Autosomal Dominant Osteopetrosis Type 2Phase 2NCT02584608

Use of ACTIMMUNE in Patients With ADO2

A Phase 2 study testing ACTIMMUNE in people with Autosomal Dominant Osteopetrosis Type 2, run by Indiana University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 3 to 65 years
Conditions the study is for: Autosomal Dominant Osteopetrosis Type 2
What is being tested?: ACTIMMUNE
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 1 siteUnited States
Study dates: 1 Jan 2016to 12 Nov 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 3 to 65 years
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Show all 15Show fewer

= 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Indiana University School of Medicine
Indianapolis, Indiana, 46202

Other trials in United States

About this study

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

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.

Read the 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
Being tested: ACTIMMUNE
Medical subject headings: Osteopetrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ACTIMMUNEDrug

Study groups in NCT02584608
Study group	Role	What they receive
Treatment	Experimental	ACTIMMUNE 50 µg/m2 subcutaneously three times per week (TIW) for 8 weeks Receives: Drug: ACTIMMUNE

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: baseline, 14 weeks

Secondary outcomes (1)

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.
Measured: 6-12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jan 201612 Nov 2019

First posted22 Oct 2015 (estimated)
Study start1 Jan 2016
Primary completion12 Nov 2019
Study completion12 Nov 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Autosomal Dominant Osteopetrosis Type 2Studies of the same condition, open and under way.
More trials run by Indiana UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02584608
Sponsor's protocol ID: 1510340687
Status last verified: Dec 2020
First submitted: 20 Oct 2015
Last updated: 8 Jan 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 30889272

Study at a glance

From the registry record, last updated by the sponsor on 8 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 2a Study of Interferon Gamma-1b for the Treatment of Autosomal Dominant Type 2 Osteopetrosis
ClinicalTrials.gov ID: NCT02584608
Acronym / sponsor ID: 1510340687
Conditions: Autosomal Dominant Osteopetrosis Type 2
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: Indiana UniversityUniversity, hospital or other
Collaborators: Horizon Pharma Ireland, Ltd., Dublin Ireland
Study start: 1 Jan 2016 (actual)
Primary completion: 12 Nov 2019 (actual)
Study completion: 12 Nov 2019 (actual)
First posted: 22 Oct 2015 (estimated)
Results: Posted 8 Jan 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

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.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment	Experimental	Drug: ACTIMMUNEACTIMMUNE 50 µg/m2 subcutaneously three times per week (TIW) for 8 weeks

Who may qualify

Ages: 3 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (15 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ACTIMMUNE	Drug	Treatment

Primary outcome

Changes in Bone Resorption Markers From Baseline to 14 Weeks.
Time frame: baseline, 14 weeks
Evaluate for changes in bone resorption markers including CTX, NTX/creatinine ratio between baseline and 14 weeks

1 secondary outcome

Change in Bone Turnover Markers Between After Completion of 6-12 Weeks of Treatment
Time frame: 6-12 weeks

Results and safety

Results posted to the registry on 8 Jan 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment	12	12

Primary outcome: Changes in Bone Resorption Markers From Baseline to 14 Weeks.

Time frame: baseline, 14 weeks. Mean (Full Range). Unit: percentage of change

Measure	Treatment n = 12
Percent change of CTX	2.2 (-35.7 to 90.5)
Percent change of NTX/creatinine ratio	-2.1 (-50.5 to 55.5)

Population analysed: All subjects

1 secondary outcome is reported in the full results.

Adverse events

Time frame: From signing consent till final followup at 18 weeks (4 weeks after stopping study drug). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment	0 of 12 (0%)	10 of 12 (83.3%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 30889272Imel 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Michael J Econs, MD principal investigator

Indiana University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ACTIMMUNE in people with Autosomal Dominant Osteopetrosis Type 2, run by Indiana University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in Bone Resorption Markers From Baseline to 14 Weeks. (time frame: baseline, 14 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02584608, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2021.