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

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

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.

Study Overview

• Status: Completed
• Conditions: Osteoporosis; Osteopenia
• Intervention / Treatment: Drug: BPS804 20mg/Kg; Drug: Placebo to 20mg/Kg BPS804

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801-2811
      • Novartis Investigative Site
  • Florida
    • Miami, Florida, United States, 33126
      • Novartis Investigative Site
    • Miami, Florida, United States, 33175
      • Novartis Investigative Site
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Novartis Investigative Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Ultragenyx Pharmaceutical Inc
• Collaborators: Novartis; Mereo BioPharma

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: July 11, 2011
• First Submitted That Met QC Criteria: July 28, 2011
• First Posted (Estimate): August 1, 2011

Study Record Updates

• Last Update Posted (Actual): September 15, 2022
• Last Update Submitted That Met QC Criteria: September 9, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: osteoporosis; Osteopenia; low bone mineral density
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Osteoporosis; Bone Diseases, Metabolic; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CBPS804A2203