A clinical study to evaluate the safety and preliminary efficacy of BPS804 in adults with hypophosphatasia

• Register: EUCTR
• Last refreshed on: 7 January 2013
• Main ID: EUCTR2010-024013-31-DE
• Date of registration: 07/02/2011
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A clinical study to evaluate the safety and preliminary efficacy of BPS804 in adults with hypophosphatasia
• 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
• Date of first enrolment: 30/06/2011
• Target sample size: 9
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-024013-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Germany

Contacts

• Name: Novartis Pharma GmbH
• Affiliation: Medizinischer Infoservice

• Name: Novartis Pharma GmbH
• Affiliation: Medizinischer Infoservice

Key inclusion & exclusion criteria

Inclusion criteria:
•Male and female patients 18 to 75 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 decidious 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 =10 ng/mL.
•Normocalcemia with serum calcium =8.5 mg/dL and =10.2 mg/dL (or
according to local laboratory ranges).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

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 one of either the lumbar spine or the hip BMD by DXA.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Hypophosphatasia (HPP) is a rare genetic metabolic disorder which results in impaired skeletal mineralization, and which is caused by the absence of or by deficient enzymatic activity of the tissue-nonspecific alkaline phosphatase (TNSALP)
MedDRA version: 14.1 Level: PT Classification code 10049933 Term: Hypophosphatasia System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: BPS804
Product Code: BPS804
Pharmaceutical Form: Powder and solvent for solution for infusion
Current Sponsor code: BPS804
Other descriptive name: fully human IgG2 lambda monoclonal antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Primary end point(s): Primary Objectives

•To evaluate safety and tolerability of BPS804 when administered as multiple, dose escalating i.v. infusions in adults with hypophosphatasia (HPP)

•To determine the pharmacodynamic (PD) effect and preliminary efficacy of BPS804 when administered as multiple, dose escalating i.v. infusions on the serum bone formation marker bone-specific alkaline phosphatase (BSAP) and serum tissue non-specific alkaline phosphatase (TNSALP)

Timepoint(s) of evaluation of this end point: Over 21 weeks

Main Objective: Primary Objectives

•To evaluate safety and tolerability of BPS804 when administered as multiple, dose escalating i.v. infusions in adults with hypophosphatasia (HPP)

•To determine the pharmacodynamic (PD) effect and preliminary efficacy of BPS804 when administered as multiple, dose escalating i.v. infusions on the serum bone formation marker bone-specific alkaline phosphatase (BSAP) and serum tissue non-specific alkaline phosphatase (TNSALP)

Secondary Objective: Secondary Objectives

•To determine the pharmacokinetic (PK) profile of BPS804 when administered as multiple, dose escalating i.v. infusions

•To determine the PD effect of BPS804 on biomarkers as measured by plasma inorganic pyrophosphate (PPi), plasma pyridoxal-5'-phosphate (PLP), plasma phosphoethanolamine (PEA), serum parathyroid hormone (PTH)

•To describe the total/free sclerostin in serum following multiple, dose escalating i.v. infusions of BPS804

•To assess the potential immunogenicity of BPS804 when administered as multiple, dose escalating i.v. infusions

Secondary Outcome(s)

Secondary end point(s): Multiple endpoints will be assessed in this trial, related to efficacy, pharmacodynamics, safety, pharmacokinetics.

Timepoint(s) of evaluation of this end point: Over 21 weeks

Secondary ID(s)

CBPS804A2202

Source(s) of Monetary Support

Novartis Pharma Services AG