Safety and Efficacy of Multiple Dosing Regimens of BPS804 in Post Menopausal Women With Low Bone Mineral Density

Study Overview
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Brief Summary
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This study is designed to provide information on the safety, tolerability, pharmacokinetics (PK) and bone biomarker response following multiple BPS804 administration in multiple dosing regimens. This information will permit a comparison of the possible risks and benefits of different dosing regimens of the study drug to enable optimal doses and dose intervals to be tested in subsequent studies.

Detailed Description
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This study was conducted and previously posted by Novartis. The record was transferred to Ultragenyx in February 2021.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multiple Dose Study to Assess the Safety and Efficacy of Multiple Dosing Regimens of BPS804 in Post Menopausal Women With Low Bone Mineral Density

Conditions
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Osteopenia, Osteoporosis

Intervention / Treatment
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* Drug: BPS804 20mg/Kg
* Drug: Placebo to 20mg/Kg BPS804


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women (natural or surgically induced menopause) Low bone mineral density (BMD), as defined by a T score or equivalent BMD absolute value (g/cm2) for lumbar spine of between -2.0 and -3.5, inclusive Body mass index (BMI) must be within the range of 18 to 35kg/m2. Subjects must weigh between 45 and 120kg inclusive to participate. 25-(OH) vitamin D serum level of ≥ 15ng/ml Serum calcium within normal limits Exclusion Criteria: Subjects with suspected neural foraminal stenosis (e.g., cervical, spinal, lumbar), or history of Bell's palsy, cranial nerve disorders, temporomandibular joint and muscle disorders. Subjects who have an increased baseline risk of osteosarcoma: Paget's disease of the bone or unexplained and clinically significant elevations of alkaline phosphatase and/or subjects who have received radiation therapy involving the skeleton. Subjects with any known bone diseases other than postmenopausal osteoporosis. Subjects with a history of an osteoporotic fracture (e.g., vertebral fracture, fragility fracture of the wrist, radius, humerus, hip, or pelvis). Subjects who are regularly using or have regularly used agents affecting bone metabolism: Calcitonin, estrogen, SERMs (raloxifene, Tamoxifen, etc.), Tibolone progestin, or androgens within the last three (3) months prior to screening. Any oral bisphosphonate, lithium chloride, fluoride or systemic glucocorticosteroids (p.o. or i.v.) where the total dose exceeds 750 mg of prednisone or equivalent within the last year prior to screening. Any previous use of denusomab (ProliaTM), parathyroid hormone (ForteoTM), and/or PTH analogs, strontium ranelate, or parenteral formulations of bisphosphonates. Current disease(s) known to influence calcium metabolism including hyperparathyroidism, hypoparathyroidism, hypocalcemia or hypercalcemia. Any disease, abnormality or deformation of the spine (e.g., scoliosis, ankylosing spondylitis, osteophytes) or hip (e.g., joint prosthesis) which would preclude the proper acquisition of a lumbar spine DXA (L1-L4) or femur DXA, respectively. Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BPS804 dosing frequency 1<br>Subjects dosed 20mg/Kg BPS804 monthly | Drug: BPS804 20mg/Kg<br> <br> |
| Placebo Comparator: placebo dosing frequency 1<br>Subjects dosed with matching placebo to 20mg/Kg BPS804 monthly | Drug: Placebo to 20mg/Kg BPS804<br> <br> |
| Experimental: BPS804 dosing frequency 2<br>Subjects dosed with 20mg/Kg BPS804 quarterly | Drug: BPS804 20mg/Kg<br> <br> |
| Placebo Comparator: placebo dosing frequency 2<br>Subjects dosed with matching placebo to 20mg/Kg BPS804 every 3 months | Drug: Placebo to 20mg/Kg BPS804<br> <br> |
| Experimental: BPS804 dosing frequency 3<br>Subjects dosed with 20mg/Kg BPS804 weekly | Drug: BPS804 20mg/Kg<br> <br> |
| Placebo Comparator: Placebo dosing frequency 3<br>Subjects dosed with matching placebo to 20mg/Kg BPS804 weekly | Drug: Placebo to 20mg/Kg BPS804<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to month 9 in bone mineral density at the lumbar spine for the individual BPS804 groups and pooled placebo arms. |  | 9 months | 
| The number (percent) of subjects experiencing adverse events or serious adverse events |  | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline during 9 months of serological bone biomarkers for the individual BPS804 groups and pooled placebo arms. |  | 9 months | 
| Characterization of the PK profile of BPS804: area under the plasma concentration-time curve (AUC) |  | 260 days | 
| Characterization of the PK profile of BPS804: time to reach the maximum Characterization of the PK profile of BPS804: maximum plasma concentration (Cmax) |  | 260 days | 
| Characterization of the PK profile: time to reach the maximum concentration (Tmax) |  | 260 days | 
| Characterization of the PK profile of BPS804: half-life (T1/2) |  | 260 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteopenia, osteoporosis, low bone mineral density