Open-Label Study of Asfotase Alfa in Infants and Children ≤ 5 Years of Age With Hypophosphatasia (HPP)

NCT ID: NCT01176266

Last Updated: 2019-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2016-09-30

Brief Summary

This clinical trial was conducted to study hypophosphatasia (HPP), a bone disorder caused by gene mutations or changes. These gene mutations cause low levels of an enzyme needed to harden bone. The purpose of this study was to test the safety and efficacy of a study drug called asfotase alfa (human recombinant tissue non-specific alkaline phosphate fusion protein) to see what effects it has on patients 5 years of age or less with HPP.

Detailed Description

Asfotase alfa was formerly referred to as ENB-0040

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 limited data available on the natural course of this disease over time, particularly in patients with the juvenile-onset form.

Conditions

Hypophosphatasia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Asfotase alfa

A total of 6 mg/kg/week of asfotase alfa administered by SC injection (either 1 mg/kg asfotase alfa 6 times per week, or 2 mg/kg asfotase alfa 3 times per week)

Group Type: EXPERIMENTAL

asfotase alfa

Intervention Type: DRUG

Interventions

asfotase alfa

Intervention Type: DRUG

Other Intervention Names

ENB-0040

Eligibility Criteria

Inclusion Criteria

Patients must meet all of the following criteria for enrollment in this study:

1. Parent or legal guardian(s) must provide written informed consent prior to any study procedures being performed and must be willing to comply with all study-required procedures. Where appropriate and required by local regulations, patient assent should also be provided prior to any study procedures being performed.

2. Documented diagnosis of HPP as indicated by:

1. Total serum alkaline phosphatase (ALP) below the lower limit of normal for age NOTE: Historical values for ALP may be used to determine patient eligibility.

2. Plasma pyridoxal-5'-phosphate (PLP) above the upper limit of normal (unless patient is receiving pyridoxine for seizures) NOTE: Historical values for PLP may be used to determine patient eligibility.

3. Radiographic evidence of HPP at screening, characterized by:

• Flared and frayed metaphyses, and
• Severe, generalized osteopenia, and
• Widened growth plates, and
• Areas of radiolucency or sclerosis

4. Two or more of the following HPP-related findings:

• History or presence of: i) Nontraumatic post-natal fracture or ii) Delayed fracture healing
• Nephrocalcinosis or history of elevated serum calcium
• Functional craniosynostosis
• Respiratory compromise or rachitic chest deformity
• Vitamin B6-responsive seizures
• Failure to thrive

3. Onset of symptoms prior to 6 months of age

4. Chronological age or adjusted age for premature infants born ≤ 37 weeks gestation of ≤ 5 years

5. Otherwise medically stable in the opinion of the Investigator and/or Sponsor

Exclusion Criteria

1. Clinically significant disease that precludes study participation, in the opinion of the Investigator and/or Sponsor

2. Serum calcium or phosphate levels below the normal range

3. Current evidence of treatable form of rickets

4. Prior treatment with bisphosphonates

5. Treatment with an investigational drug within 1 month prior to the start of asfotase alfa treatment

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

7. Intolerance to the investigational product (IP) or any of its excipients

8. Previous participation in the same study

9. Family relative of the Investigator

• Minimum Eligible Age: 1 Minute
• Maximum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Children's Hospital & Research Center Oakland

Oakland, California, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Lady Cilento Children's Hospital

South Brisbane, Queensland, Australia

Royal Children'S Hospital Melbourne

Parkville, Victoria, Australia

Health Sciences Centre Winnipeg, University of Manitoba

Winnipeg, Manitoba, Canada

Necker Hospital

Paris, , France

Chu de Toulouse

Toulouse, , France

Universitätskinderklinikum Würzburg

Würzburg, , Germany

Istituto Giannina Gaslini

Genova, , Italy

Ospedale Pediatrico Bambino Gesù

Roma, , Italy

Fukuoka Higashi Medical Hospital

Koga, Fukuoka, Japan

Ishikawa Prefectural Hospital

Kanazawa, Ishikawa-ken, Japan

St. Marianna University School of Medicine, Yokohayama City Seibu Hospital

Yokohama, Kanagawa, Japan

Tokyo Medical University Hospital

Shinjuku, Tokyo, Japan

Saitama Municipal Hospital

Saitama, , Japan

Federal State Budgetary Institution

Moscow, , Russia

King Faisal Specialist Hospital and Research Center

Riyadh, , Saudi Arabia

Hospital Infantil Universitario Nino Jesus

Madrid, , Spain

Uludag University

Bursa, , Turkey (Türkiye)

Birmingham Children's Hospital

Birmingham, , United Kingdom

Royal Manchester Children'S Hospital

Manchester, , United Kingdom

Sheffield Children'S Hospital

Sheffield, , United Kingdom

Countries

United States; Australia; Canada; France; Germany; Italy; Japan; Russia; Saudi Arabia; Spain; Turkey (Türkiye); United Kingdom

References

Padidela R, Yates R, Benscoter D, McPhail G, Chan E, Nichani J, Mughal MZ, Myer C 4th, Narayan O, Nissenbaum C, Wilkinson S, Zhou S, Saal HM. Characterization of tracheobronchomalacia in infants with hypophosphatasia. Orphanet J Rare Dis. 2020 Aug 6;15(1):204. doi: 10.1186/s13023-020-01483-9.

Reference Type: DERIVED

PMID: 32762706 (View on PubMed)

Hofmann CE, Harmatz P, Vockley J, Hogler W, Nakayama H, Bishop N, Martos-Moreno GA, Moseley S, Fujita KP, Liese J, Rockman-Greenberg C; ENB-010-10 Study Group. Efficacy and Safety of Asfotase Alfa in Infants and Young Children With Hypophosphatasia: A Phase 2 Open-Label Study. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2735-2747. doi: 10.1210/jc.2018-02335.

Reference Type: DERIVED

PMID: 30811537 (View on PubMed)

Whyte MP, Rockman-Greenberg C, Ozono K, Riese R, Moseley S, Melian A, Thompson DD, Bishop N, Hofmann C. Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia. J Clin Endocrinol Metab. 2016 Jan;101(1):334-42. doi: 10.1210/jc.2015-3462. Epub 2015 Nov 3.

Reference Type: DERIVED

PMID: 26529632 (View on PubMed)

Related Links

http://www.magicfoundation.org

HPP support group

http://www.softbones.org

US Hypophosphatasia Group (Soft Bones)

http://www.hypophosphatasia.com

Hypophosphatasia Website

http://www.hypophosphatasia.com/hcp/

Hypophosphatasia Website for Healthcare Providers

Other Identifiers

ENB-010-10

Identifier Type: -

Identifier Source: org_study_id