Cryptococcal Meningitis
Conditions
Keywords
Cryptococcal Meningitis
Brief summary
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
Interventions
BIOLOGICALEfungumab (Mycograb)
BIOLOGICALplacebo
BIOLOGICALAmphotericin B
BIOLOGICAL5 flucytosine
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. | day 14 |
Secondary
| Measure | Time frame |
|---|---|
| Safety of Mycograb versus placebo. Safety assessment will include: physical examination, vital signs, laboratory parameters, adverse events, serious adverse events. | week 10 |
| Assess the cerebrospinal fluid (CSF) penetration of Mycograb | 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. | Day 14 |
Countries
South Africa
Outcome results
None listed