A Phase 1 interventional study of Fresolimumab in Osteogenesis Imperfecta, sponsored by Baylor College of Medicine. Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-12-04.
Sponsored by Baylor College of Medicine · Phase 1, Interventional, and Treatment
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.
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.
84 studies on the registry are indexed under Osteogenesis Imperfecta; 20 are open to participants now.
This study's enrollment of 11 is below the median of 28 across 60 interventional studies indexed under Osteogenesis Imperfecta.
Browse Osteogenesis Imperfecta studies →Baylor College of Medicine is the lead sponsor of 747 studies on the registry; 110 are open to participants now.
Of its 84 completed or terminated interventional studies of FDA-regulated products, 45 (54%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
Drug: Fresolimumab
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
Drug: Fresolimumab
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
Drug: Fresolimumab
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
Drug: Fresolimumab
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.
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
Time frame: 6 months for single dose study and 12 months for repeat dose study
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
Time frame: 6 months in single dose study and 12 months in repeat dose study
| Milestone | Stage 1 Low Dose | Stage 2 High Dose | Stage 2 Repeat Dose Every 6 Months | Stage 2 Repeat Doses Every 3 Months |
|---|---|---|---|---|
| Started | 4 | 4 | 2 | 1 |
| Completed | 4 | 4 | 2 | 0 |
| Not completed | 0 | 0 | 0 | 1 |
| Withdrew: Physician decision | 0 | 0 | 0 | 1 |
Safety of single and repeat doses of fresolimumab will be assessed in adult patients with moderate to severe osteogenesis imperfecta
| Participants | Stage 1 Low Dose | Stage 2 High Dose | Stage 2 Repeat Dose Every 6 Months | Stage 2 Repeat Doses Every 3 Months |
|---|---|---|---|---|
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | 2 | 4 | 2 | 1 |
Percentage change in bone turnover markers from baseline to Day 180
| Percent change | Stage 1 Low Dose | Stage 2 High Dose | Stage 2 Repeat Dose Every 6 Months | Stage 2 Repeat Doses Every 3 Months |
|---|---|---|---|---|
| Percentage Change in P1NP | 28.31 ± 17.44 | 24.95 ± 17.44 | 118.63 ± 45.40 | NA ± NA |
| Percentage Change in CTX | 49.89 ± 29.29 | -4.02 ± 33.82 | 51.83 ± 34.56 | NA ± NA |
| Percentage change in Osteocalcin | 76.4 ± 39.1 | -18.6 ± 39.13 | 83.9 ± 17.56 | NA ± NA |
Collected over 6 Months for single dose study and 1 year for the multi dose study. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Stage 1 Low Dose | 0/4 (0%) | 0/4 (0%) | 4/4 (100%) |
| Stage 2 High Dose | 0/4 (0%) | 0/4 (0%) | 4/4 (100%) |
| Stage 2 Repeat Dose Every 6 Months | 0/2 (0%) | 1/2 (50%) | 2/2 (100%) |
| Stage 2 Repeat Doses Every 3 Months | 0/1 (0%) | 1/1 (100%) | 1/1 (100%) |
| Event | Stage 1 Low Dose | Stage 2 High Dose | Stage 2 Repeat Dose Every 6 Months | Stage 2 Repeat Doses Every 3 Months |
|---|---|---|---|---|
| FractureMusculoskeletal and connective tissue disorders | 0/4 | 0/4 | 1/2 | 1/1 |
| Event | Stage 1 Low Dose | Stage 2 High Dose | Stage 2 Repeat Dose Every 6 Months | Stage 2 Repeat Doses Every 3 Months |
|---|---|---|---|---|
| General Adverse eventsInvestigations | 4/4 | 4/4 | 2/2 | 1/1 |
| Age, Categorical(Participants) | Stage 1 Low Dose | Stage 2 High Dose | Stage 2 Repeat Dose Every 6 Months | Stage 2 Repeat Doses Every 3 Months | Total |
|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 4 | 4 | 2 | 1 | 11 |
| >=65 years | 0 | 0 | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Stage 1 Low Dose | Stage 2 High Dose | Stage 2 Repeat Dose Every 6 Months | Stage 2 Repeat Doses Every 3 Months | Total |
|---|---|---|---|---|---|
| Female | 2 | 3 | 1 | 1 | 7 |
| Male | 2 | 1 | 1 | 0 | 4 |
| Race (NIH/OMB)(Participants) | Stage 1 Low Dose | Stage 2 High Dose | Stage 2 Repeat Dose Every 6 Months | Stage 2 Repeat Doses Every 3 Months | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 1 | 0 | 0 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 | 0 |
| White | 3 | 2 | 2 | 1 | 8 |
| More than one race | 1 | 1 | 0 | 0 | 2 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | Stage 1 Low Dose | Stage 2 High Dose | Stage 2 Repeat Dose Every 6 Months | Stage 2 Repeat Doses Every 3 Months | Total |
|---|---|---|---|---|---|
| United States | 4 | 4 | 2 | 1 | 11 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Nov 2017 to primary completion in Jul 2022, 55 months.
Results were first posted in Oct 2024, 2 years 3 months after primary completion.
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Studies of the drug tested here: Fresolimumab