Hypophosphatasia is a rare inborn error of bone metabolism caused by inactivating mutations in the gene encoding the Tissue-nonspecific alkaline phosphatase isoenzyme. With deficiency of Tissue-nonspecific alkaline phosphatase, there is a buildup of extracellular inorganic pyrophosphate, which inhibits mineralization of bone matrix. MedDRA version: 20.0 Level: PT Classification code 10049933 Term: Hypophosphatasia System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Alexion Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet all of the following criteria for enrollment in this study: 1. Patients or their legal representative(s) must provide written informed consent prior to undergoing any study-related procedures 2. Patient has pediatric-onset HPP, defined as onset of first sign(s)/symptom(s) of HPP prior to 18 years of age 3. Documented diagnosis of HPP as indicated by a documented history of HPP-related skeletal abnormalities and 1 or more of the following: - Documented TNSALP gene mutation(s) from a certified laboratory - Serum ALP level below the age-adjusted normal range AND plasma PLP above the upper limit of normal at Screening. 4. Patients must have a plasma PPi level of =3.9 µM at Screening 5. Patients must be =18 years of age at Screening 6. Sexually active male and female patients of childbearing potential must agree to use a highly effective method of birth control during the study and for 3 months following the last dose of study drug. Male patients must also not donate sperm during the Screening and treatment periods and for at least 3 months after the last dose of asfotase alfa. Highly effective contraceptive methods are as follows: a. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation- Oral b. Progestogen-only hormonal contraception associated with inhibition of ovulation- Oral c. Intrauterine device d. Intrauterine hormone-releasing system e. Bilateral tubal occlusion f. Vasectomy with documented medical assessment of surgical success g. Condom and spermicide 7. Female patients of childbearing potential must have a negative pregnancy test at the time of enrollment 8. Female patients not of child-bearing potential due to surgical sterilization (at least 6 weeks after surgical bilateral oophorectomy with or without hysterectomy or at least 6 weeks after tubal ligation) confirmed by medical history, or menopause 9. Patients must be willing to comply with study procedures and the visit schedule Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 36 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients will be excluded from participation in this study if they meet any of the following exclusion criteria: 1. Investigational site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. 2. Employees of Alexion Pharmaceuticals 3. Currently enrolled in a clinical study involving another study drug or nonapproved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study (excluding the HPP registry, in which concurrent enrollment is allowed). 4. Participated, within the last 30 days, in a clinical study involving a study drug (other than the study drug used in this study). If the previous study drug has a long half-life, 3 months or 5 half-lives (whichever is longer) should have passed. 5. Have completed or withdrawn from this study or any other study investigating asfotase alfa in the previous 3 years. This exclusion criterion does not apply to patients who are re-screened prior to randomization or patients enrolled in the HPP registry. 6. Women who are pregnant, planning to become pregnant, or breastfeeding 7. Serum 25-OH Vitamin D below 20 ng/mL at Screening 8. Screening serum creatinine or parathyroid hormone (PTH) levels 1.5 times the upper limit of normal 9. Medical condition, serious concurrent illness and/or injury, recent orthopedic surgery, or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study compliance or study endpoints, including all prescribed evaluations and follow-up activities 10. Prior treatment with bisphosphonates within 2 years of study entry for any length of time or for more than 2 consecutive years at any prior timepoint 11. Treatment with PTH, strontium, or sclerostin inhibitors within 6 months prior to the first dose of study drug 12. Unwilling or unable to comply with the use of a data collection device on which study patients will directly record data
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of asfotase alfa following administration of a range of dose regimens that encompasses the dose proven to be effective in children ( in adult patients with pediatric-onset HPP.;Secondary Objective: to evaluate the safety and tolerability of asfotase alfa in adult patients with pediatric-onset HPP;Primary end point(s): Change in PPi;Timepoint(s) of evaluation of this end point: Week -12 to -2, -1, 1, 2, 3-5, 7-8, 9, 10-12, 13 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change of PLP, assessment of PK parameters and assessment of safety;Timepoint(s) of evaluation of this end point: Change of PLP: Week -12 to -2, -1, 1, 2, 3-5, 7-8, 9, 10-12, 13 PK parameters: Week 1, 2, 3-5, 7-8, 9, 10-12, 13 Safety: study duration | — |
Countries
Germany, United States
Contacts
Public ContactEuropean Clinical Trial Information
Alexion Europe SAS
Outcome results
None listed