Use of ACTIMMUNE in Patients With ADO2

NCT ID: NCT02584608

Last Updated: 2021-01-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-01
• Study Completion Date: 2019-11-12

Brief 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.

Detailed Description

This is a single center, open-label, dose-escalation study evaluating the efficacy, as defined by biochemical endpoints, and safety profiles of ACTIMMUNE in ADO2 subject.

The investigators will treat 12 ADO2 subjects (children or adults age 3-65) with Actimmune® via a dose escalation protocol to a dose of 50 µg/m2 subcutaneously three times per week (TIW) for 8 weeks. If serum CTX does not increase by more than 25% by week 8, the dose will be increased to 100 µg/m2 subcutaneously TIW.

Individual subjects in whom ACTIMMUNE administration increases bone resorption markers during the 14 weeks of this trial will be eligible for a 1 year extension trial.

Conditions

Autosomal Dominant Osteopetrosis Type 2

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

ACTIMMUNE 50 µg/m2 subcutaneously three times per week (TIW) for 8 weeks

Group Type: EXPERIMENTAL

ACTIMMUNE

Intervention Type: DRUG

Interventions

ACTIMMUNE

Intervention Type: DRUG

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.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Horizon Pharma Ireland, Ltd., Dublin Ireland

INDUSTRY

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Michael Econs

MD, Professor of Endocrinlogy and Metabolism

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael J Econs, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Locations

Indiana University School of Medicine

Indianapolis, Indiana, United States

Countries

United States

References

Imel EA, Liu Z, Acton D, Coffman M, Gebregziabher N, Tong Y, Econs MJ. Interferon Gamma-1b Does Not Increase Markers of Bone Resorption in Autosomal Dominant Osteopetrosis. J Bone Miner Res. 2019 Aug;34(8):1436-1445. doi: 10.1002/jbmr.3715. Epub 2019 May 13.

Reference Type: RESULT

PMID: 30889272 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1510340687

Identifier Type: -

Identifier Source: org_study_id