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Use of ACTIMMUNE in Patients With ADO2

Primary Purpose

Autosomal Dominant Osteopetrosis Type 2

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

ACTIMMUNE

About this trial

This is an interventional treatment trial for Autosomal Dominant Osteopetrosis Type 2

Eligibility Criteria

3 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
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
Ages 3 to 65 years inclusive.
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:

Any unstable illness that in the investigator's opinion precludes participation in the study.
Serum calcium >10.6 mg/dl at screening.
eGFR using the MDRD equation in adults (or the modified Schwartz equation for children) of < 35 ml/min/1.73m2.
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

= Faint hyperechogenic rim around the sides and tip of the medullary pyramids
= More intense echogenic rim with echoes faintly filling the entire medullary pyramid
= Intense echoes throughout the medullary pyramid
= 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.

Sites / Locations

Indiana University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

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

Outcomes

Primary Outcome Measures

Changes in Bone Resorption Markers From Baseline to 14 Weeks.

Evaluate for changes in bone resorption markers including CTX, NTX/creatinine ratio between baseline and 14 weeks

Secondary Outcome Measures

Change in Bone Turnover Markers Between After Completion of 6-12 Weeks of Treatment

Evaluate for changes in bone turnover markers including TRAP5b, NTX, CTX/TRAP5b ratio after 6-12 weeks of treatment.

Full Information

NCT ID

NCT02584608

First Posted

October 20, 2015

Last Updated

December 11, 2020

Sponsor

Indiana University

Collaborators

Horizon Pharma Ireland, Ltd., Dublin Ireland

1. Study Identification

Unique Protocol Identification Number

NCT02584608

Brief Title

Use of ACTIMMUNE in Patients With ADO2

Official Title

Phase 2a Study of Interferon Gamma-1b for the Treatment of Autosomal Dominant Type 2 Osteopetrosis

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Completed

Study Start Date

January 1, 2016 (Actual)

Primary Completion Date

November 12, 2019 (Actual)

Study Completion Date

November 12, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Indiana University

Collaborators

Horizon Pharma Ireland, Ltd., Dublin Ireland

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Autosomal Dominant Osteopetrosis Type 2

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

ACTIMMUNE

Primary Outcome Measure Information:

Title

Changes in Bone Resorption Markers From Baseline to 14 Weeks.

Description

Evaluate for changes in bone resorption markers including CTX, NTX/creatinine ratio between baseline and 14 weeks

Time Frame

baseline, 14 weeks

Secondary Outcome Measure Information:

Title

Change in Bone Turnover Markers Between After Completion of 6-12 Weeks of Treatment

Description

Evaluate for changes in bone turnover markers including TRAP5b, NTX, CTX/TRAP5b ratio after 6-12 weeks of treatment.

Time Frame

6-12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

3 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. 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 Ages 3 to 65 years inclusive. 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: Any unstable illness that in the investigator's opinion precludes participation in the study. Serum calcium >10.6 mg/dl at screening. eGFR using the MDRD equation in adults (or the modified Schwartz equation for children) of < 35 ml/min/1.73m2. 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 = Faint hyperechogenic rim around the sides and tip of the medullary pyramids = More intense echogenic rim with echoes faintly filling the entire medullary pyramid = Intense echoes throughout the medullary pyramid = 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael J Econs, MD

Organizational Affiliation

Indiana University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Indiana University School of Medicine

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

30889272

Citation

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.

Results Reference

result

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Use of ACTIMMUNE in Patients With ADO2

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