Repurposing carbamazepine for treatment of skeletal dysplasia in childre
- Conditions
- Skeletal dysplasiaMusculoskeletal Diseases
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 27
Current inclusion criteria as of 16/05/2024:
1. Participants where a pathogenic mutation in the gene encoding the COL10A1 protein has been identified by sequence analysis
2. Ambulant at the time of consent/assent, with open epiphyses
3. Willing and able to attend for safety monitoring assessments
4. Willing and able to adhere to the trial visit schedule and other protocol requirements
5. Capable of giving informed consent, or if appropriate, participants having an acceptable individual capable of giving consent on the participant’s behalf (e.g. parent or legal guardian of a child under 16 years of age)
6. Written informed consent signed (by parent(s)/legal guardian and/or the subject, according to the local regulations)
7. If female and of childbearing potential, the participant must have a negative pregnancy test [urine beta-human chorionic gonadotropin (ß-hCG)] at baseline and agree to regular pregnancy testing during the trial
8. Sexually active female participants of childbearing potential must practice true abstinence in line with their preferred and usual lifestyle, or use two acceptable effective methods of contraception whilst on treatment and for a period of 28 days after discontinuation: a barrier method such as a condom or occlusive cap (diaphragm or cervical/vault cap) with spermicidal foam/gel/film/cream/suppository and an established non-barrier method such as oral, injected, or implanted hormonal methods (hormonal preparations must contain not less than 50µg oestrogen). Use of some alternative non-hormonal method of contraception should be considered: an intrauterine device or intrauterine system for the entire duration of the treatment period and for a period of 28 days after discontinuation.
Previous inclusion criteria:
1. Pathogenic mutation in the gene encoding the COL10A1 protein has been identified by sequence analysis
2. Ambulant at the time of consent/assent, with open epiphyses
3. Willing to attend for safety monitoring assessments
4. Willing and able to adhere to the trial visit schedule and other protocol requirements
5. Capable of giving informed consent, or if appropriate, participants having an acceptable individual capable of giving consent on the participant’s behalf (e.g. parent or legal guardian of a child under 16 years of age)
6. Written informed consent signed (by parent(s)/legal guardian and/or the subject, according to the local regulations)
7. The patient, if female and of childbearing potential, must have a negative pregnancy test [urine beta-human chorionic gonadotropin (ß-hCG)] at baseline and agree to regular pregnancy testing during the trial
8. Sexually active female patients of childbearing potential are required to practice true abstinence in line with their preferred and usual lifestyle or use two acceptable effective methods of contraception, a barrier method such as a condom or occlusive cap (diaphragm or cervical/vault cap) with spermicidal foam/gel/film/cream/suppository and an established non-barrier method such as oral, injected, or implanted hormonal methods (hormonal preparations must contain not less than 50 µg oestrogen) use of some alternative non-hormonal method of contraception should be considered, an intrauterine device or intrauterine system for the entire duration of the treatment period
Current exclusion criteria as of 16/05/2024:
1. Patients who have reached skeletal maturity*
2. Patients who have a planned surgery or planned osteotomy (which in the opinion of the Chief Investigator, Principal Investigator and/or the clinical members of the TMG deems the patient unsuitable for the trial)**
3. Patients who have had a prior adverse reaction to carbamazepine or similar drugs such as oxcarbazepine, or to any related tricyclic antidepressants.
4. Patients known to have atrioventricular block
5. Patients who have a history of bone marrow suppression/depression
6. Patients who have evidence of chronic hepatic or renal impairment
7. Patients who have acute intermittent porphyria
8. Patients who have received a monoamine oxidase inhibitor within 14 days of commencing therapy
9. Patients who have abnormal blood screening results at the time of treatment initiation will be excluded unless the Investigator believes the abnormality to be non-significant clinically
10. Patients of Han Chinese, Thai and other Asian origins who carry the HLA-B*1502 allele
*Skeletal maturity will be assessed as part of the eligibility criteria. Individuals who may reach skeletal maturity before the end of the study should not be included. Patients will be assessed clinically on a case-by-case basis through discussion of the site PI with the CI and/or the clinical members of the TMG during the screening process.
If a participant reaches skeletal maturity during the treatment phase of the trial, they will be asked to continue on the trial for an additional 6 months from the point of skeletal maturity. Patients will stay on their medication and attend study visits, to evaluate if CBZ may have any effect on MCDS patients after they reach skeletal maturity.
**Patients who have planned surgery or planned osteotomy will not automatically be ineligible for the trial. Every potential participant with planned surgery or osteotomy will be assessed clinically on a case-by-case basis through discussion of the site PI, with the CI and/or the clinical members of the TMG during the screening process.
Previous exclusion criteria:
1. Reached skeletal maturity
2. Prior adverse reaction to carbamazepine or similar drugs such as oxcarbazepine, or to any related tricyclic antidepressants.
3. Have atrioventricular block
4. History of bone marrow suppression/depression
5. Evidence of chronic hepatic or renal impairment
6. Acute intermittent porphyria
7. Received a monoamine oxidase inhibitor within 14 days of commencing therapy
8. Abnormal blood screening results at the time of treatment initiation will be excluded unless the Investigator believes the abnormality to be non-significant clinically
9. Patients of Han Chinese, Thai and other Asian origins who carry the HLA-B*1502 allele
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Current primary outcome measures as of 16/05/2024:<br>1. Laboratory safety assessments, adverse events and physical examinations collected post IMP administration<br>2. Outcome of dose-titration safety review at 6 months post IMP treatment initiation<br><br>Stage 2:<br>1. Alteration from baseline in growth velocity over 12 months<br>2. Growth velocity follow-up data at 12 months post treatment initiation<br><br>Previous primary outcome measures:<br>Stage 1:<br>1. Laboratory safety assessments at screening, month 0, month 6 and month 12<br>2. Adverse events and physical examinations collected over a 12-month period post IMP administration<br>3. Outcome of dose-titration safety review at 3 and 12 months post IMP treatment initiation<br><br>Stage 2:<br>1. Growth velocity at baseline and over 24 months<br>2. Growth velocity follow-up data at 24 months post treatment initiation
- Secondary Outcome Measures
Name Time Method