Setrusumab vs bisphosphonates in children from 2 to < 7 years old with osteogenesis imperfecta (OI)

• The study is sponsored by Ultragenyx.
• The purpose of the study is to evaluate the new medication, setrusumab, an anti-sclerostin monoclonal antibody, by comparing its effects to IV-Bisphosphonate (BP) therapy in children with OI Types I, III, or IV who have a recent history of fractures.
• After a screening visit to determine eligibility, subjects are randomized to either receive setrusumab at their Baseline Visit or to resume their IV BP therapy, for up to 24 months. At the end of this controlled comparison period, subjects assigned to the IV-BP arm will be allowed to transition to setrusumab. During this Extension Period, all subjects will be offered setrusumab for a minimum of 12 months.

• The following procedures are scheduled to occur at various visits during the course of the study – physical examination, skeletal assessments including X-rays and bone density, questionnaires, audiometry and assessment of blood and urinary tests. Setrusumab will be administered monthly to those children randomized to that treatment.

Key Inclusion Criteria:

• Male or female 2 to < 7 years of age

• Clinical diagnosis of OI Types I, III, or IV confirmed by identification of genetic mutation in COL1A1 or COL1A2

• History of ≥ 1 fracture in the past 12 months, ≥ 2 fractures in the past 24 months, or
• ≥ 1 femur, tibia, or humerus fracture in the past 24 months

• Any prior exposure to, or currently receiving, IV-bisphosphonate therapy for treatment of OI

Key Exclusion Criteria:

• Contraindication for IV BP treatment

• History of skeletal malignancies or bone metastases, neural foraminal stenosis (except if due by scoliosis), or Chiari malformation

• History of or current uncontrolled concomitant diseases that may impact bone metabolism, such as hypo/hyperparathyroidism, abnormal thyroid function, nephrotic syndrome, or Stage IV/V renal disease

• Any skeletal condition (other than OI) leading to bone deformity and/or increased risk of fractures, such as rickets, osteopetrosis, idiopathic juvenile osteoporosis, or skeletal dysplasia