Pharmacokinetic and Dose Response Study of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia (HPP)

Alexion Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Hypophosphatasia

Treatments: Drug: Asfotase alfa

Study type: Interventional

Funder types: Industry

Identifiers

NCT02797821

AA-HPP-208

Details and patient eligibility

About

The purpose of this study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of asfotase alfa in adult participants with pediatric-onset HPP.

Enrollment: 27 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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27 participants in 3 patient groups

Asfotase Alfa 0.5 mg/kg Dose

Experimental group

Description:

Participants received 0.5 milligrams (mg) per kilogram (kg) of asfotase alfa administered subcutaneously (SC) 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.

Treatment:

Drug: Asfotase alfa

Asfotase Alfa 2.0 mg/kg Dose

Experimental group

Description:

Participants received 2.0 mg/kg of asfotase alfa administered SC 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.

Treatment:

Drug: Asfotase alfa

Asfotase Alfa 3.0 mg/kg Dose

Experimental group

Description:

Participants received 3.0 mg/kg of asfotase alfa administered SC 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.

Treatment:

Drug: Asfotase alfa