Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of Burosumab in Patients Less Than 1 Year of Age
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|ClinicalTrials.gov Identifier: NCT04188964|
Recruitment Status : Recruiting
First Posted : December 6, 2019
Last Update Posted : July 13, 2020
A Phase 1/2, Open-label, Multicenter, Non-randomized Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of Burosumab in Pediatric Patients from Birth to Less than
1 Year of Age with X-linked Hypophosphatemia (XLH)
|Condition or disease||Intervention/treatment||Phase|
|X-linked Hypophosphatemia (XLH)||Drug: Burosumab||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1/2, Open-label, Multicenter, Non-randomized Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of Burosumab in Pediatric Patients From Birth to Less Than 1 Year of Age With X-linked Hypophosphatemia (XLH)|
|Actual Study Start Date :||February 26, 2020|
|Estimated Primary Completion Date :||February 2023|
|Estimated Study Completion Date :||April 2024|
Pediatric subjects > = 6 months to < 12 months will receive a starting dose of 0.4mg/kg administered subcutaneously (SC) every 2 weeks (Q2W) for 64 weeks with the option of the dose to be increased to 0.8mg/kg upon recommendation of the Data Safety Management Board (DSMB). The dose can be either increased up to a maximum of 2 mg/kg or decreased to 0.2 mg/kg depending on serum phosphate response. Upon recommendation of the DSMB subjects < 6 months can then start at 0.4mg/kg starting dose administered subcutaneously (SC) every 2 weeks (Q2W) for 64 weeks with the option to be increased to 0.8mg/kg upon recommendation of the DSMB and can be either increased up to a maximum of 2 mg/kg or decreased to 0.2 mg/kg depending on serum phosphate response.
Burosumab is a sterile clear colourless and preservative free solution supplied in single use 5ml vials containing 1 mL of Burosumab at a concentration of 10mg/mL,20 mg/mL or 30mg/mL
- Safety and tolerability of burosumab will be measured in subjects with XLH starting treatment below 12 months of age by studying the number, severity and relatedness of Adverse Events (including laboratory and imaging assessments). [ Time Frame: From baseline, measured throughout the study up to Week 64. ]Incidence, frequency, and severity of AEs and SAEs, including clinically significant changes in laboratory assessments as well as ECHO, ECG, ultrasound and X-Ray images.
- The number of participants showing an effect of burosumab on pharmacodynamic (PD) markers of phosphate homeostasis. [ Time Frame: Baseline, (Week 20, 32, 40, 48, 56 and 64). ]Number of participants with changes in serum phosphate and 1,25(OH)2D.
- To characterize the pharmacokinetics (PK) of burosumab following subcutaneous (SC) injection. [ Time Frame: Baseline, (Day 3, 7, 11, and 14, Week 4, 6, 8, 12, 16, 40, 64) ]Burosumab serum concentrations and PK parameters.
- The number of participants with change in serum ALP showing clinical effects of burosumab on growth and prevention and/or healing of rickets and skeletal deformities. [ Time Frame: Baseline, Week 40 and 64. ]Change in serum ALP.
- Growth and prevention and/or healing of rickets and skeletal deformities will be measured by comparing radiographs taken at baseline to x rays at the following timepoints: [ Time Frame: Baseline, Week 40 and 64. ]Change in time of appearance in radiographic appearance of rickets severity as assessed by the RGI-C scoring system a seven-point scale (-3=severe worsening, 0=no change; +3=near/complete healing),
- Appearance in rickets severity assessed by total rickets severity score (RSS) [ Time Frame: Baseline, Week 40 and 64. ]Change in appearance in rickets severity assessed by total rickets severity score (RSS) a 10-point radiographic scoring method where 10 represents the most extreme degree of rickets severity and 0 represents the absence of radiographic changes of rickets.
- Lower extremity skeletal abnormalities, determined by the radiographic global impression of change (RGI-C) long leg score including genu varum and genu valgus, as determined by the RGI-C long leg score at Week 40 and 64. [ Time Frame: Baseline, Week 40 and 64. ]Change in lower extremity skeletal abnormalities, including genu varum and genu valgus, as determined by the RGI-C long leg scale score ranging from -3 (very much worse, or severe worsening of rickets) to +3 (very much better, or complete or near complete healing of rickets)
- The number of participants with change in recumbent length. [ Time Frame: Baseline, at Week 40 and Week 64 ]Change in recumbent length measured in centimetres to calculate height-for age z scores, and percentiles
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04188964
|Contact: Development Division Project Management Departmentfirstname.lastname@example.org|
|Centre de reference des maladies renales rares-Hospices Civils de Lyon-Hopital Femme Mere Enfant||Recruiting|
|Contact: Justine Bacchetta, Prof|
|Hopital Kremlin APHP||Recruiting|
|Contact: Agnes Linglart, Prof|