Safety and Efficacy Study of Asfotase Alfa in Severely Affected Infants With Hypophosphatasia (HPP)
This study has been completed.
Sponsor:
Alexion International Sàrl
Information provided by (Responsible Party):
Alexion International Sàrl
ClinicalTrials.gov Identifier:
NCT00744042
First received: August 27, 2008
Last updated: January 24, 2013
Last verified: December 2011
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Purpose
This Clinical Trial is being conducted to study the safety and efficacy of an investigational drug Asfotase Alfa for the treatment of infants with hypophosphatasia (HPP).
| Condition | Intervention | Phase |
|---|---|---|
|
Hypophosphatasia |
Biological: Asfotase Alfa |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Study of Asfotase Alfa (Human Recombinant Tissue Non-specific Alkaline Phosphatase Fusion Protein) for the Treatment of Severely Affected Patients With Infantile Hypophosphatasia (HPP) |
Resource links provided by NLM:
Further study details as provided by Alexion International Sàrl:
Primary Outcome Measures:
- Number of Patients Showing Radiographic Response After 24 Weeks of Treatment [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]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.
- Number of SAEs (Serious Adverse Events) for All Treated Patients [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]The number and description of all SAEs experienced by treated pateints were reported and classified according to the relationship to treatment
| Enrollment: | 11 |
| Study Start Date: | September 2008 |
| Study Completion Date: | May 2010 |
| Primary Completion Date: | May 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Asfotase Alfa |
Biological: Asfotase Alfa
All patients receive a single IV (intravenous) dose of 2 mg/kg followed by 7 days of observation. Patients then begin thrice weekly SC (subcutaneous) injections of Asfotase Alfa at a dose of 1 mg/kg for 23 weeks. The total duration of the study is 24 weeks.
Other Names:
|
Detailed Description:
Hypophosphatasia (HPP) is a rare inherited form of rickets and osteomalacia caused by inactivating mutations in the gene encoding the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Low circulating levels of alkaline phosphatase with elevated serum or urine levels of the TNSALP substrates inorganic pyrophosphate (PPi), pyridoxal 5'-phosphate (PLP) and phosphoethanolamine (PEA) are the biochemical hallmarks of the disease. Disease severity in HPP is inversely related to the age at symptom presentation. The most severe cases occur in utero and almost invariably result in death, generally due to pulmonary compromise. Infants who present in the first six months of life have about 50% mortality.
Eligibility| Ages Eligible for Study: | up to 36 Months |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00744042
Locations
| United States, Arkansas | |
| Arkansas Children's Hospital | |
| Little Rock, Arkansas, United States, 72202 | |
| United States, Delaware | |
| Nemours/Alfred I. duPont Hospital for Children | |
| Wilmington, Delaware, United States, 19803 | |
| United States, Missouri | |
| St. John's Children's Hospital | |
| Springfield, Missouri, United States, 65804 | |
| United States, Nebraska | |
| University of Nebraska Children's Hospital & Medical Center | |
| Omaha, Nebraska, United States, 68114 | |
| United States, Tennessee | |
| Children's Hospital at Vanderbilt | |
| Nashville, Tennessee, United States, 37232 | |
| United States, Wisconsin | |
| St. Vincent Hospital | |
| Green Bay, Wisconsin, United States, 54301 | |
| Canada, Manitoba | |
| Department of Pediatrics & Child Health, Health Sciences Centre Winnipeg, University of Manitoba | |
| Winnipeg, Manitoba, Canada, R3A 1S1 | |
| United Arab Emirates | |
| Tawam Hospital | |
| Al Ain, Abu-Dhabi, United Arab Emirates | |
| United Kingdom | |
| Sheffield Children's Hospital | |
| Sheffield, England, United Kingdom, S10 2TH | |
Sponsors and Collaborators
Alexion International Sàrl
Investigators
| Principal Investigator: | Cheryl Rockman-Greenberg, MD | The University of Manitoba Health Sciences Centre, Winnipeg MB Canada |
| Principal Investigator: | Jill H Simmons, MD | Vanderbilt Children's Hospital, Nashville TN USA |
| Principal Investigator: | Martin L Bauer, MD | Arkansas Children's Hospital, Little Rock AR USA |
| Principal Investigator: | Nick Bishop, MD | Sheffield Children's Hospital, Sheffield Great Britain UK |
| Principal Investigator: | Terrance S Edgar, MD | St. VIncent's Hospital, Green Bay WI USA |
| Principal Investigator: | Nada J Salman, MD | Tawam-Johns Hopkins Hospital, Al Ain Abu-Dhabi UAE |
| Principal Investigator: | Stanley Craig, MD | Royal Belfast Hospital for Sick Children, Belfast Northern Ireland UK |
| Principal Investigator: | Michael B Bober, MD | Alfred I. duPont Hospital for Children, Wilmington DE USA |
| Principal Investigator: | Jean N Moore, MD | St. John's Hospital, Springfield MO USA |
| Principal Investigator: | Richard E Lutz, MD | University of Nebraska Medical Center, Omaha NE USA |
More Information
Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Alexion International Sàrl |
| ClinicalTrials.gov Identifier: | NCT00744042 History of Changes |
| Other Study ID Numbers: | ENB-002-08 |
| Study First Received: | August 27, 2008 |
| Results First Received: | May 15, 2011 |
| Last Updated: | January 24, 2013 |
| Health Authority: | United States: Food and Drug Administration Canada: Health Canada |
Keywords provided by Alexion International Sàrl:
|
genetic metabolic disorder alkaline phosphatase tissue non-specific alkaline phosphatase rickets osteomalacia |
Additional relevant MeSH terms:
|
Hypophosphatasia Metal Metabolism, Inborn Errors Metabolism, Inborn Errors Genetic Diseases, Inborn Metabolic Diseases |
ClinicalTrials.gov processed this record on May 19, 2013