Children with Osteogenesis Imperfecta (OI) have bone pain, low bone mass and fractures. There are no approved drugs for the treatment of OI in children, even though some intravenous (IV) bisphosphonates are used off-label in some countries. In a single dose, pharmacokinetic study, data showed that risedronate was well tolerated in 28 children with OI. This three year study will test the safety and efficacy of risedronate in the treatment of children with OI. For the first year, patients will be randomized to the risedronate and placebo groups in a 2:1 ratio. For the second and third years of the study, all patients will receive risedronate.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
143
risedronate tablet once a day for one year followed by risedronate once a day for two years
placebo tablet once a day for one year followed by risedronate once a day for two years
Miami Children's Hospital
Miami, Florida, United States
University of Nebraska Medical Center, Children's Hospital
Omaha, Nebraska, United States
Hospital for Special Surgery
New York, New York, United States
Wright State University BioMedical Imaging Laboratory and Miami Valley Hospital
Dayton, Ohio, United States
Oregon Health & Science University
Portland, Oregon, United States
The Children's Hospital at Westmead
Westmead, New South Wales, Australia
Princess Margaret Hospital for Children
Perth, Australia
Cliniques Universitaires Saint Luc
Brussels, Belgium
Pontificia Universidad Catolica de Chile
Santiago, Chile
Osteocentrum, II. Interní klinika, Fakultní nemocnice Plzeň-Bory
Pilsen, Czechia
...and 10 more locations
Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 12, ITT Population
Lumbar Spine Bone Mineral Density (BMD) measured by dual-energy x-ray absorptiometry (DXA)and read by central reader. Duplicate scans obtained at screening and Month 12.
Time frame: Baseline and Month 12
Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 24, ITT Population
Lumbar Spine Bone Mineral Density (BMD) measured by dual-energy x-ray absorptiometry (DXA)and read by central reader.
Time frame: Baseline and Month 24
Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 36, ITT Population
Lumbar Spine Bone Mineral Density (BMD) measured by dual-energy x-ray absorptiometry (DXA)and read by central reader.
Time frame: Baseline and Month 36
Percent Change From Baseline in Total Body BMD at Month 12, ITT Population
Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.
Time frame: Baseline and Month 12
Percent Change From Baseline in Total Body BMD at Month 24, ITT Population
Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.
Time frame: Baseline and Month 24
Percent Change From Baseline in Total Body BMD at Month 36, ITT Population
Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA.
Time frame: Baseline and Month 36
Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 12, ITT Population
Time frame: Baseline and Month 12
Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 24, ITT Population
Time frame: Baseline and Month 24
Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 36, ITT Population
Time frame: Baseline and Month 36
Percent Change From Baseline in Total Body BMC at Month 12, ITT Population
Time frame: Baseline and Month 12
Percent Change From Baseline in Total Body BMC at Month 24, ITT Population
Time frame: Baseline and Month 24
Percent Change From Baseline in Total Body BMC at Month 36, ITT Population
Time frame: Baseline and Month 36
Lumbar Spine Z-score - Percent Change From Baseline to Month 12, ITT Population
Lumbar Spine Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values".
Time frame: Baseline and Month 12
Lumbar Spine Z-score - Percent Change From Baseline to Month 24, ITT Population
Lumbar Spine Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values".
Time frame: Baseline and Month 24
Lumbar Spine Z-score - Percent Change From Baseline to Month 36, ITT Population
Lumbar Spine Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values".
Time frame: Baseline and Month 36
Total Body Z-score- Percent Change From Baseline to Month 12, ITT Population
Total Body Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values".
Time frame: Baseline and Month 12
Total Body Z-score- Percent Change From Baseline to Month 24, ITT Population
Total Body Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values".
Time frame: Baseline and Month 24
Total Body Z-score- Percent Change From Baseline to Month 36, ITT Population
Total Body Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values".
Time frame: Baseline and Month 36
Percent Change From Baseline in Lumbar Spine Bone Area at Month 12, ITT Population
Measured by DXA.
Time frame: Baseline and Month 12
Percent Change From Baseline in Lumbar Spine Bone Area at Month 24, ITT Population
Measured by DXA.
Time frame: Baseline and Month 24
Percent Change From Baseline in Lumbar Spine Bone Area at Month 36, ITT Population
Measured by DXA.
Time frame: Baseline and Month 36
Percent Change From Baseline in Total Body Bone Area Month 12, ITT Population
Time frame: Baseline and Month 12
Percent Change From Baseline in Total Body Bone Area Month 24, ITT Population
Time frame: Baseline and Month 24
Percent Change From Baseline in Total Body Bone Area Month 36, ITT Population
Time frame: Baseline and Month 36
New Morphometric Vertebral Fracture at Month 12, ITT Population
Morphometric Vertebral Fracture measured by semi-quantitative (SQ) analysis of x-rays using the Genant scoring system at endpoint. (Ref: Genant 1993). SQ-Scores range from 0 (no fracture) to 3 (severe fracture). New fracture = SQ score is 0 at baseline and \>0 at the specified end visit.
Time frame: Baseline and Month 12
New Morphometric Vertebral Fracture at Month 36, ITT Population
Morphometric Vertebral Fracture measured by SQ analysis of x-rays using the Genant scoring system. (Ref: Genant 1993). SQ-Scores range from 0 (no fracture) to 3 (severe fracture). New fracture = SQ score is 0 at baseline and \>0 at the specified end visit.
Time frame: Baseline and Month 36
Categorization by Number of New Morphometric Vertebral Fracture at Month 12, ITT
Patients with 1 or more New Morphometric Vertebral Fracture as measured by SQ analysis of x-rays using the Genant scoring system (Ref: Genant 1993). SQ-Scores range from 0 (no fracture) to 3 (severe fracture). Incidence = SQ score is 0 at baseline and \>0 at post-baseline.
Time frame: Baseline and Month 12
Categorization by Number of New Morphometric Vertebral Fracture at Month 36, ITT
Patients with 1 or more New Morphometric Vertebral Fracture as measured by SQ analysis of x-rays using the Genant scoring system (Ref: Genant 1993). SQ-Scores range from 0 (no fracture) to 3 (severe fracture). Incidence = SQ score is 0 at baseline and \>0 at post-baseline.
Time frame: Baseline and Month 36
Incidence New Vertebral Fractures by SQ (Semi-Quantitative) Score, Patients Aged 4-9 Years, Month 12, ITT Population
Patients aged 4-9 years with new morphometric vertebral fractures as measured by SQ analysis of x-rays using the Genant scoring system at Month 12 +/- 14 days. (Ref: Genant 1993). SQ Score mild - 0/no fracture to Grade 1, Moderate to Severe - change from 0/no fracture to Grade 2-3.
Time frame: Month 12
Incidence New Vertebral Fractures by SQ Score, Patients Aged 10-15 Years, Month 12, ITT Population
Patients aged 10-15 years with new morphometric vertebral fractures as measured by SQ analysis of x-rays using the Genant scoring system at Month 12 +/- 14 days. (Ref: Genant 1993). SQ Score mild - 0/no fracture to Grade 1, Moderate to Severe - change from 0/no fracture to Grade 2-3.
Time frame: Month 12
Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population
Long bones include radius, ulna, humerus, tibia, fibula, femur, upper limb and lower limb fracture.
Time frame: Time to First Event (days) up to 12 Months
Number of Clinical Fractures, Month 12, ITT Population
Long bones include radius, ulna, humerus, tibia, fibula, femur, upper limb and lower limb fracture.
Time frame: 12 Months
Serum BAP - Percent Change From Baseline to Month 12, ITT Population
Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.
Time frame: Baseline and 12 Months
Serum BAP - Percent Change From Baseline to Month 24, ITT Population
Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.
Time frame: Baseline and 24 Months
Serum BAP - Percent Change From Baseline to Month 36, ITT Population
Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment.
Time frame: Baseline and 36 Months
Urine NTX/Cr - Percent Change From Baseline at Month 12, ITT Population
Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.
Time frame: Baseline and Endpoint / Month 12
Urine NTX/Cr - Percent Change From Baseline at Month 24, ITT Population
Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.
Time frame: Baseline and Month 24
Urine NTX/Cr - Percent Change From Baseline at Month 36, ITT Population
Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment.
Time frame: Baseline and Month 36
Wong-Baker FACES Pain Rating Scale - Change From Baseline to Month 12, ITT Population
Wong-Baker FACES Pain Rating Scale (pain assessment scale using facial expressions, translated into a range from 0= no pain \[smiling face\] to 10= worst pain possible \[distorted face with tears\]; negative values indicate decrease in pain). Reference: Wong DL et al.
Time frame: Baseline and Month 12
Bone Age (Years), Change From Baseline to Month 12, ITT Population
Bone Age determined by visual assessment of hand / wrist radiographs.
Time frame: Baseline and Month 12
Bone Age (Years), Change From Baseline to Month 24, ITT Population
Bone Age determined by visual assessment of hand / wrist radiographs.
Time frame: Baseline and Month 24
Bone Age (Years), Change From Baseline to Month 36, ITT Population
Bone Age determined by visual assessment of hand / wrist radiographs.
Time frame: Baseline and Month 36
Annualized Growth Velocity - Change From Baseline to Month 12, ITT Population
Annualized Growth Velocity \[= bone age change from baseline x (365.25/time in days between baseline and the bone age measurement)\]
Time frame: Baseline and Month 12
Annualized Growth Velocity - Change From Baseline to Month 36, ITT Population
Annualized Growth Velocity \[= bone age change from baseline x (365.25/time in days between baseline and the bone age measurement)\]
Time frame: Baseline and Month 36
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