Clinical trial NCT02797821: Pharmacokinetic and Dose Response Study of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia (HPP)
Official title: A Phase 2a, Randomized, Multicenter, Open-Label, Pharmacokinetic, and Dose Response Study of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypophosphatasia
Keywords: HPP
asfotase alfa
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2016-06-14
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Change In Plasma PPi From Baseline To Pre-3rd Dose At Week 9
timeFrame: Baseline to Week 9
Secondary outcomes:
measure: Change In Plasma PLP From Baseline To Pre-3rd Dose At Week 9
timeFrame: Baseline to Week 9
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Shriners Hospitals for Children
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Nashville
country: United States
facility: Vanderbilt Medical Center Endocrinology
state: Tennessee
city: Würzburg
country: Germany
facility: University of Würzburg
Study officials:
References:
citation: Pan WJ, Pradhan R, Pelto R, Seefried L. Pharmacokinetics of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia. J Clin Pharmacol. 2021 Oct;61(10):1334-1343. doi: 10.1002/jcph.1870. Epub 2021 Jun 19.
citation: Seefried L, Kishnani PS, Moseley S, Denker AE, Watsky E, Whyte MP, Dahir KM. Pharmacodynamics of asfotase alfa in adults with pediatric-onset hypophosphatasia. Bone. 2021 Jan;142:115664. doi: 10.1016/j.bone.2020.115664. Epub 2020 Sep 26.