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NCT Number: NCT00744042

Safety and Efficacy Study of Asfotase Alfa in Severely Affected Infants With Hypophosphatasia (HPP)

This clinical trial studies the safety and efficacy of asfotase alfa in infants and young children with infantile onset HPP.

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Key information

Conditions

Hypophosphatasia (HPP) Avitaminosis Bone Diseases Bone Diseases, Metabolic Calcium Metabolism Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Deficiency Diseases Genetic Diseases, Inborn Hypophosphatasia Malnutrition Metabolic Diseases Metabolism, Inborn Errors Metal Metabolism, Inborn Errors Musculoskeletal Diseases Nutrition Disorders Nutritional and Metabolic Diseases Osteomalacia Rickets Vitamin D Deficiency

Age range

Up to 36 month

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

The University of Manitoba Health Sciences Centre, Winnipeg, Manitoba, Canada

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About this study

Hypophosphatasia (HPP) is a life-threatening, genetic, and ultra-rare metabolic disease characterized by defective bone mineralization and impaired phosphate and calcium regulation that can lead to progressive damage to multiple vital organs, including destruction and deformity of bones, profound muscle weakness, seizures, impaired renal function, and respiratory failure. There are no approved disease-modifying treatments for patients with this disease. There is also limited data available on the natural course of this disease over time, particularly in patients with the juvenile-onset form.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Legal guardian(s) must provide informed consent prior to any study procedures
  • Documented diagnosis of severe HPP as indicated by:
  • Total serum alkaline phosphatase at least 3 standard deviations (SD) below the mean for age
  • Plasma pyridoxal 5'-phosphate (PLP) at least 4 times the upper limit of normal
  • Radiographic evidence of HPP (hypophosphatasia), characterized by:
  • Flared and frayed metaphyses
  • Severe, generalized osteopenia
  • Widened growth plates
  • One or more HPP-related findings:
  • History or presence of:
  • Non-traumatic post-natal fracture
  • Delayed fracture healing
  • History of elevated serum calcium
  • Functional craniosynostosis with decreased head circumference growth
  • Nephrocalcinosis
  • Respiratory compromise
  • Rachitic chest deformity and/or vitamin B6 dependent seizures
  • Failure to thrive
  • Onset of symptoms prior to 6 months of age
  • Age ≤ 36 months
  • Otherwise medically stable (patient may be on ventilatory support)
  • Legal guardian(s) must be willing to comply with the study

Exclusion criteria

  • History of sensitivity to any of the constituents of the study drug
  • 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
  • Treatment with an investigational drug within 1 month prior to the start of study drug administration
  • Current enrollment in any other study involving an investigational new drug, device or treatment for HPP (e.g., bone marrow transplantation)
  • Low serum calcium, phosphate or 25(OH) vitamin D
  • Current evidence of a treatable form of rickets
  • Prior treatment with bisphosphonate

Treatment and study plan

Asfotase Alfa

Biological

Other names: Asfotase Alfa was formerly referred to as ENB-0040, Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein

Primary outcomes

  1. Change in Rickets Severity From Baseline to Week 24, Based on Assessment of Skeletal Radiographs Using Radiologic Global Impression of Change (RGI-C)

    Time frame: 24 weeks

    A 7-point RGI-C (Radiographic Global Impression of Change) score was used to rate change in rickets severity. Scores ranged from -3 (severe worsening of rickets) to +3 (complete healing of rickets). Only those patients with a minimum score of +2 indicating substantial healing of rickets) were considered "responders". Three pediatric radiologists not affiliated with the conduct of the study performed the ratings. Average scores were derived for each patient at each assessment.

Secondary outcomes

  1. Maximum Serum Concentration of Asfotase Alfa (Cmax)

    Time frame: Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose)

    Maximum serum concentration observed during intensive PK sampling interval.

  2. Time at Maximum Serum Concentration of Asfotase Alfa (Tmax)

    Time frame: Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose).

    Time at maximum serum concentration observed during intensive PK sampling interval.

  3. Area Under Serum Concentration-time Curve to Last Measurable Concentration of Asfotase Alfa (AUCt)

    Time frame: Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose).

    Area under serum concentration-time curve to last measurable concentration during intensive PK sampling interval.

Sponsors and collaborators

Lead sponsor

Alexion Pharmaceuticals, Inc.

Industry

Registry information

Official study title

A Multicenter, Open-Label Study of the Safety, Tolerability and Pharmacology of Asfotase Alfa in up to 10 Severely Affected Patients With for the Treatment of Severely Affected Patients With Infantile Hypophosphatasia (HPP)

Important dates

Study start
2008
Primary completion
2010
Study completion
2010
First posted
Aug 29, 2008
Registry last updated
Apr 1, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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