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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
Sponsored by
Indiana University
About
Eligibility
Locations
Arms
Outcomes
Full info

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:

  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.

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

First Posted
October 20, 2015
Last Updated
December 11, 2020
Sponsor
Indiana University
Collaborators
Horizon Pharma Ireland, Ltd., Dublin Ireland
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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
No
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
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Use of ACTIMMUNE in Patients With ADO2

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