Pharmacokinetic and Dose Response Study of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia (HPP)
Condition: Hypophosphatasia
MeSH terms: Hypophosphatasia
Intervention: Asfotase alfa
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HPP; asfotase alfa

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.