texas Health Science Center, San Antonio, Texas 78229, United States
Additional Information
Starting date: March 2007
Last updated: December 11, 2008
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