Use of ACTIMMUNE in Patients With ADO2
Condition: Autosomal Dominant Osteopetrosis Type 2
MeSH terms: Osteopetrosis
Intervention: ACTIMMUNE
Intervention MeSH terms: Interferon-gamma
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 3 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This study is an open label use of ACTIMMUNE for patients with Autosomal Dominant
      Osteopetrosis Type 2(ADO2). Effects of treatment will be evaluated after 14 weeks on
      ACTIMMUNE by bone resorption markers. This study will treat 12 patients with ADO2 recruited
      from Indiana University and Riley Hospital for Children at Indiana University Health.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject is diagnosed with clinically significant ADO2 as determined by the
             investigator.

             Individuals will be screened who have either been diagnosed with osteopetrosis and
             have a clinical phenotype and/or family history that is consistent with ADO2, have
             been told that they have an abnormally high bone density (>3SD above mean for age and
             sex), or a clinical presentation consistent with ADO2. Initial contact will be with
             members of ADO2 kindreds who have known disease.

          2. Provide written informed consent for competent adults and for minors provide written
             assent (if appropriate) and written informed consent by a legally authorized
             representative after the nature of the study has been explained, and prior to any
             research-related procedures

          3. Ages 3 to 65 years inclusive.

          4. Willing to use reliable method of contraception [i.e. oral or patch hormonal
             contraceptives, intrauterine device, physical barrier methods, tubal ligation or
             hysterectomy, vasectomy (partner) or abstinence] throughout the study and for 30 days
             after the last dose of study drug.

        Exclusion Criteria:

          1. Any unstable illness that in the investigator's opinion precludes participation in the
             study.

          2. Serum calcium >10.6 mg/dl at screening.

          3. eGFR using the MDRD equation in adults (or the modified Schwartz equation for
             children) of < 35 ml/min/1.73m2.

          4. Nephrocalcinosis on screening ultrasound Grade 3 or higher [18]. Subjects with grade 3
             or higher nephrocalcinosis will be excluded because we anticipate that use of study
             drug will increase bone resorption, resulting in increased urinary calcium excretion,
             which could, potentially, lead to worsening nephrocalcinosis. The grading scale is
             listed below:

        0 = Normal

          1. = Faint hyperechogenic rim around the sides and tip of the medullary pyramids

          2. = More intense echogenic rim with echoes faintly filling the entire medullary pyramid

          3. = Intense echoes throughout the medullary pyramid

          4. = Solitary focus of echoes at the tip of the medullary pyramid/nephrolithiasis

        5. Use of any investigational product (drug or device) within 30 days prior to
        randomization.

        6. Subject reported history of hepatitis C.

        7. A recent (past 5 years) history of alcoholism or intravenous drug abuse.

        8. History of hypersensitivity to IFN-ɣ or E. coli-derived products.

        9. History of liver disease as evidenced by laboratory results at Screening (aspartate
        aminotransferase [AST] or alanine aminotransferase [ALT] >2x the upper limit of normal),
        except when in the opinion of the investigator the liver disease is caused by extra
        medullary hematopoiesis.

        10. Pregnant or nursing women or those who plan on becoming pregnant during the study.