We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

ACTIMMUNE in Intermediate Osteopetrosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02666768
Recruitment Status : Completed
First Posted : January 28, 2016
Last Update Posted : July 2, 2019
University of Minnesota
Horizon Pharma Ireland, Ltd., Dublin Ireland
Information provided by (Responsible Party):
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Brief Summary:
This study evaluates the effects of ACTIMMUNE (IFN-γ1b) in children and adults with intermediate osteoporosis. All participants will receive treatment with ACTIMMUNE for 12 months. The investigators hypothesize that ACTIMMUNE will be tolerated by participants for the full 12 months and result in decreased disease severity.

Condition or disease Intervention/treatment Phase
Osteopetrosis Drug: Interferon gamma-1b Phase 2

Detailed Description:

Osteopetrosis is a rare inherited metabolic bone disease characterized by impaired osteoclast function resulting in defective bone resorption and generalized high bone mass and mineral density (BMD). In patients with severe disease, this high bone mass compromises bone marrow space leading to marrow failure and frequent infections, along with hepatosplenomegaly from extramedullary hematopoiesis. Currently, the only treatment for individuals with severe forms of osteopetrosis is hematopoietic cell transplantation (HCT), however survival in patients with osteopetrosis treated with HCT is only around 55%. Therefore, this treatment is only indicated in select individuals with life-threatening complications of their disease. Thus additional treatments for osteopetrosis are needed both for individuals who are not candidates for HCT and to prolong the time until HCT is needed.

Interferon gamma (IFN-γ) is a naturally occurring cytokine that has been shown to have anti-microbial and anti-viral immunomodulatory effects, and is a potent stimulator of superoxide anion production which in turn promotes the formation and activation of osteoclasts. Two previous studies of IFN-γ1b in a small group of individuals with osteopetrosis found a decrease in trabecular bone area, an increase in marrow space, a decrease in the number of severe infections requiring antibiotic therapy, and an increase in superoxide generation by granulocyte-macrophage colonies.

Therefore, the investigators will conduct an early phase 2, multi-center, open-label, 12-month clinical trial of ACTIMMUNE (IFN-γ1b) treatment of patients with intermediate osteopetrosis to determine the following:

  1. The feasibility and tolerability of interferon gamma-1b treatment for 1 year in patients with intermediate osteopetrosis. Specifically, i) the ability to enroll patients, and ii) continued treatment throughout the 1-year observational period.
  2. Change in immunologic and hematologic function, bone mineral density and osteoclast function, physical function and quality of life.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-label Early Phase 2 Study With a Single Arm of Interferon Gamma-1b Treatment of Osteopetrosis
Actual Study Start Date : February 22, 2016
Actual Primary Completion Date : March 11, 2019
Actual Study Completion Date : April 11, 2019

Arm Intervention/treatment
Experimental: gamma interferon-1b
Gamma interferon-1b 100 mcg SC 3 times weekly for 12 months
Drug: Interferon gamma-1b
gamma interferon-1b dose escalation over first 4 weeks of study to 100 mcg SC 3 times weekly

Primary Outcome Measures :
  1. Number of participants with treatment related adverse events CTCAE v4.0 Grade 3 or higher [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Change in Bone Mineral Density (BMD) [ Time Frame: 12 months ]
    BMD measured by peripheral quantitative computed tomography (pQCT)

  2. Change in white blood cell count (WBC) [ Time Frame: 12 months ]
  3. Change in pain score [ Time Frame: 4 weeks ]
    Self reported pain intensity over the last 4 weeks

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   1 Year and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of osteopetrosis; and
  • Anemia (Hemoglobin <12 g/dL) not related to iron deficiency, or
  • Neutropenia (Neutrophil count <1000 neutrophils/ul unsupported with cytokines), or
  • Thrombocytopenia (Platelet count <50,000 cells x 109/L), or
  • History of impaired bone healing, or
  • ≥ 1 serious infection over prior year defined as requiring hospitalization and/or IV antibiotics, and
  • Age > 1 year; and
  • Ability to travel to a study center for every 3-6 month study visits; and
  • Patient or parent/legal guardian is able and willing to provide informed consent. For patients 7 to 17 years of age, assent must also be provided.

Exclusion Criteria:

  • 12 months or fewer following HCT;
  • Pregnancy or breastfeeding;
  • Known or suspected allergy to interferon gamma-1b or related products;
  • Participation in simultaneous therapeutic study that involves an investigational study drug or agent within 4 weeks of study enrollment;
  • ALT greater than 3 fold higher than normal; or
  • Any other social or medical condition that the Investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated or be detrimental to the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02666768

Layout table for location information
United States, California
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Torrance, California, United States, 90502
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55454
Sponsors and Collaborators
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
University of Minnesota
Horizon Pharma Ireland, Ltd., Dublin Ireland
Layout table for investigator information
Principal Investigator: Lynda E Polgreen, MD, MS Los Angeles BioMedical Research Center at Harbor-UCLA
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
ClinicalTrials.gov Identifier: NCT02666768    
Other Study ID Numbers: 21549-01
First Posted: January 28, 2016    Key Record Dates
Last Update Posted: July 2, 2019
Last Verified: June 2019
Additional relevant MeSH terms:
Layout table for MeSH terms
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents