E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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) |
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E.1.1.1 | Medical condition in easily understood language |
Hypophosphatasia is characterized by defective mineralization of bone and/or teeth in the presence of low activity of a serum and bone enzyme, alkaline phosphatase. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10049933 |
E.1.2 | Term | Hypophosphatasia |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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)
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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). |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | 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)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Multiple endpoints will be assessed in this trial, related to efficacy, pharmacodynamics, safety, pharmacokinetics. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Please refer to Section 5.5.10 of the CBPS804A2202 Protocol.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |