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

Hypophosphatasia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02797821
• Other study ID #: AA-HPP-208
• Status: Completed
• Phase: Phase 2
• Start date: June 6, 2016
• Est. completion date: June 21, 2017

Study information

• Verified date: September 2019
• Source: Alexion Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: June 21, 2017
• Est. primary completion date: June 21, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hypophosphatasia

Intervention

Drug:
• Asfotase alfa

Locations

Country	Name	City	State
Germany	University of Würzburg	Würzburg
United States	Duke University Medical Center	Durham	North Carolina
United States	Vanderbilt Medical Center Endocrinology	Nashville	Tennessee
United States	Shriners Hospitals for Children	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change In Plasma PPi From Baseline To Pre-3rd Dose At 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	Change In Plasma PLP From Baseline To Pre-3rd Dose At 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

External Links

•   HPP support group
•   Hypophosphatasie Europe
•   US Hypophosphatasia Group (Soft Bones)
•   Yahoo health group for HPP with an international list serve where participants can correspond and post questions to the group