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

This study has been completed.
Sponsor:
Information provided by:
InterMune
ClinicalTrials.gov Identifier:
NCT00012467
First received: March 9, 2001
Last updated: May 29, 2009
Last verified: May 2009
  Purpose

The purpose of this study is to examine the antifungal activity of recombinant interferon-gamma 1b (rIFN-gamma 1b) given with standard antifungal therapy.


Condition Intervention Phase
Meningitis, Cryptococcal
HIV Infections
Drug: Itraconazole
Drug: Flucytosine
Drug: Fluconazole
Drug: Amphotericin B
Drug: Interferon gamma-1b
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Masking: Double-Blind
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by InterMune:

Estimated Enrollment: 60
Study Start Date: January 2000
Study Completion Date: July 2001
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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00012467

Locations
United States, Alabama
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Missouri
Washington Univ
St Louis, Missouri, United States, 63108
United States, New Jersey
UMDNJ - New Jersey Med School / Cooper Hosp
Camden, New Jersey, United States, 08103
Univ of Med & Dentistry of New Jersey
Newark, New Jersey, United States, 07103
United States, Texas
Houston Veterans Administration Med Ctr
Houston, Texas, United States, 77030
Univ of Texas / Med School at Houston
Houston, Texas, United States, 77030
Audie L Murphy Veterans Administration Hosp
San Antonio, Texas, United States, 78284
Peru
Instituto de Medicina Tropical
Lima, Peru
Hosp Nacional dos de Mayo
Lima, Peru
Sponsors and Collaborators
InterMune
  More Information

No publications provided

Responsible Party: Steven Porter, MD, PhD, InterMune Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT00012467     History of Changes
Other Study ID Numbers: B013, GIMY-001
Study First Received: March 9, 2001
Last Updated: May 29, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by InterMune:
Interferon-gamma, Recombinant
Injections, Subcutaneous
Itraconazole
Dose-Response Relationship, Drug
Fluconazole
Flucytosine
Antifungal Agents
Amphotericin B
Meningitis, Cryptococcal

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Meningitis
Meningitis, Cryptococcal
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Meningitis, Fungal
Central Nervous System Fungal Infections
Mycoses
Cryptococcosis
Interferons
Interferon-gamma
Hydroxyitraconazole
Liposomal amphotericin B
Fluconazole
Itraconazole
Amphotericin B
Miconazole
Flucytosine
Antifungal Agents

ClinicalTrials.gov processed this record on October 01, 2014