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

September 13, 2019 updated by: Alexion Pharmaceuticals

A Phase 2a, Randomized, Multicenter, Open-Label, Pharmacokinetic, and Dose Response Study of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Würzburg, Germany, 97074
        • University of Würzburg
  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Shriners Hospitals for Children
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt Medical Center Endocrinology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Asfotase Alfa 0.5 mg/kg Dose
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.
Drug: Asfotase alfa
Other Names:
  • Strensiq
Experimental: Asfotase Alfa 2.0 mg/kg Dose
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.
Drug: Asfotase alfa
Other Names:
  • Strensiq
Experimental: Asfotase Alfa 3.0 mg/kg Dose
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.
Drug: Asfotase alfa
Other Names:
  • Strensiq

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change In Plasma PPi From Baseline To Pre-3rd Dose At Week 9
Time Frame: Baseline to Week 9

Plasma PPi concentrations were determined using a specific enzyme-catalyzed reaction with a radiolabelled marker in a 3-step process. Baseline plasma PPi values were calculated by averaging pre-dose values from samples collected during the Run-in Period at -168, -156, -24, -12, and 0 hours before Baseline. Week 9 plasma PPi values were calculated using blood samples collected before administration of the 3rd dose. The analysis was a restricted maximum likelihood (REML)-based repeated measures mixed model with treatment, visit, sex, Baseline PPi, Baseline weight group (≥ median versus < median), and study drug lot assignment as factors, and an unstructured covariance structure for within-participant correlation.

Per inclusion criteria, participants had to have had a Screening PPi concentration of ≥3.9 micromolar (μM). Three participants (1 in each group) had Screening PPi concentrations of ≥3.9 μM, but Baseline PPi values ranged between 3.5 to 3.8 μM.
Baseline to Week 9

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change In Plasma PLP From Baseline To Pre-3rd Dose At Week 9
Time Frame: Baseline to Week 9
Plasma PLP was quantified using liquid chromatography/mass spectrometry. Baseline plasma PLP values were calculated by averaging the pre-dose PLP values from blood samples collected during the Run-in Period at -168, -156, -24, -12, and 0 hours before Baseline. Week 9 PLP values were calculated using blood samples collected before the administration of the 3rd dose. The analysis was a REML-based repeated measures mixed model with treatment, visit, sex, Baseline PPi, Baseline weight group (≥ median versus < median) and study drug lot assignment as factors, and an unstructured covariance structure for within-participant correlation.
Baseline to Week 9

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alexion Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 6, 2016

Primary Completion (Actual)

June 21, 2017

Study Completion (Actual)

June 21, 2017

Study Registration Dates

First Submitted

May 23, 2016

First Submitted That Met QC Criteria

June 8, 2016

First Posted (Estimate)

June 14, 2016

Study Record Updates

Last Update Posted (Actual)

September 17, 2019

Last Update Submitted That Met QC Criteria

September 13, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AA-HPP-208

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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