HypophosphatasiaPhase 2NCT02797821
Pharmacokinetic and Dose Response Study of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia (HPP)
A Phase 2 study testing Asfotase alfa in people with Hypophosphatasia, run by Alexion Pharmaceuticals, Inc. at 4 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypophosphatasia
- What is being tested?
- Asfotase alfa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 6 Jun 2016to 21 Jun 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United States3 sites
Duke University Medical Center
Durham, North Carolina, 27710
Vanderbilt Medical Center Endocrinology
Nashville, Tennessee, 37232
Shriners Hospitals for Children
St Louis, Missouri, 63110
About this study
Official title: 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.
- Conditions
- Hypophosphatasia
- Being tested
- Asfotase alfa
- Keywords
- HPP, asfotase alfa
- Medical subject headings
- Hypophosphatasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Asfotase alfaDrug
Also called Strensiq
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Asfotase alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Week 9
Secondary outcomes (1)
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.
Measured: Baseline to Week 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2016 (estimated)
- Study start6 Jun 2016
- Primary completion21 Jun 2017
- Study completion21 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HypophosphatasiaStudies of the same condition, open and under way.
- More trials run by Alexion Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02797821
- Sponsor's protocol ID
- AA-HPP-208
- Status last verified
- Sep 2019
- First submitted
- 23 May 2016
- Last updated
- 17 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 33822385Seefried 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.
PubMed 32987199
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a, Randomized, Multicenter, Open-Label, Pharmacokinetic, and Dose Response Study of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia
- ClinicalTrials.gov ID
- NCT02797821
- Acronym / sponsor ID
- AA-HPP-208
- Conditions
- Hypophosphatasia
- Keywords
- HPP, asfotase alfa
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 6 Jun 2016 (actual)
- Primary completion
- 21 Jun 2017 (actual)
- Study completion
- 21 Jun 2017 (actual)
- First posted
- 14 Jun 2016 (estimated)
- Results
- Posted 10 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Asfotase Alfa 0.5 mg/kg Dose | Experimental | Drug: Asfotase alfaParticipants 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. |
| Asfotase Alfa 2.0 mg/kg Dose | Experimental | Drug: Asfotase alfaParticipants 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. |
| Asfotase Alfa 3.0 mg/kg Dose | Experimental | Drug: Asfotase alfaParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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:
- Participants had a plasma inorganic pyrophosphate (PPi) level of ≥3.9 micromolar (µM) at Screening.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Asfotase alfaAlso: Strensiq | Drug | Asfotase Alfa 0.5 mg/kg Dose, Asfotase Alfa 2.0 mg/kg Dose, Asfotase Alfa 3.0 mg/kg Dose |
Primary outcome
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.
1 secondary outcome
Change In Plasma PLP From Baseline To Pre-3rd Dose At Week 9
Time frame: Baseline to Week 9
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33822385Pan 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.
- Derived from this study: PubMed 32987199Seefried 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.
- HPP support groupLink provided by the sponsor.
- US Hypophosphatasia Group (Soft Bones)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Asfotase alfa in people with Hypophosphatasia, run by Alexion Pharmaceuticals, Inc. at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change In Plasma PPi From Baseline To Pre-3rd Dose At Week 9 (time frame: Baseline to Week 9). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02797821, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2019.