Expanded Access Program for Asfotase Alfa Treatment for Patients With Infantile- or Juvenile-onset Hypophosphatasia (HPP)

NCT02496689 | Unknown

• 1 other identifier: AA-HPP-405
• Study Type: expanded_access
• Target: N/A
• Locations: 2 countries
• Sites: 5

Brief Summary

This clinical trial is being conducted in Hypophosphatasia, a bone disorder caused by gene mutation(s) resulting in bone defects. These gene mutations cause low levels of an enzyme needed to harden bone. The purpose of this study is to provide access to treatment in a disease where no approved treatment exists. This is an experimental treatment provided under specific treatment guidelines in which safety endpoints will be collected.

Conditions

Hypophosphatasia

Keywords

HPP; Bone Disease; Soft Bones; Low Alkaline Phosphatase; genetic metabolic disorder; alkaline phosphatase; rickets; osteomalacia

Interventions

asfotase alfa BIOLOGICAL

Patients participating in this program will receive 6 mg/kg/week asfotase alfa (administered at a dosage regimen of 1 mg/kg 6 times per week or 2 mg/kg 3 times per week at the discretion of the Investigator) by SC injection. During follow-up visits, dose adjustments to account for changes in body weight will be made. Additional incremental dose adjustments for lack of efficacy or safety reasons may also be decided upon by the Investigator in consultation with the Alexion Medical Monitor.

Eligibility Criteria

• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient or parent (or legal guardian) must provide written informed consent prior to the performance of any program-related procedures and must be willing to comply with program procedures. Where appropriate and required by local regulations, patient assent for participation must also be obtained.
• Patient must have a documented diagnosis of HPP as indicated by a documented history of HPP-related skeletal abnormalities and one or more of the following:
• Documented tissue-nonspecific alkaline phosphatase (TNSALP) gene mutation(s)
• Serum alkaline phosphatase (ALP) level below the age-adjusted normal range AND plasma pyridoxal-5'-phosphate (PLP) above the upper limit of normal at Screening. NOTE: Historical results for PLP may be used to determine patient eligibility. The criterion for plasma PLP is not applicable if the patient is receiving pyridoxine treatment.
• Patient must have infantile- or juvenile-onset HPP, defined as documented onset of signs/symptoms of HPP prior to 18 years of age.
• Male patient is:
• Prepubertal; OR
• Surgically sterile (defined as vasectomized for ≥6 months at Baseline); OR
• Non-surgically sterile (defined as non-vasectomized or vasectomized for \<6 months at Baseline) and his female spouse/partner who is of childbearing potential must be using highly effective contraception consisting of two forms of birth control (at least one of which must be a barrier method) as described below starting at Baseline and continuing for 3 months after program completion.
• Simultaneous use of condom, and for the female partner established use of hormonal contraceptives (eg, oral, injected, implanted) or intra-uterine contraceptive device
• Simultaneous use of condom, and for the female partner occlusive cap (diaphragm or cervical/vault caps) with intravaginally applied spermicide
• Female patient is:
• Of non-childbearing potential, defined as:
• Prepubertal; OR
• Post-menopausal (defined as absence of menses for 12 months prior to Baseline or bilateral oophorectomy or hysterectomy with bilateral oophorectomy at least 6 months prior to Baseline); OR

You may not qualify if:

• Patient has geographic access to and qualifies for enrollment (as determined by the Sponsor and Investigator) in any other Alexion-sponsored clinical trials of asfotase alfa that are open to enrollment (eg, ENB-010-10).
• Patient is pregnant, trying to become pregnant, or is lactating.
• Patient has a documented sensitivity to any of the components of asfotase alfa.
• Patient has serum calcium and/or phosphorus levels below the normal range at Screening.
• Patient is currently enrolled in any other program or study involving an investigational new drug, device, or treatment for HPP (eg, bone marrow transplantation).
• Patient has any other medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with program compliance, including all evaluations and follow-up activities. Patients who previously received treatment with asfotase alfa may be considered for enrollment.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (5)

Colorado Center for Bone Research

Lakewood, Colorado, 80227, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Hôpital Bicêtre

Le Kremlin-Bicêtre, 94275, France

Location

Hôpital Necker - Enfants Malades

Paris, 75015, France

Location

Hôpital des Enfants

Toulouse, 31259, France

Location

MeSH Terms

Conditions

Hypophosphatasia; Bone Diseases; Rickets; Osteomalacia

Interventions

asfotase alfa

Condition Hierarchy (Ancestors)

Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases, Metabolic; Calcium Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders

Study Officials

• Andrew Denker, MD, PhD

  Medical Monitor

  STUDY DIRECTOR

Study Design

• Study Type: expanded access
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2015
• First Posted: July 14, 2015
• Last Updated: March 29, 2019

Record last verified: 2019-03

Locations

US (2); FR (3)