Dose Escalation Study to Evaluate the Safety and Tolerability of Multiple Infusions of BPS804 in Adults With Hypophosphatasia (HPP)

The purpose of the study is to determine tolerability, PK/PD and preliminary efficacy of BPS804 in adult patients with HPP treated with multiple escalating doses of BPS804.

This study will allow a comparison of several doses of the study drug within the first two weeks after administration and after a longer assessment period for the highest dose level to enable selection of dose ranges to be tested in subsequent studies in the HPP indication.

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

Eligibility Criteria:
Inclusion Criteria:

* Male and female patients 18 to 60 years of age in good health (other than pre-established clinical diagnosis of HPP) as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
* Previously established clinical diagnosis of HPP with confirmed ALPL mutation by genetic test and as manifested by:
* Serum alkaline phosphatase levels below the age-adjusted normal range and
* Radiologic evidence of osteopenia or osteomalacia or
* History of plasma PLP at least twice the upper limit of normal range or
* History of rickets, or history of premature loss of deciduous teeth, or bone deformity consistent with osteomalacia or past rickets, or past non-traumatic fracture, pseudofracture, or non-healing fracture.
* 25-(OH) vitamin D3 serum level of ≥20 ng/mL.
* Normocalcemia with serum calcium ≥8.5 mg/dL and ≤10.2 mg/dL and normal phosphate levels (2.4 - 4.1 mg/dL) (or according to local laboratory ranges).

Exclusion Criteria:

* A history of clinically significant ECG abnormalities.
* History of malignancy of any organ system (other than localized basal cell carcinoma of the skin and for skeletal malignancies see below), within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
* History of skeletal malignancies or bone metastases at any time.
* History of external beam radiation to the skeleton.
* Open epiphyses as judged by the Investigator based on previous clinical assessments.
* Patients with suspected neural foraminal stenosis (e.g., at cervical, spinal, or lumbar site) as judged by the Investigator which could be caused by disc herniation and are described as sciatic pain, tingling, burning sensation with numbness and/or weakness.
* History of or concomitant diseases such as hypo-/hyperparathyroidism, hypo-/hyperthyroidism, Pagets disease, previous neck surgery involving partial or complete thyroidectomy and abnormal thyroid function or thyroid disease or other endocrine disorders or conditions.
* Treatment with any anti-resorptive medication (e.g., oral and/or injectable), bisphosphonates and/or teriparatide (e.g., ForteoTM) within the last 6 months.
* Exposure to blood products or monoclonal antibodies within previous 12 months.
* Any deformation of the spine (e.g., severe scoliosis, ankylosing spondylitis) or the hip which would preclude proper acquisition of lumbar spine or hip BMD by DXA.

Other protocol-defined inclusion/exclusion criteria may apply.