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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 September 2022
• Main ID: NCT01406977
• Date of registration: 29/07/2011
• Prospective Registration: No
• Primary sponsor: Ultragenyx Pharmaceutical Inc
• Public title: Dose Escalation Study to Evaluate the Safety and Tolerability of Multiple Infusions of BPS804 in Adults With Hypophosphatasia (HPP)
• Scientific title: An Open-label, Intra-patient Dose-escalation Study to Evaluate the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Multiple Infusions of BPS804 in Adults With Hypophosphatasia (HPP).
• Date of first enrolment: July 2011
• Target sample size: 8
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01406977
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Germany

Contacts

• Name: Medical Director
• Affiliation: Ultragenyx Pharmaceutical Inc

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Hypophosphatasia

Intervention(s)

Drug: BPS804

Primary Outcome(s)

The number (percent) of patients experiencing adverse events or serious adverse events [Time Frame: 141 days following initial investigational product administration]

Change from baseline in primary serological bone biomarkers [Time Frame: 141 days following initial investigational product administration]

Secondary Outcome(s)

Characterization of the pharmacokinetic profile of BPS804: area under the plasma concentration-time curve (AUC) [Time Frame: 1, 29 and 141 days following initial investigational product administration]

Characterization of the pharmacokinetic profile of BPS804: time to reach the maximum concentration (Tmax) [Time Frame: 1, 15 and 29 days following initial investigational product administration]

The number (percent) of patients developing anti-BPS804 antibodies [Time Frame: 141 days following initial investigational product administration]

Characterization of the pharmacokinetic profile of BPS804: observed maximum plasma concentration following drug administration (Cmax) [Time Frame: 1, 15 and 29 days following initial investigational product administration]

Change from baseline in secondary biomarkers [Time Frame: 141 days following initial investigational product administration]

Secondary ID(s)

2010-024013-31

CBPS804A2202

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Novartis

Mereo BioPharma