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Safety and Antifungal Activity of Recombinant Interferon-Gamma 1b (rIFN-Gamma 1b) Given With Standard Therapy in Patients With Cryptococcal Meningitis

Primary Purpose

Meningitis, Cryptococcal, HIV Infections

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Itraconazole
Flucytosine
Fluconazole
Amphotericin B
Interferon gamma-1b
Sponsored by
InterMune
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Meningitis, Cryptococcal focused on measuring Interferon-gamma, Recombinant, Injections, Subcutaneous, Itraconazole, Dose-Response Relationship, Drug, Fluconazole, Flucytosine, Antifungal Agents, Amphotericin B, Meningitis, Cryptococcal

Eligibility Criteria

13 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Patients may be eligible for Stage 1 if they: Are at least 13 years old. Have consent of a parent, family member, or guardian if less than 18 years of age. Have cryptococcal meningitis for the first time or have had a relapse. Are not on any medications that cannot be taken with fluconazole or itraconazole, if the patient has trouble taking fluconazole. Patients may be eligible for Stage 2 if they: Had no serious decline in health, as determined by their doctor, during the previous 14 days (including mental health). Have received at least 7.5 mg/kg AMB in Stage 1. Have a positive CSF culture for C. neoformans. Can take oral medications. Exclusion Criteria Patients will not be eligible for this study if they: Are in a coma. Are pregnant or breast-feeding. Are not using effective birth control methods, if able to have children. Are allergic to imidazole or triazole. Are allergic to rIFN-gamma 1b. Require drugs that are toxic to the kidneys, other than AMB. Received erythropoietin or red blood cell transfusions within 4 weeks of entering the study. Are receiving systemic corticosteroid therapy within 30 days of study or will require it during the study. Have had serious heart disease. Have had multiple sclerosis, peripheral vascular disease, or rheumatologic disorders. Have had disorders of the central nervous system (CNS) (not including emotional problems) or a seizure disorder, or have a current CNS disorder that would interfere with the study. Are receiving investigational therapy for C. neoformans within 90 days of starting the study drug. Have had more than 3 doses of AMB or more than 1200 mg of fluconazole or itraconazole as prior treatment and have begun current treatment for more than 72 hours prior to starting study medication. Fluconazole or itraconazole of no more than 200 mg daily is allowed. Are receiving AMB for C. neoformans within 30 days of starting treatment for the present episode. Are receiving rIFN-gamma 1b treatment within 90 days prior to starting the study drug. Have had therapy which affects the immune system within 30 days prior to starting the study drug. Are receiving investigational therapy for all other signs within 30 days prior to starting the study drug. Are not able to meet the study requirements, in the opinion of the investigator. Require chronic treatment with H2-blockers, and are able to receive only itraconazole in Stage 2. Show signs of or get treatment for another serious opportunistic infection within 4 weeks of starting the study drug.

Sites / Locations

  • Univ of Alabama at Birmingham
  • Washington Univ
  • UMDNJ - New Jersey Med School / Cooper Hosp
  • Univ of Med & Dentistry of New Jersey
  • Houston Veterans Administration Med Ctr
  • Univ of Texas / Med School at Houston
  • Audie L Murphy Veterans Administration Hosp
  • Hosp Nacional dos de Mayo
  • Instituto de Medicina Tropical

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
March 9, 2001
Last Updated
May 29, 2009
Sponsor
InterMune
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1. Study Identification

Unique Protocol Identification Number
NCT00012467
Brief Title
Safety and Antifungal Activity of Recombinant Interferon-Gamma 1b (rIFN-Gamma 1b) Given With Standard Therapy in Patients With Cryptococcal Meningitis
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Phase II Study of the Safety and Antifungal Activity of Subcutaneous Recombinant Interferon-Gamma 1b (rIFN-Gamma 1b) in Conjunction With Standard Therapy in Patients With Acute Cryptococcal Meningitis
Study Type
Interventional

2. Study Status

Record Verification Date
May 2009
Overall Recruitment Status
Completed
Study Start Date
January 2000 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
July 2001 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
InterMune

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to examine the antifungal activity of recombinant interferon-gamma 1b (rIFN-gamma 1b) given with standard antifungal therapy.
Detailed Description
Patients are randomized into 1 of 3 parallel groups for a 3-arm, 2-stage, double-blind and dose-ranging study for 14 weeks. In Stage 1, patients are hospitalized for 14 days of acute therapy. Patients receive rIFN-gamma 1b or placebo sc 3 times per week, intravenous (IV) AMB daily, and with or without oral 5-FC every 6 hours. Patients who have the ability to take oral medications, who do not have any significant clinical deterioration during the previous 14 days, and who meet the eligibility criteria can progress to Stage 2. In Stage 2 patients receive 84 days of consolidation therapy (56 days with study drug and 28 days of follow-up). On an outpatient basis, patients receive either placebo or 1 of 2 doses of rIFN-gamma 1b sc 3 times per week, and oral fluconazole daily or oral itraconazole 2 times a day.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Meningitis, Cryptococcal, HIV Infections
Keywords
Interferon-gamma, Recombinant, Injections, Subcutaneous, Itraconazole, Dose-Response Relationship, Drug, Fluconazole, Flucytosine, Antifungal Agents, Amphotericin B, Meningitis, Cryptococcal

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
Double
Enrollment
60 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Itraconazole
Intervention Type
Drug
Intervention Name(s)
Flucytosine
Intervention Type
Drug
Intervention Name(s)
Fluconazole
Intervention Type
Drug
Intervention Name(s)
Amphotericin B
Intervention Type
Drug
Intervention Name(s)
Interferon gamma-1b

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Patients may be eligible for Stage 1 if they: Are at least 13 years old. Have consent of a parent, family member, or guardian if less than 18 years of age. Have cryptococcal meningitis for the first time or have had a relapse. Are not on any medications that cannot be taken with fluconazole or itraconazole, if the patient has trouble taking fluconazole. Patients may be eligible for Stage 2 if they: Had no serious decline in health, as determined by their doctor, during the previous 14 days (including mental health). Have received at least 7.5 mg/kg AMB in Stage 1. Have a positive CSF culture for C. neoformans. Can take oral medications. Exclusion Criteria Patients will not be eligible for this study if they: Are in a coma. Are pregnant or breast-feeding. Are not using effective birth control methods, if able to have children. Are allergic to imidazole or triazole. Are allergic to rIFN-gamma 1b. Require drugs that are toxic to the kidneys, other than AMB. Received erythropoietin or red blood cell transfusions within 4 weeks of entering the study. Are receiving systemic corticosteroid therapy within 30 days of study or will require it during the study. Have had serious heart disease. Have had multiple sclerosis, peripheral vascular disease, or rheumatologic disorders. Have had disorders of the central nervous system (CNS) (not including emotional problems) or a seizure disorder, or have a current CNS disorder that would interfere with the study. Are receiving investigational therapy for C. neoformans within 90 days of starting the study drug. Have had more than 3 doses of AMB or more than 1200 mg of fluconazole or itraconazole as prior treatment and have begun current treatment for more than 72 hours prior to starting study medication. Fluconazole or itraconazole of no more than 200 mg daily is allowed. Are receiving AMB for C. neoformans within 30 days of starting treatment for the present episode. Are receiving rIFN-gamma 1b treatment within 90 days prior to starting the study drug. Have had therapy which affects the immune system within 30 days prior to starting the study drug. Are receiving investigational therapy for all other signs within 30 days prior to starting the study drug. Are not able to meet the study requirements, in the opinion of the investigator. Require chronic treatment with H2-blockers, and are able to receive only itraconazole in Stage 2. Show signs of or get treatment for another serious opportunistic infection within 4 weeks of starting the study drug.
Facility Information:
Facility Name
Univ of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Washington Univ
City
St Louis
State/Province
Missouri
ZIP/Postal Code
63108
Country
United States
Facility Name
UMDNJ - New Jersey Med School / Cooper Hosp
City
Camden
State/Province
New Jersey
ZIP/Postal Code
08103
Country
United States
Facility Name
Univ of Med & Dentistry of New Jersey
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
Facility Name
Houston Veterans Administration Med Ctr
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Univ of Texas / Med School at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Audie L Murphy Veterans Administration Hosp
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78284
Country
United States
Facility Name
Hosp Nacional dos de Mayo
City
Lima
Country
Peru
Facility Name
Instituto de Medicina Tropical
City
Lima
Country
Peru

12. IPD Sharing Statement

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Safety and Antifungal Activity of Recombinant Interferon-Gamma 1b (rIFN-Gamma 1b) Given With Standard Therapy in Patients With Cryptococcal Meningitis

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