Extension of Study 20130173 in Children and Young Adults with OI
Research type
Research Study
Full title
Multicenter, Single-arm Open-label Extension Study to Assess Long-term Safety and Efficacy of Current or Prior Treatment with Denosumab in Children/Young Adults with Osteogenesis Imperfecta
IRAS ID
248188
Contact name
Nicholas Bishop
Contact email
Sponsor organisation
Amgen
Eudract number
2018-000550-21
Duration of Study in the UK
5 years, 0 months, 28 days
Research summary
Research Summary
The purpose of this study is to see if denosumab has an effect on the amount of minerals (such as calcium) in the bones to improve bone mass and whether it causes any side effects. Osteogenesis imperfecta (OI) is an inherited skeletal disorder identified by increased bone fragility and low bone mass (low calcium in the bone). Osteogenesis imperfecta is one of the most common types of osteoporosis (bone disorder) in children. Currently, there are no approved medicinal products for the treatment of osteogenesis imperfecta, except for neridronate, which is only approved for the treatment of OI in Italy. This study is an extension study to understand the long-term safety and effectiveness of denosumab in children/young adults with OI, who have either had previous treatment or current treatment of denosumab. Denosumab is approved for use in people with osteoporosis at high risk of fracture but not with people that have OI. A total of about 150 participants are expected to take part in this study. This study will take place in approximately 40 centres in Canada, US, Australia, Bulgaria, Czech Republic, Germany, Hungary, Poland, Belgium, UK, France, Italy, Spain. Participants will be in this study for about 24months, with up to 10 visits taking place approximately once every 3 months or once every 6 months depending on participant’s treatment (denosumab (6 monthly injection), alternative osteoporosis medication, or observation only). During the study, participants will undergo a number of procedures and assessments, including physical examination, blood tests, reviews of adverse event, DXA scans(DXA = Dual-energy X-ray absorptiometry) and other X-ray assessments.
Summary of Results
1. Study Name Title of the Study:
Multicenter, Single-arm Open-label Extension Study to Assess Long-term Safety and Efficacy of Current or Prior Treatment With Denosumab in Children/Young Adults With Osteogenesis Imperfecta Brief Title:
Open-label Extension of Study 20130173 of Denosumab in Children and Young Adults with Osteogenesis Imperfecta Protocol Number:
20170534
EU Trial Number:
2018-000550-21
Other Identifiers:
NCT03638128
Date of This Summary:
08 September 2022
What does this summary cover?
This summary shows the main results from one clinical study. The results are only for this study. Other studies may find different results. Researchers and health authorities look at the results of many studies to decide which medicines work best and are safest for patients.
Amgen has committed to make research results available to the public. This summary has been provided as part of that commitment and should not be used for any other purpose. It should not be considered to make a claim for any product or to guide treatment decisions.
Some information in this summary may be different from the approved labelling for denosumab. Your healthcare professional should refer to the full prescribing information for proper use of denosumab.2. Who Sponsored This Study?
Amgen Inc. One Amgen Center Drive Thousand Oaks, CA 91320-1799 USA Phone (United Kingdom): +44 1223 436441 Amgen Inc. is the sponsor of the study who made denosumab, the medicine tested in the study. Amgen would like to thank everyone who participated in this study and feels it is important to share the results of this study.3. General Information About the Clinical Study Where and when was the study done?
• This study took place in Belgium, Canada, Czech Republic, France, Germany, Hungary, Italy, Poland, Spain, United Kingdom, and United States.
• The study began in July 2018 and ended in March 2022.
• The study was stopped earlier than planned due to safety concerns about high levels of calcium in the participants’ bones.
Why was the study done?
Osteogenesis imperfecta (OI) is an inherited disorder that affects the development of bones. People with OI may have bones that break very easily. OI is also known as “brittle bone disease”.
Denosumab is a medicine that was being studied as a possible treatment for OI. Denosumab is approved for use in adults with a different bone disease, but it has not been approved for use in children or for the treatment of OI.
This was a phase 3 study, the late stage of the development process of medicines for humans. This was an extension study for participants from a previous study with denosumab. The main purpose of this study was to find out more about the safety of denosumab in children and young adults with OI, when used long-term.4. Who Was Included in This Study?
A total of 75 participants joined this study. 27 participants were treated with at least one dose of denosumab 1 mg/kg every 3 months. 27 other participants were treated with at least one dose of denosumab 1 mg/kg every 6 months (these participants did not receive denosumab 1 mg/kg every 3 months). Of these 27 participants, 14 participants (52%, or about 52 out of 100) were boys/young men and 13 participants (48%, or about 48 out of 100) were girls/young women. They ranged in age from 6 to 26 years, with an average age of about 13 to 14 years.
This study took place at 20 study centers across Belgium, Canada, Czech Republic, France, Germany, Hungary, Italy, Poland, Spain, United Kingdom, and United States. The numbers of participants in each country are listed below.
• Belgium: 3 participants
• Canada: 10 participants
• Czech Republic: 2 participants
• France: 2 participants
• Germany: 29 participants
• Hungary: 4 participants
• Italy: 6 participants
• Poland: 1 participant
• Spain: 3 participants
• United Kingdom: 8 participants
• United States: 7 participants
Children and young adults who had been diagnosed with OI and had participated in a previous study (Study 20130173) with denosumab could join this study.5. Which Medicines Were Studied?
A total of 75 children and young adults who had participated in Study 20130173 joined this study, and 54 of these children were treated with denosumab during this study. The study was planned to last a total of 96 weeks. Participants could receive
1 of the following treatment regimens, as determined to be appropriate by the study doctor:
• Denosumab 1 milligram per kilogram of body weight (mg/kg), up to a maximum dose of 60 mg, given as an injection under the skin, given either every 3 months or every 6 months for a total of 84 weeks. These participants also received daily calcium and vitamin D supplements • Standard OI treatment as typically prescribed in the participant’s country (which may have also included calcium and vitamin D supplements) • Observation only (no OI medication) This was an open-label study, which means that the researchers, study doctors, participants, and their parents/guardians knew which treatments the participants received during the study.
This study was stopped earlier than planned due to safety concerns about high levels of calcium in the children’s blood. All children immediately stopped receiving denosumab. The researchers monitored the children for any medical problems or other safety concerns for 6 months after their last dose of denosumab.6. What Were the Side Effects?
All medicines can cause side effects, or unwanted medical problems that may happen when you take a medicine. In this study, doctors reported all the medical problems participants had. Doctors believed some of the problems could have been caused by the study medicine(s). These possible side effects are listed below.
The table below shows how many participants had side effects. Side Effects During the Study Denosumab 1 mg/kg Every 6 Months (27 participants) Denosumab 1 mg/kg Every 3 Months (27 participants) How many participants had serious side effects?
1 participant (4%)
3 participants (11%) How many participants had non-serious side effects? 17 participants (63%) 6 participants (22%) How many participants died from side effects?
0 participants (0%)
0 participants (0%) How many participants stopped taking the study medicine because of side effects? 1 participant (4%) 0 participants (0%) If a participant had to stay in the hospital or died because of a side effect, the doctor reported that the side effect was serious. No participant died due to a side effect.
The table below shows the serious side effects. Serious Side Effects During the Study Serious side effect Denosumab 1 mg/kg Every 6 Months (27 participants) Denosumab 1 mg/kg Every 3 Months (27 participants) High level of calcium in blood
0 participants (0%)
3 participants (11%) Kidney stones 1 participant (4%) 0 participants (0%) The table below shows the non-serious side effects that occurred in at least 10% of participants (or about 10 out of 100).
Non-serious Side Effects During the Study Non-serious side effect Denosumab 1 mg/kg Every 6 Months (27 participants) Denosumab 1 mg/kg Every 3 Months (27 participants) High level of calcium in urine
15 participants (56%)
1 participant (4%) Pain in arm or leg 4 participants (15%) 0 participants (0%) This section only shows the most often reported side effects considered by the study doctor as related to study medicine. No single clinical study can give a complete picture of the benefits and risks of a medicine.
More results may be available at the websites listed at the end of this summary.7. How Has This Study Helped Participants and Researchers?
What else is important to know about these results?
These results are only for this clinical study, which looked at a sample of 75 children and young adults with OI. Not all participants in the study had the same results. The results for any single participant could have been better or worse than the results for their group. Other studies may find different results. These results do not explain how a study medicine may work in a single person. Many studies are needed to show the benefits and risks of a medicine that is still being tested. This research may help future participants and families by helping doctors understand more about denosumab.
8. Are There Plans for Further Studies?
If more clinical studies are done, they may be listed on public websites, such as those below. Search for study medicine name denosumab on the websites below.9. Where Can I Find More Information About This Study?
To find out more about this study, check these websites:
• EU Clinical Trials Information System https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7C5069177adb8547cf0c1a08daf87f0978%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638095521746708531%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=yWQiF53MRWXfzHSIk%2FTq3AwikgQYurczwNHT1DPiwmE%3D&reserved=0. Use the study identifier 2018-000550-21 • https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7C5069177adb8547cf0c1a08daf87f0978%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638095521746708531%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=Hmyml5J4CTznWOgHLdBVFZSyrPLYivWXzsb08lkb7eQ%3D&reserved=0. Use the study identifier NCT03638128 If you or your child participated in the study and have questions about the study results, the doctor or staff at your study center may be able to answer them.REC name
North East - Newcastle & North Tyneside 2 Research Ethics Committee
REC reference
18/NE/0282
Date of REC Opinion
7 Mar 2019
REC opinion
Further Information Favourable Opinion