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

Phase 2TerminatedNCT00847678

Novartis Pharmaceuticals38 enrolled

Overview

This is a multicenter, randomized, efficacy and safety trial to evaluate Mycograb®. Subjects will be randomized to one of the 3 arms: 1/ Amphotericin B (0.7 mg/kg/d) plus 5-flucytosine (100 mg /kg/d); 2/ Amphotericin B plus Mycograb® (dosed 1 mg/kg via a central line or peripheral venous line twice daily for 7 consecutive days); 3/ Amphotericin B plus 5-flucytosine plus Mycograb® (dosed 1 mg/kg via a central line or peripheral venous line twice daily for 7 consecutive days). After 2 weeks, all patients will be switched to fluconazole at 400 mg/d for 8 weeks and 200 mg/d thereafter. The total duration of the study will be approximately 24 months

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Cryptococcal Meningitis

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

proportion of patients (receiving Mycograb + Amphotericin B + 5-flucytosine) cured (combined clinical and microbiological response) versus placebo (Amphotericin B + 5-flucytosine) and versus Mycograb + Amphotericin B alone.

Time frame: day 14

Secondary Outcomes

Safety of Mycograb versus placebo. Safety assessment will include: physical examination, vital signs, laboratory parameters, adverse events, serious adverse events.

Time frame: week 10

Assess the cerebrospinal fluid (CSF) penetration of Mycograb

Time frame: Days 3, 7 and 14

Determine whether Mycograb + Amphotericin B is as effective as Amphotericin B plus 5-cytosine while avoiding the potential problem of 5-cytosine toxicity.

Time frame: Day 14