Safety and Efficacy of Asfotase Alfa in Juvenile Patients With Hypophosphatasia (HPP)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00952484
• Date of registration: 03/08/2009
• Prospective Registration: Yes
• Primary sponsor: Alexion Pharmaceuticals
• Public title: Safety and Efficacy of Asfotase Alfa in Juvenile Patients With Hypophosphatasia (HPP)
• Scientific title: A Randomized, Open-Label, Multicenter, Multinational, Dose-Ranging, Historical Control Study of the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of ENB-0040 (Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein) in Children With Hypophosphatasia (HPP)
• Date of first enrolment: September 2009
• Target sample size: 13
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00952484
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Canada, United States

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Written informed consent from parent or legal guardian prior to participation

2. Patients > 5 and < 12 years of age with open growth plates at time of enrollment

3. Tanner stage of 2 or less indicating pre-pubescence

4. Documented history of HPP, as evidenced by:

- Presence of HPP-related rickets on skeletal radiographs of the wrist and knee

- Serum alkaline phosphatase (ALP) below age-adjusted normal range

- Plasma PLP at least twice the upper limit of normal

5. 25(OH) vitamin D level > 20 ng/mL

6. Ability of patient and parent/guardian to comply with study requirements

Exclusion Criteria:

1. Serum calcium or phosphorus below age-adjusted normal range

2. History of sensitivity to any study drug constituent

3. Medical condition, serious intercurrent illness, or other extenuating circumstance
that, in the opinion of the Investigator, may significantly interfere with study
compliance, including all prescribed evaluations and follow-up activities

4. Treatment with an investigational drug within 1 month before start of study drug

5. Current enrollment in any other study involving an investigational new drug, device,
or treatment for HPP (e.g., bone marrow transplantation)

6. Current evidence of a treatable form of rickets

7. Prior treatment with bisphosphonates

8. Bone fracture or orthopedic surgery within the past 12 months that, in the opinion of
the Investigator would interfere with the ability of study patient to comply with
study protocol

9. Major congenital abnormality other than those associated with HPP



Age minimum: 5 Years
Age maximum: 12 Years
Gender: All

Health Condition(s) or Problem(s) studied

Hypophosphatasia (HPP)

Intervention(s)

Biological: asfotase alfa

Primary Outcome(s)

Change in Rickets Severity on Skeletal Radiographs From Baseline to Week 24 as Measured by the Radiographic Global Impression of Change (RGI-C) Scale [Time Frame: Baseline and Week 24]

Secondary Outcome(s)

Change in Biomarkers of Asfotase Alfa Activity as Measured by Plasma Inorganic Pyrophosphate (PPi) [Time Frame: Baseline and Week 24]

Maximum Serum Concentration of Asfotase Alfa (Cmax). [Time Frame: Study Week 1 (0 to 48 hours post-dose)]

Area Under Serum Concentration-time Curve to Last Measurable Concentration of Asfotase Alfa (AUCt) [Time Frame: Study Week 6 (0 to 48 hours post-dose).]

Change in Biomarkers of Asfotase Alfa Activity as Measured by Pyridoxal-5'-Phosphate (PLP) [Time Frame: Baseline and Week 24]

Time at Maximum Serum Concentration of Asfotase Alfa (Tmax) [Time Frame: Study Week 1 (0 to 48 hours post-dose)]

Change in Height (Z-scores) [Time Frame: Baseline and Week 24]

Change in Osteomalacia - Mineralization Lag Time (as Measured by Trans-iliac Crest Bone Biopsy) [Time Frame: Baseline and Week 24]

Maximum Serum Concentration of Asfotase Alfa (Cmax). [Time Frame: Study Week 6 (0 to 48 hours post-dose)]

Time at Maximum Serum Concentration of Asfotase Alfa (Tmax). [Time Frame: Study Week 6 (0 to 48 hours post-dose)]

Area Under Serum Concentration-time Curve to Last Measurable Concentration of Asfotase Alfa (AUCt) [Time Frame: Study Week 1 (0 to 48 hours post-dose)]

Change in Osteomalacia - Osteoid Thickness (as Measured by Trans-iliac Crest Bone Biopsy) [Time Frame: Baseline and Week 24]

Change in Osteomalacia - Osteoid Volume/Bone Volume (as Measured by Trans-iliac Crest Bone Biopsy) [Time Frame: Baseline and Week 24]

Secondary ID(s)

ENB-006-09

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 26/07/2011
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00952484