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

Study Overview
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Brief Summary
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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

Official Title
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A Multicenter, Randomized Study to Assess the Efficacy and Safety of Mycograb® as Adjunctive Therapy for Cryptococcal Meningitis in Patients With AIDS

Conditions
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Cryptococcal Meningitis

Intervention / Treatment
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* Biological: Efungumab (Mycograb)
* Biological: placebo
* Biological: Amphotericin B
* Biological: 5 flucytosine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Mycograb + Amphotericin B + 5 flucytosine | Biological: Efungumab (Mycograb)<br> <br> Biological: Amphotericin B<br> <br> Biological: 5 flucytosine<br> <br> |
| Placebo Comparator: 2<br>Placebo + Amphotericin B + 5 flucytosine | Biological: placebo<br> <br> Biological: Amphotericin B<br> <br> Biological: 5 flucytosine<br> <br> |
| Experimental: 3<br>Mycograb + Amphotericin B | Biological: Efungumab (Mycograb)<br> <br> Biological: Amphotericin B<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cryptococcal Meningitis