Osteogenesis ImperfectaPhase 1NCT03064074
Safety of Fresolimumab in the Treatment of Osteogenesis Imperfecta
A Phase 1 study testing Fresolimumab in people with Osteogenesis Imperfecta, run by Baylor College of Medicine at 2 sites in United States.
Trial summary
Osteogenesis Imperfecta (OI) is a rare disorder that causes bones to break easily. People with OI may have broken bones with little or no trauma, dentinogenesis imperfecta (DI), and, in adult years, hearing loss. OI can range from very severe to very mild. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Osteogenesis Imperfecta
- What is being tested?
- Fresolimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 2 sitesUnited States
- Study dates
- 15 Nov 2017to 4 Jul 2022
- Phase
- Phase 1
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide signed informed consent.
- Are 18 years or older
- Have a diagnosis of moderate-to-severe OI based on various clinical features
- Have genetic mutations that include glycine substitution in COL1A1 or COL1A2, or pathogenic variants in CRTAP, PPIB, or LEPRE1 (if genetic information is unavailable at screening, this may be assessed at screening visit on a clinical or research basis).
- Females of child-bearing potential must have a negative urine pregnancy test, agree to and have the ability to use acceptable birth control method for entire duration of the study.
- For Males enrolled in the study, partners must agree to use an acceptable form of birth control for the entire duration of the study.
Who cannot join
- Fracture less than 3 months prior to the screening visit.
- Rodding or instruments that prevents reliable bone mineral density (BMD) assessment.
- Have a known unhealed fracture involving a long bone.
- Do not meet laboratory safety requirements such as: Vitamin D < 15 ng/dL Serum albumin-corrected calcium levels below 8 mg/dL, Hemoglobin < 10 g/dL, Platelet count < 75,000mm3;, Prothrombin time/(PT/INR) international normalized ratio > 1.5 times Upper Limit of Normal (ULN), Clinical or laboratory abnormality of Grade III or higher as assessed by CTCAE v4.0 which in the view of investigator would compromise safety.
- Have an EKG with QTc of > 450 ms
- Have a known allergy to fresolimumab.
Show all 19Show fewer
- Have current clinically significant infection.
- Have a personal history of basal cell carcinoma, squamous cell carcinoma or keratoacanthomas, a personal history of cancer, recent or remote.
- Have evidence of untreated cavities or planned invasive dental work during the study period.
- Have had organ transplantation.
- Have known or suspected valvular heart disease.
- Plan to have skeletal surgery in the study period.
- Have had osteotomy 5 months prior to the screening visit.
- Being treated with zoledronic acid or pamidronate less than 12 months of screening OR oral bisphosphonates less than 6 months of screening OR teriparatide less than one year of screening.
- Being treated with systemic glucocorticoids
- Have autoimmune diseases being treated with glucocorticoids or other biologic agents.
- Enrolled in another clinical trial and receiving treatment with another investigational agent
- Pregnant or planning to get pregnant during the study period.
- Nursing mothers.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Baylor College of Medicine
Houston, Texas, 77030
Oregon Health Science University
Portland, Oregon, 97239
About this study
Official title: Multicenter Study to Evaluate Safety of Fresolimumab in Adults With Moderate-to-severe Osteogenesis Imperfecta
Osteogenesis Imperfecta (OI) is a rare disorder that causes bones to break easily. People with OI may have broken bones with little or no trauma, dentinogenesis imperfecta (DI), and, in adult years, hearing loss. OI can range from very severe to very mild. The current standard-of-care for severe types of OI involves the use of IV medications (bisphosphonates) and surgery to put rods in bones to strengthen them. These therapies, although often life-saving, are new and very little is known about their long-term effects on bone and other body systems.
Transforming growth factor beta (TGF-β) is a protein important in bone formation. Fresolimumab is an antibody that can silence TGF-β . In studies with mice with OI, it has been shown that silencing TGF-β can lead to higher bone mass, quality and strength. The purpose of this study is to determine if fresolimumab is safe in the treatment of OI.
Read the detailed description
Osteogenesis Imperfecta (OI) is a rare disorder that causes bones to break easily. People with OI may have broken bones with little or no trauma, dentinogenesis imperfecta (DI), and, in adult years, hearing loss. It is seen in both genders and all races. OI can range from very severe to very mild. Individuals with the most severe type of OI may die at birth. People with severe OI who survive may have bowed arms and legs, very short stature and be unable to walk. People with the mildest form of OI may only break bones occasionally and have normal height and lifespan. Breaks can occur in any bone, but are most common in the arms and legs. The current standard-of-care for severe types of OI involves the use of IV medications (bisphosphonates) and surgery to put rods in bones to strengthen them. These therapies, although often life-saving, are new and very little is known about their long-term effects on bone and other body systems.
TGF-β is a protein important in bone formation. Studies have shown that increased TGF-β activity leads to lower bone mass and strength and increased fractures. Fresolimumab is an antibody that can silence TGF-β . In studies with mice with OI, it has been shown that silencing TGF-β can lead to higher bone mass, quality and strength.
- Conditions
- Osteogenesis Imperfecta
- Being tested
- Fresolimumab
- Medical subject headings
- Osteogenesis Imperfecta
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FresolimumabDrug
The purpose of this study is to determine if fresolimumab is safe as a treatment for OI. We will evaluate the safety of a single dose of fresolimumab in the 1st stage of the study. We will evaluate the safety of multiple doses of fresolimumab in the 2nd stage of the study. The Investigators will evaluate the effect of the two doses of fresolimumab in Stage 1 on markers of bone turnover and determine the dose that shows the greatest reduction in bone turnover markers compared to no treatment. This dose will be chosen for the repeat dose studies. If there were no significant changes between the bone turnover markers with either dose, the 4 mg/kg dose will be chosen for the repeat dose study.
| Study group | Role | What they receive |
|---|---|---|
| Stage 1 Low dose | Experimental | There are a total of 6 study visits within approximately a 6 month timespan. Investigators will evaluate the safety of a single administration of fresolimumab in adult patients with OI. Subjects will receive a single-dose of 1 mg/kg of fresolimumab (n=4).
At each study visit, the participant may have the following testing done:
* Physical exam
* Vitals
* Blood draw for safety labs, pharmacokinetics, etc
* If the participant is female, she will have a pregnancy test
* EKG
* DXA
* Infusion of the study drug Receives: Drug: Fresolimumab |
| Stage 2 High dose | Experimental | There are a total of 6 study visits within approximately a 6 month timespan. Investigators will evaluate the safety of a single administration of fresolimumab in adult patients with OI. Subjects will receive a single-dose of 4 mg/kg of fresolimumab (n=4).
At each study visit, the participant may have the following testing done:
* Physical exam
* Vitals
* Blood draw for safety labs, pharmacokinetics, etc
* If the participant is female, she will have a pregnancy test
* EKG
* DXA
* Infusion of the study drug Receives: Drug: Fresolimumab |
| Stage 2 Repeat dose every 6 months | Experimental | Fresolimumab will be administered every six months for a total treatment period of 12 months (Total Anticipated n=4). The dose to be administered (1 or 4 mg/kg) will be chosen after completion of Stage 1. The primary Stage 2 endpoint will be safety measures assessed over 12 months. The secondary endpoints will be changes in markers of bone remodeling, bone mineral density, estimated strength.
At each study visit, participants may have the following testing done:
* Physical exam
* Vitals
* Blood draw for safety labs, pharmacokinetics, etc
* If the participant is female, she will have a pregnancy test
* EKG
* DXA
* Infusion of the study drug
* Skeletal survey
* Peripheral quantitative CT (pQCT) of the forearm
* Quality of Life Surveys
* Pulmonary function test
* Walk test Receives: Drug: Fresolimumab |
| Stage 2 Repeat doses every 3 months | Experimental | Fresolimumab will be administered every three months for a total treatment period of 12 months (Total anticipated n=4). The dose to be administered (1 or 4 mg/kg) will be chosen after completion of Stage 1. The primary Stage 2 endpoint will be safety measures assessed over 12 months. The secondary endpoints will be changes in markers of bone remodeling, bone mineral density, estimated strength.
At each study visit, participants may have the following testing done:
* Physical exam
* Vitals
* Blood draw for safety labs, pharmacokinetics, etc
* If the participant is female, she will have a pregnancy test
* EKG
* DXA
* Infusion of the study drug
* Skeletal survey
* Peripheral quantitative CT (pQCT) of the forearm
* Quality of Life Surveys
* Pulmonary function test
* Walk test Receives: Drug: Fresolimumab |
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 as Assessed by CTCAE v4.0
Safety of single and repeat doses of fresolimumab will be assessed in adult patients with moderate to severe osteogenesis imperfecta
Measured: 6 months for single dose study and 12 months for repeat dose study
Secondary outcomes (1)
Percentage Change in Bone Turnover Markers or P1NP, Osteocalcin or Ocn, and C-terminal Telopeptide or CTX
Percentage change in bone turnover markers from baseline to Day 180
Measured: 6 months in single dose study and 12 months in repeat dose study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2017
- Study start15 Nov 2017
- Primary completion4 Jul 2022
- Study completion4 Jul 2022
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 Osteogenesis ImperfectaStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme, a Sanofi Company, Oregon Health and Science University
- Responsible party
- Principal investigator, Brendan Lee, Baylor College of Medicine
- Investigators
- Sandesh Nagamani, M.D., Study chair, Baylor College of MedicineVReid Sutton, M.D., Study chair, Baylor College of MedicineBrendan Lee, M.D., Ph.D., Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03064074
- Sponsor's protocol ID
- H37912
- Status last verified
- Dec 2024
- First submitted
- 13 Oct 2016
- Last updated
- 4 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Song IW, Nagamani SC, Nguyen D, Grafe I, Sutton VR, Gannon FH, Munivez E, Jiang MM, Tran A, Wallace M, Esposito P, Musaad S, Strudthoff E, McGuire S, Thornton M, Shenava V, Rosenfeld S, Huang S, Shypailo R, Orwoll E, Lee B. Targeting TGF-beta for treatment of osteogenesis imperfecta. J Clin Invest. 2022 Apr 1;132(7):e152571. doi: 10.1172/JCI152571.
PubMed 35113812
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Study to Evaluate Safety of Fresolimumab in Adults With Moderate-to-severe Osteogenesis Imperfecta
- ClinicalTrials.gov ID
- NCT03064074
- Acronym / sponsor ID
- H37912
- Conditions
- Osteogenesis Imperfecta
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- Genzyme, a Sanofi Company, Oregon Health and Science University
- Study start
- 15 Nov 2017 (actual)
- Primary completion
- 4 Jul 2022 (actual)
- Study completion
- 4 Jul 2022 (actual)
- First posted
- 24 Feb 2017 (actual)
- Results
- Posted 8 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Osteogenesis Imperfecta (OI) is a rare disorder that causes bones to break easily. People with OI may have broken bones with little or no trauma, dentinogenesis imperfecta (DI), and, in adult years, hearing loss. OI can range from very severe to very mild. The current standard-of-care for severe types of OI involves the use of IV medications (bisphosphonates) and surgery to put rods in bones to strengthen them. These therapies, although often life-saving, are new and very little is known about their long-term effects on bone and other body systems.
Transforming growth factor beta (TGF-β) is a protein important in bone formation. Fresolimumab is an antibody that can silence TGF-β . In studies with mice with OI, it has been shown that silencing TGF-β can lead to higher bone mass, quality and strength. The purpose of this study is to determine if fresolimumab is safe in the treatment of OI.
Detailed description
Osteogenesis Imperfecta (OI) is a rare disorder that causes bones to break easily. People with OI may have broken bones with little or no trauma, dentinogenesis imperfecta (DI), and, in adult years, hearing loss. It is seen in both genders and all races. OI can range from very severe to very mild. Individuals with the most severe type of OI may die at birth. People with severe OI who survive may have bowed arms and legs, very short stature and be unable to walk. People with the mildest form of OI may only break bones occasionally and have normal height and lifespan. Breaks can occur in any bone, but are most common in the arms and legs. The current standard-of-care for severe types of OI involves the use of IV medications (bisphosphonates) and surgery to put rods in bones to strengthen them. These therapies, although often life-saving, are new and very little is known about their long-term effects on bone and other body systems.
TGF-β is a protein important in bone formation. Studies have shown that increased TGF-β activity leads to lower bone mass and strength and increased fractures. Fresolimumab is an antibody that can silence TGF-β . In studies with mice with OI, it has been shown that silencing TGF-β can lead to higher bone mass, quality and strength.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Stage 1 Low dose | Experimental | Drug: FresolimumabThere are a total of 6 study visits within approximately a 6 month timespan. Investigators will evaluate the safety of a single administration of fresolimumab in adult patients with OI. Subjects will receive a single-dose of 1 mg/kg of fresolimumab (n=4). At each study visit, the participant may have the following testing done: * Physical exam * Vitals * Blood draw for safety labs, pharmacokinetics, etc * If the participant is female, she will have a pregnancy test * EKG * DXA * Infusion of the study drug |
| Stage 2 High dose | Experimental | Drug: FresolimumabThere are a total of 6 study visits within approximately a 6 month timespan. Investigators will evaluate the safety of a single administration of fresolimumab in adult patients with OI. Subjects will receive a single-dose of 4 mg/kg of fresolimumab (n=4). At each study visit, the participant may have the following testing done: * Physical exam * Vitals * Blood draw for safety labs, pharmacokinetics, etc * If the participant is female, she will have a pregnancy test * EKG * DXA * Infusion of the study drug |
| Stage 2 Repeat dose every 6 months | Experimental | Drug: FresolimumabFresolimumab will be administered every six months for a total treatment period of 12 months (Total Anticipated n=4). The dose to be administered (1 or 4 mg/kg) will be chosen after completion of Stage 1. The primary Stage 2 endpoint will be safety measures assessed over 12 months. The secondary endpoints will be changes in markers of bone remodeling, bone mineral density, estimated strength. At each study visit, participants may have the following testing done: * Physical exam * Vitals * Blood draw for safety labs, pharmacokinetics, etc * If the participant is female, she will have a pregnancy test * EKG * DXA * Infusion of the study drug * Skeletal survey * Peripheral quantitative CT (pQCT) of the forearm * Quality of Life Surveys * Pulmonary function test * Walk test |
| Stage 2 Repeat doses every 3 months | Experimental | Drug: FresolimumabFresolimumab will be administered every three months for a total treatment period of 12 months (Total anticipated n=4). The dose to be administered (1 or 4 mg/kg) will be chosen after completion of Stage 1. The primary Stage 2 endpoint will be safety measures assessed over 12 months. The secondary endpoints will be changes in markers of bone remodeling, bone mineral density, estimated strength. At each study visit, participants may have the following testing done: * Physical exam * Vitals * Blood draw for safety labs, pharmacokinetics, etc * If the participant is female, she will have a pregnancy test * EKG * DXA * Infusion of the study drug * Skeletal survey * Peripheral quantitative CT (pQCT) of the forearm * Quality of Life Surveys * Pulmonary function test * Walk test |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Willing and able to provide signed informed consent.
- Are 18 years or older
- Have a diagnosis of moderate-to-severe OI based on various clinical features
- Have genetic mutations that include glycine substitution in COL1A1 or COL1A2, or pathogenic variants in CRTAP, PPIB, or LEPRE1 (if genetic information is unavailable at screening, this may be assessed at screening visit on a clinical or research basis).
- Females of child-bearing potential must have a negative urine pregnancy test, agree to and have the ability to use acceptable birth control method for entire duration of the study.
Key exclusion criteria (19 listed)
- Fracture less than 3 months prior to the screening visit.
- Rodding or instruments that prevents reliable bone mineral density (BMD) assessment.
- Have a known unhealed fracture involving a long bone.
- Do not meet laboratory safety requirements such as: Vitamin D < 15 ng/dL Serum albumin-corrected calcium levels below 8 mg/dL, Hemoglobin < 10 g/dL, Platelet count < 75,000mm3;, Prothrombin time/(PT/INR) international normalized ratio > 1.5 times Upper Limit of Normal (ULN), Clinical or laboratory abnormality of Grade III or higher as assessed by CTCAE v4.0 which in the view of investigator would compromise safety.
- Have an EKG with QTc of > 450 ms
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 |
|---|---|---|
| FresolimumabThe purpose of this study is to determine if fresolimumab is safe as a treatment for OI. We will evaluate the safety of a single dose of fresolimumab in the 1st stage of the study. We will evaluate the safety of multiple doses of fresolimumab in the 2nd stage of the study. The Investigators will evaluate the effect of the two doses of fresolimumab in Stage 1 on markers of bone turnover and determine the dose that shows the greatest reduction in bone turnover markers compared to no treatment. This dose will be chosen for the repeat dose studies. If there were no significant changes between the bone turnover markers with either dose, the 4 mg/kg dose will be chosen for the repeat dose study. | Drug | Stage 1 Low dose, Stage 2 High dose, Stage 2 Repeat dose every 6 months, Stage 2 Repeat doses every 3 months |
Primary outcome
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Time frame: 6 months for single dose study and 12 months for repeat dose study
Safety of single and repeat doses of fresolimumab will be assessed in adult patients with moderate to severe osteogenesis imperfecta
1 secondary outcome
Percentage Change in Bone Turnover Markers or P1NP, Osteocalcin or Ocn, and C-terminal Telopeptide or CTX
Time frame: 6 months in single dose study and 12 months in repeat dose study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35113812Song IW, Nagamani SC, Nguyen D, Grafe I, Sutton VR, Gannon FH, Munivez E, Jiang MM, Tran A, Wallace M, Esposito P, Musaad S, Strudthoff E, McGuire S, Thornton M, Shenava V, Rosenfeld S, Huang S, Shypailo R, Orwoll E, Lee B. Targeting TGF-beta for treatment of osteogenesis imperfecta. J Clin Invest. 2022 Apr 1;132(7):e152571. doi: 10.1172/JCI152571.
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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.
Sandesh Nagamani, M.D. study chair
Baylor College of Medicine
VReid Sutton, M.D. study chair
Baylor College of Medicine
Brendan Lee, M.D., Ph.D. principal investigator
Baylor College of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fresolimumab in people with Osteogenesis Imperfecta, run by Baylor College of Medicine 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 6 inclusion and 19 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 4 Dec 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Oct 2024). 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 as Assessed by CTCAE v4.0 (time frame: 6 months for single dose study and 12 months for repeat dose study). 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 NCT03064074, 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 4 Dec 2024.