pharmacokinetic and dose response study of asfotase alfa in adult patients with pediatric-onset hypophosphatasia (hpp)

Conditions: Hypophosphatasia

Summary: the purpose of this study was to evaluate the pharmacokinetics (pk) and pharmacodynamics (pd) of asfotase alfa in adult participants with pediatric-onset hpp.


Eligibility criteria:
inclusion criteria: 1. participants or their legal representative(s) provided written informed consent prior to undergoing any study-related procedures. 2. participants were ≥18 years of age at screening. 3. participant had pediatric-onset hypophosphatasia (hpp), defined as onset of first sign(s)/symptom (s) of hpp prior to 18 years of age. 4. participants had a documented diagnosis of hpp as indicated by a documented history of hpp-related skeletal abnormalities and 1 or more of the following: * documented tissue-nonspecific alkaline phosphatase (tnsalp) gene mutation(s) from a certified laboratory. * 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. 5. participants had a plasma inorganic pyrophosphate (ppi) level of ≥3.9 micromolar (µm) at screening. 6. female participants of childbearing potential had a negative pregnancy test at the time of enrollment. 7. sexually active male and female participants of childbearing potential agreed to use a highly effective method of birth control during the study. 8. female participants not of child-bearing potential due to 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. participants were willing to comply with study procedures and the visit schedule. exclusion criteria: 1. investigational site personnel directly affiliated with this study and/or their immediate families. immediate family was 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 non-approved use of a drug or device. 4. participated, within the last 30 days, in a clinical study involving a study drug (other than the study drug used in this study). 5. completed or withdrawn from this study or any other study investigating asfotase alfa in the previous 3 years. 6. women who were pregnant, planning to become pregnant, or breastfeeding. 7. serum 25-hydroxy vitamin d levels below 20 nanogram (ng) per milliliter (ml) at screening. 8. screening serum creatinine or parathyroid hormone (pth) levels ≥1.5 times the upper limit of normal. 9. any medical condition, serious concurrent illness and/or injury, recent orthopedic surgery, or other extenuating circumstance that, in the opinion of the investigator, may have significantly interfered with study compliance or study endpoints. 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 participants directly recorded data.

Keywords: hpp asfotase alfa