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

This study has been terminated.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00324025
First received: May 8, 2006
Last updated: December 11, 2008
Last verified: December 2008

May 8, 2006
December 11, 2008
March 2007
September 2007   (final data collection date for primary outcome measure)
proportion of patients cured (combined clinical and microbiological response) versus placebo [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00324025 on ClinicalTrials.gov Archive Site
  • Safety of Mycograb versus placebo. Safety assessment will include: physical examination, vital signs, laboratory parameters, adverse events, serious adverse events. [ Time Frame: Week 10 ] [ Designated as safety issue: Yes ]
  • Assess the cerebrospinal fluid (CSF) penetration of Mycograb [ Time Frame: Days 3, 7 and 14 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Efficacy and Safety of Mycograb as Adjunctive Therapy for Cryptococcal Meningitis in Patients With AIDS
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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Cryptococcal Meningitis
  • Drug: Mycograb
  • Drug: placebo
    Other Name: placebo
  • Experimental: 1
    Mycograb
    Intervention: Drug: Mycograb
  • Active Comparator: 2
    biological
    Intervention: Drug: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
3
September 2007
September 2007   (final data collection date for primary outcome measure)

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

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00324025
MYC123A2202, NTP/Mycograb/003A
Not Provided
External Affairs, Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals, MD Novartis Pharmaceuticals
Novartis
December 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP