OsteopetrosisPhase 2NCT02666768
ACTIMMUNE in Intermediate Osteopetrosis
A Phase 2 study testing Interferon gamma-1b in people with Osteopetrosis, run by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center at 2 sites in United States.
Trial summary
This study evaluates the effects of ACTIMMUNE (IFN-γ1b) in children and adults with intermediate osteoporosis. All participants will receive treatment with ACTIMMUNE for 12 months. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Osteopetrosis
- What is being tested?
- Interferon gamma-1b
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 2 sitesUnited States
- Study dates
- 22 Feb 2016to 11 Apr 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 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of osteopetrosis; and
- Anemia (Hemoglobin <12 g/dL) not related to iron deficiency, or
- Neutropenia (Neutrophil count <1000 neutrophils/ul unsupported with cytokines), or
- Thrombocytopenia (Platelet count <50,000 cells x 109/L), or
- History of impaired bone healing, or
- ≥ 1 serious infection over prior year defined as requiring hospitalization and/or IV antibiotics, and
Show all 9Show fewer
- Age > 1 year; and
- Ability to travel to a study center for every 3-6 month study visits; and
- Patient or parent/legal guardian is able and willing to provide informed consent. For patients 7 to 17 years of age, assent must also be provided.
Who cannot join
- 12 months or fewer following HCT;
- Pregnancy or breastfeeding;
- Known or suspected allergy to interferon gamma-1b or related products;
- Participation in simultaneous therapeutic study that involves an investigational study drug or agent within 4 weeks of study enrollment;
- ALT greater than 3 fold higher than normal; or
- Any other social or medical condition that the Investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated or be detrimental to the study.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Minnesota
Minneapolis, Minnesota, 55454
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Torrance, California, 90502
About this study
Official title: Open-label Early Phase 2 Study With a Single Arm of Interferon Gamma-1b Treatment of Osteopetrosis
This study evaluates the effects of ACTIMMUNE (IFN-γ1b) in children and adults with intermediate osteoporosis. All participants will receive treatment with ACTIMMUNE for 12 months. The investigators hypothesize that ACTIMMUNE will be tolerated by participants for the full 12 months and result in decreased disease severity.
Read the detailed description
Osteopetrosis is a rare inherited metabolic bone disease characterized by impaired osteoclast function resulting in defective bone resorption and generalized high bone mass and mineral density (BMD). In patients with severe disease, this high bone mass compromises bone marrow space leading to marrow failure and frequent infections, along with hepatosplenomegaly from extramedullary hematopoiesis. Currently, the only treatment for individuals with severe forms of osteopetrosis is hematopoietic cell transplantation (HCT), however survival in patients with osteopetrosis treated with HCT is only around 55%. Therefore, this treatment is only indicated in select individuals with life-threatening complications of their disease. Thus additional treatments for osteopetrosis are needed both for individuals who are not candidates for HCT and to prolong the time until HCT is needed.
Interferon gamma (IFN-γ) is a naturally occurring cytokine that has been shown to have anti-microbial and anti-viral immunomodulatory effects, and is a potent stimulator of superoxide anion production which in turn promotes the formation and activation of osteoclasts. Two previous studies of IFN-γ1b in a small group of individuals with osteopetrosis found a decrease in trabecular bone area, an increase in marrow space, a decrease in the number of severe infections requiring antibiotic therapy, and an increase in superoxide generation by granulocyte-macrophage colonies.
Therefore, the investigators will conduct an early phase 2, multi-center, open-label, 12-month clinical trial of ACTIMMUNE (IFN-γ1b) treatment of patients with intermediate osteopetrosis to determine the following:
- The feasibility and tolerability of interferon gamma-1b treatment for 1 year in patients with intermediate osteopetrosis. Specifically, i) the ability to enroll patients, and ii) continued treatment throughout the 1-year observational period.
- Change in immunologic and hematologic function, bone mineral density and osteoclast function, physical function and quality of life.
- Conditions
- Osteopetrosis
- Being tested
- Interferon gamma-1b
- Medical subject headings
- Osteopetrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interferon gamma-1bDrug
Also called ACTIMMUNE
gamma interferon-1b dose escalation over first 4 weeks of study to 100 mcg SC 3 times weekly
| Study group | Role | What they receive |
|---|---|---|
| gamma interferon-1b | Experimental | Gamma interferon-1b 100 mcg subcutaneous (SC) 3 times weekly for 12 months Receives: Drug: Interferon gamma-1b |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Related Adverse Events CTCAE v4.0 Grade 3 or Higher
Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 defines a Grade 4 event as having life-threatening consequences, and/or urgent intervention indicated.
Measured: 12 months
Secondary outcomes (3)
Percent Change From Baseline in Bone Mineral Density (BMD)
BMD measured by peripheral quantitative computed tomography (pQCT) in bone area w/ BMD<169mg/m3
Measured: 6 months
Change From Baseline in White Blood Cell Count (WBC)
Measured: 6 months
Change From Baseline in Pain
Survey name: RAND 36-Item Health Survey (Version 1.0) Scale name: Pain Scale range: 0-100; Higher score means less pain
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2016 (estimated)
- Study start22 Feb 2016
- Primary completion11 Mar 2019
- Study completion11 Apr 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 OsteopetrosisStudies of the same condition, open and under way.
- 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
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Minnesota, Horizon Pharma Ireland, Ltd., Dublin Ireland
- Responsible party
- Principal investigator, Lynda E Polgreen, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Investigators
- Lynda E Polgreen, MD, MS, Principal investigator, Los Angeles BioMedical Research Center at Harbor-UCLA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02666768
- Sponsor's protocol ID
- 21549-01
- Status last verified
- Oct 2024
- First submitted
- 23 Jun 2015
- Last updated
- 22 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Lertwilaiwittaya P, Suktitipat B, Khongthon P, Pongsapich W, Limwongse C, Pithukpakorn M. Identification of novel mutation in RANKL by whole-exome sequencing in a Thai family with osteopetrosis; a case report and review of RANKL osteopetrosis. Mol Genet Genomic Med. 2021 Jul;9(7):e1727. doi: 10.1002/mgg3.1727. Epub 2021 May 30.
PubMed 34056870
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label Early Phase 2 Study With a Single Arm of Interferon Gamma-1b Treatment of Osteopetrosis
- ClinicalTrials.gov ID
- NCT02666768
- Acronym / sponsor ID
- 21549-01
- Conditions
- Osteopetrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterUniversity, hospital or other
- Collaborators
- University of Minnesota, Horizon Pharma Ireland, Ltd., Dublin Ireland
- Study start
- 22 Feb 2016 (actual)
- Primary completion
- 11 Mar 2019 (actual)
- Study completion
- 11 Apr 2019 (actual)
- First posted
- 28 Jan 2016 (estimated)
- Results
- Posted 11 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the effects of ACTIMMUNE (IFN-γ1b) in children and adults with intermediate osteoporosis. All participants will receive treatment with ACTIMMUNE for 12 months. The investigators hypothesize that ACTIMMUNE will be tolerated by participants for the full 12 months and result in decreased disease severity.
Detailed description
Osteopetrosis is a rare inherited metabolic bone disease characterized by impaired osteoclast function resulting in defective bone resorption and generalized high bone mass and mineral density (BMD). In patients with severe disease, this high bone mass compromises bone marrow space leading to marrow failure and frequent infections, along with hepatosplenomegaly from extramedullary hematopoiesis. Currently, the only treatment for individuals with severe forms of osteopetrosis is hematopoietic cell transplantation (HCT), however survival in patients with osteopetrosis treated with HCT is only around 55%. Therefore, this treatment is only indicated in select individuals with life-threatening complications of their disease. Thus additional treatments for osteopetrosis are needed both for individuals who are not candidates for HCT and to prolong the time until HCT is needed.
Interferon gamma (IFN-γ) is a naturally occurring cytokine that has been shown to have anti-microbial and anti-viral immunomodulatory effects, and is a potent stimulator of superoxide anion production which in turn promotes the formation and activation of osteoclasts. Two previous studies of IFN-γ1b in a small group of individuals with osteopetrosis found a decrease in trabecular bone area, an increase in marrow space, a decrease in the number of severe infections requiring antibiotic therapy, and an increase in superoxide generation by granulocyte-macrophage colonies.
Therefore, the investigators will conduct an early phase 2, multi-center, open-label, 12-month clinical trial of ACTIMMUNE (IFN-γ1b) treatment of patients with intermediate osteopetrosis to determine the following:
- The feasibility and tolerability of interferon gamma-1b treatment for 1 year in patients with intermediate osteopetrosis. Specifically, i) the ability to enroll patients, and ii) continued treatment throughout the 1-year observational period.
- Change in immunologic and hematologic function, bone mineral density and osteoclast function, physical function and quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| gamma interferon-1b | Experimental | Drug: Interferon gamma-1bGamma interferon-1b 100 mcg subcutaneous (SC) 3 times weekly for 12 months |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Diagnosis of osteopetrosis; and
- Anemia (Hemoglobin <12 g/dL) not related to iron deficiency, or
- Neutropenia (Neutrophil count <1000 neutrophils/ul unsupported with cytokines), or
- Thrombocytopenia (Platelet count <50,000 cells x 109/L), or
- History of impaired bone healing, or
Key exclusion criteria (6 listed)
- 12 months or fewer following HCT;
- Pregnancy or breastfeeding;
- Known or suspected allergy to interferon gamma-1b or related products;
- Participation in simultaneous therapeutic study that involves an investigational study drug or agent within 4 weeks of study enrollment;
- ALT greater than 3 fold higher than normal; or
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 |
|---|---|---|
| Interferon gamma-1bAlso: ACTIMMUNEgamma interferon-1b dose escalation over first 4 weeks of study to 100 mcg SC 3 times weekly | Drug | gamma interferon-1b |
Primary outcome
Number of Participants With Treatment Related Adverse Events CTCAE v4.0 Grade 3 or Higher
Time frame: 12 months
Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 defines a Grade 4 event as having life-threatening consequences, and/or urgent intervention indicated.
3 secondary outcomes
Percent Change From Baseline in Bone Mineral Density (BMD)
Time frame: 6 months
Change From Baseline in White Blood Cell Count (WBC)
Time frame: 6 months
Change From Baseline in Pain
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34056870Lertwilaiwittaya P, Suktitipat B, Khongthon P, Pongsapich W, Limwongse C, Pithukpakorn M. Identification of novel mutation in RANKL by whole-exome sequencing in a Thai family with osteopetrosis; a case report and review of RANKL osteopetrosis. Mol Genet Genomic Med. 2021 Jul;9(7):e1727. doi: 10.1002/mgg3.1727. Epub 2021 May 30.
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Active, not recruitingPhase 2
MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
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RecruitingPhase 2
Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT
Primary Immunodeficiency (PID), Congenital Bone Marrow Failure Syndromes
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.
Lynda E Polgreen, MD, MS principal investigator
Los Angeles BioMedical Research Center at Harbor-UCLA
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Interferon gamma-1b in people with Osteopetrosis, run by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center at 2 sites 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 9 inclusion and 6 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 22 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 11 Oct 2023). 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?
Number of Participants With Treatment Related Adverse Events CTCAE v4.0 Grade 3 or Higher (time frame: 12 months). 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 NCT02666768, 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 22 Oct 2024.