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

NCT02797821 | Completed Phase 2 Results

• 1 other identifier: AA-HPP-208
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 4

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.

Conditions

Hypophosphatasia

Keywords

HPP; asfotase alfa

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Change In Plasma PLP From Baseline To Pre-3rd Dose At Week 9

  Baseline to Week 9

Study Arms (3)

Asfotase Alfa 0.5 mg/kg Dose

EXPERIMENTAL

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

Asfotase Alfa 2.0 mg/kg Dose

EXPERIMENTAL

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

Asfotase Alfa 3.0 mg/kg Dose

EXPERIMENTAL

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

Interventions

Asfotase alfa DRUG

Also known as: Strensiq

Asfotase Alfa 0.5 mg/kg Dose; Asfotase Alfa 2.0 mg/kg Dose; Asfotase Alfa 3.0 mg/kg Dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants or their legal representative(s) provided written informed consent prior to undergoing any study-related procedures.
• Participants were ≥18 years of age at Screening.
• Participant had pediatric-onset hypophosphatasia (HPP), defined as onset of first sign(s)/symptom (s) of HPP prior to 18 years of age.
• 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.
• Participants had a plasma inorganic pyrophosphate (PPi) level of ≥3.9 micromolar (µM) at Screening.
• Female participants of childbearing potential had a negative pregnancy test at the time of enrollment.
• Sexually active male and female participants of childbearing potential agreed to use a highly effective method of birth control during the study.
• 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.
• Participants were willing to comply with study procedures and the visit schedule.

You may not qualify if:

• 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.
• Employees of Alexion Pharmaceuticals.
• Currently enrolled in a clinical study involving another study drug or non-approved use of a drug or device.
• Participated, within the last 30 days, in a clinical study involving a study drug (other than the study drug used in this study).
• Completed or withdrawn from this study or any other study investigating asfotase alfa in the previous 3 years.
• Women who were pregnant, planning to become pregnant, or breastfeeding.
• Serum 25-hydroxy Vitamin D levels below 20 nanogram (ng) per milliliter (mL) at Screening.
• Screening serum creatinine or parathyroid hormone (PTH) levels ≥1.5 times the upper limit of normal.
• 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.
• 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.
• Treatment with PTH, strontium, or sclerostin inhibitors within 6 months prior to the first dose of study drug.
• Unwilling or unable to comply with the use of a data collection device on which study participants directly recorded data.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (4)

Shriners Hospitals for Children

St Louis, Missouri, 63110, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Vanderbilt Medical Center Endocrinology

Nashville, Tennessee, 37232, United States

Location

University of Würzburg

Würzburg, 97074, Germany

Location

Related Publications (2)

• 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.

  PMID: 33822385 DERIVED

• 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.

  PMID: 32987199 DERIVED

Related Links

• HPP support group
• US Hypophosphatasia Group (Soft Bones)

MeSH Terms

Conditions

Hypophosphatasia

Interventions

asfotase alfa

Condition Hierarchy (Ancestors)

Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Alexion Pharmaceuticals
• Organization: Alexion Pharmaceuticals

ClinicalTrials@Alexion.com

475-230-2596

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2016
• First Posted: June 14, 2016
• Study Start: June 6, 2016
• Primary Completion: June 21, 2017
• Study Completion: June 21, 2017
• Last Updated: September 17, 2019
• Results First Posted: July 10, 2018

Record last verified: 2019-09

Locations

US (3); DE (1)