Clinical Trial: ACTIMMUNE in Intermediate Osteopetrosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Open-label Early Phase 2 Study With a Single Arm of Interferon Gamma-1b Treatment of Osteopetrosis

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.

Detailed Summary:

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 pat
    Sponsor: Los Angeles Biomedical Research Institute

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

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Change in Bone Mineral Density (BMD) [ Time Frame: 12 months ]
      BMD measured by peripheral quantitative computed tomography (pQCT)
    • Change in white blood cell count (WBC) [ Time Frame: 12 months ]
    • Change in pain score [ Time Frame: 4 weeks ]
      Self reported pain intensity over the last 4 weeks


    Original Secondary Outcome: Same as current

    Information By: Los Angeles Biomedical Research Institute

    Dates:
    Date Received: June 23, 2015
    Date Started: February 2016
    Date Completion: January 2019
    Last Updated: May 3, 2017
    Last Verified: April 2017