A Multicenter, Open-Label Study of the Safety, Tolerability and Pharmacology of ENB-0040 (Enobia’s human recombinant tissue non-specific alkaline phosphatase fusion protein) in up to 6 Severely Affected Patients with Infantile Hypophosphatasia (HPP)

• Register: EUCTR
• Last refreshed on: 20 March 2012
• Main ID: EUCTR2008-007406-11-GB
• Date of registration: 15/01/2009
• Prospective Registration: Yes
• Primary sponsor: Enobia Canada Limited Partnership
• Public title: A Multicenter, Open-Label Study of the Safety, Tolerability and Pharmacology of ENB-0040 (Enobia’s human recombinant tissue non-specific alkaline phosphatase fusion protein) in up to 6 Severely Affected Patients with Infantile Hypophosphatasia (HPP)
• Scientific title: A Multicenter, Open-Label Study of the Safety, Tolerability and Pharmacology of ENB-0040 (Enobia’s human recombinant tissue non-specific alkaline phosphatase fusion protein) in up to 6 Severely Affected Patients with Infantile Hypophosphatasia (HPP)
• Date of first enrolment: 25/02/2009
• Target sample size: 10
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-007406-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Legal guardian(s) must provide informed consent prior to any study procedures
2. Documented diagnosis of severe HPP as indicated by:
a. Total serum alkaline phosphatase at least 3 standard deviations (SD) below the mean for age
b. Plasma pyridoxal 5’-phosphate at least 4 times the upper limit of normal
c. Radiographic evidence of HPP, characterized by:
* Flared and frayed metaphyses
* Severe, generalized osteopenia
* Widened growth plates
d. One or more HPP-related findings:
* History or presence of
o Non-traumatic post-natal fracture
o Delayed fracture healing
* History of elevated serum calcium
* Functional craniosynostosis with decreased head circumference growth
* Nephrocalcinosis
* Respiratory compromise
e. Rachitic chest deformity and/or vitamin B6 dependent seizures
f. Failure to thrive
3. Onset of symptoms prior to 6 months of age
4. Age = 36 months
5. Otherwise medically stable (patient may be on ventilatory support)
6. Legal guardian(s) must be willing to comply with the study
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. History of sensitivity to any of the constituents of the study drug
2. Current or prior clinically significant cardiovascular, endocrinologic, hematologic,
hepatic, immunologic, metabolic, infectious, urologic, pulmonary, neurologic,
dermatologic, renal condition and/or other major disease which, in the opinion of the
investigator, precludes study participation
3. Treatment with an investigational drug within 1 month prior to the start of study drug
administration
4. Current enrollment in any other study involving an investigational new drug, device
or treatment for HPP (e.g., bone marrow transplantation)
5. Low serum calcium, phosphate or 25(OH) vitamin D
6. Current evidence of a treatable form of rickets
7. Prior treatment with bisphosphonate


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

Health Condition(s) or Problem(s) studied

Infantile Hypophosphatasia
MedDRA version: 14.1 Level: PT Classification code 10049933 Term: Hypophosphatasia System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Code: ENB-0040
Pharmaceutical Form: Solution for injection
Current Sponsor code: ENB-0040
Other descriptive name: Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-

Primary Outcome(s)

Main Objective: 1. To assess the efficacy of ENB-0040 in treating the skeletal manifestations of infantile HPP
2. To determine the safety and tolerability of ENB-0040 given intravenously (IV) in a single dose and subcutaneously (SC) in repeat doses

Primary end point(s): The efficacy of ENB-0040 will be determined by assessing the radiographic changes in skeletal disease. Standard images will be obtained at baseline and at 4, 12 and 24 weeks after initiation of ENB-0040 therapy.

Safety parameters, including spontaneously reported adverse events (AEs), infusion or injection associated reactions, vital signs, physical examination findings, laboratory assessments and anti-ENB-0040 antibody testing will be assessed for changes from baseline. In addition, any change in concomitant medications and therapies will be recorded.

Secondary Objective: 1. To assess the pharmacokinetics (PK) of ENB-0040 given IV and SC
2. To assess the bioavailability of SC ENB-0040

Secondary ID(s)

ENB-002-08