HypophosphatasiaPhase 1NCT04980248
Study of ALXN1850 in Participants With Hypophosphatasia (HPP)
A Phase 1 study testing ALXN1850 in people with Hypophosphatasia, run by Alexion Pharmaceuticals, Inc. at 4 sites in United States.
Trial summary
This is an open-label, dose-escalating study to assess safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and immunogenicity of ALXN1850 when given intravenous (IV) and subcutaneous (SC) to adults with HPP. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Hypophosphatasia
- What is being tested?
- ALXN1850
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 4 sitesUnited States
- Study dates
- 28 Sep 2021to 24 Aug 2022
- Phase
- Phase 1
- 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 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Confirmed clinical diagnosis of HPP
- Not anticipated to require further treatment with enzyme replacement therapy to treat participant's HPP after study completion
- Willing and able to follow protocol-specified contraception requirements
- Willing and able to give informed consent
Who cannot join
- Primary or secondary hyperparathyroidism or hypoparathyroidism
- Fracture within 12 weeks of screening
- Current or relevant history of unstable physical or psychiatric illness
- Significant allergies
- Asfotase alfa use within 6 months and/or positive for asfotase alfa antidrug antibody/neutralizing antibodies
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Research Site
Austin, Texas, 78744
Research Site
Columbus, Ohio, 43203
Research Site
Las Vegas, Nevada, 89113
Research Site
Nashville, Tennessee, 37232
About this study
Official title: A Phase 1, Open-label, Dose-escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ALXN1850 in Adults With Hypophosphatasia
This is an open-label, dose-escalating study to assess safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and immunogenicity of ALXN1850 when given intravenous (IV) and subcutaneous (SC) to adults with HPP.
- Conditions
- Hypophosphatasia
- Being tested
- ALXN1850
- Keywords
- HPP, enzyme replacement therapy, low alkaline phosphatase, tissue-nonspecific alkaline phosphatase, TNSALP
- Medical subject headings
- Hypophosphatasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALXN1850Biological
ALXN1850 will be administered as an IV infusion and via the SC route.
| Study group | Role | What they receive |
|---|---|---|
| ALXN1850 | Experimental | Three experimental cohorts will be administered 3 dosages (low, medium, high) of ALXN1850, respectively, via IV infusion and/or SC over multiple administration intervals. Receives: Biological: ALXN1850 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
TEAEs were defined as any adverse events (AEs) that began or worsened on or after the first dose of treatment until the final follow-up visit. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. TESAEs were defined as any serious AEs that began or worsened on or after the first dose of treatment until the final follow-up visit. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Measured: Day 1 up to Day 85
Secondary outcomes (11)
Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3
Measured: Predose, 2, 6 and 12 hours postdose on Days 1, 15, 22 and 29
Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity Following IV Dose of ALXN1850
Measured: Predose, 2, 6 and 12 hours postdose on Days 1, 15, 22 and 29
Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Following SC Dose 1, SC Dose 2 and SC Dose 3
Measured: Predose, 2, 6 and 12 hour postdose on Days 1, 15, 22 and 29
Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Values of the First SC Versus IV Administration of ALXN1850
Measured: Predose, 2, 6 and 12 hour postdose on Days 1, 15, 22 and 29
Absolute Change From Baseline in Plasma Concentration of Pyridoxal-5' Phosphate (PLP) at Week 1
Measured: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Absolute Change From Baseline in Plasma Concentration of Inorganic Pyrophosphate (PPi) at Week 1
Measured: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Absolute Change From Baseline in Plasma Concentration of Pyridoxal Phosphate/ Pyridoxal (PLP/PL) Ratio at Week 1
Measured: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Percent Change From Baseline in Plasma Concentration of PLP at Week 1
Measured: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Percent Change From Baseline in Plasma Concentration of PPi at Week 1
Measured: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Percent Change From Baseline in Plasma Concentration of PLP/PL Ratio Over Time at Week 1
Measured: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Number of Participants With Anti-drug Antibody (ADA) Positive and Neutralizing Antibody (NAb) Positive Status
Measured: Baseline up to Day 85
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2021
- Study start28 Sep 2021
- Primary completion24 Aug 2022
- Study completion24 Aug 2022
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 (1)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 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Study participants will be enrolled into 3 cohorts in a sequential fashion.
- Masking
- None (open label)
- Enrolment
- 15 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
- NCT04980248
- Sponsor's protocol ID
- ALXN1850-HPP-101
- Status last verified
- Nov 2024
- First submitted
- 23 Jul 2021
- Last updated
- 27 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Dahir KM, Shannon A, Dunn D, Voegtli W, Dong Q, Hasan J, Pradhan R, Pelto R, Pan WJ. Safety, pharmacokinetics, and pharmacodynamics of efzimfotase alfa, a second-generation enzyme replacement therapy: phase 1, dose-escalation study in adults with hypophosphatasia. J Bone Miner Res. 2024 Sep 26;39(10):1412-1423. doi: 10.1093/jbmr/zjae128.
PubMed 39135540
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, Dose-escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ALXN1850 in Adults With Hypophosphatasia
- ClinicalTrials.gov ID
- NCT04980248
- Acronym / sponsor ID
- ALXN1850-HPP-101
- Conditions
- Hypophosphatasia
- Keywords
- HPP, enzyme replacement therapy, low alkaline phosphatase, tissue-nonspecific alkaline phosphatase, TNSALP
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 28 Sep 2021 (actual)
- Primary completion
- 24 Aug 2022 (actual)
- Study completion
- 24 Aug 2022 (actual)
- First posted
- 28 Jul 2021 (actual)
- Results
- Posted 27 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, dose-escalating study to assess safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and immunogenicity of ALXN1850 when given intravenous (IV) and subcutaneous (SC) to adults with HPP.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Study participants will be enrolled into 3 cohorts in a sequential fashion.
| Arm | Type | Receives |
|---|---|---|
| ALXN1850 | Experimental | Biological: ALXN1850Three experimental cohorts will be administered 3 dosages (low, medium, high) of ALXN1850, respectively, via IV infusion and/or SC over multiple administration intervals. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Confirmed clinical diagnosis of HPP
- Not anticipated to require further treatment with enzyme replacement therapy to treat participant's HPP after study completion
- Willing and able to follow protocol-specified contraception requirements
- Willing and able to give informed consent
Key exclusion criteria (5 listed)
- Primary or secondary hyperparathyroidism or hypoparathyroidism
- Fracture within 12 weeks of screening
- Current or relevant history of unstable physical or psychiatric illness
- Significant allergies
- Asfotase alfa use within 6 months and/or positive for asfotase alfa antidrug antibody/neutralizing antibodies
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 |
|---|---|---|
| ALXN1850ALXN1850 will be administered as an IV infusion and via the SC route. | Biological | ALXN1850 |
Primary outcome
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Time frame: Day 1 up to Day 85
TEAEs were defined as any adverse events (AEs) that began or worsened on or after the first dose of treatment until the final follow-up visit. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. TESAEs were defined as any serious AEs that began or worsened on or after the first dose of treatment until the final follow-up visit. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
11 secondary outcomes
Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3
Time frame: Predose, 2, 6 and 12 hours postdose on Days 1, 15, 22 and 29
Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity Following IV Dose of ALXN1850
Time frame: Predose, 2, 6 and 12 hours postdose on Days 1, 15, 22 and 29
Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Following SC Dose 1, SC Dose 2 and SC Dose 3
Time frame: Predose, 2, 6 and 12 hour postdose on Days 1, 15, 22 and 29
Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Values of the First SC Versus IV Administration of ALXN1850
Time frame: Predose, 2, 6 and 12 hour postdose on Days 1, 15, 22 and 29
Absolute Change From Baseline in Plasma Concentration of Pyridoxal-5' Phosphate (PLP) at Week 1
Time frame: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Absolute Change From Baseline in Plasma Concentration of Inorganic Pyrophosphate (PPi) at Week 1
Time frame: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Absolute Change From Baseline in Plasma Concentration of Pyridoxal Phosphate/ Pyridoxal (PLP/PL) Ratio at Week 1
Time frame: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Percent Change From Baseline in Plasma Concentration of PLP at Week 1
Time frame: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Percent Change From Baseline in Plasma Concentration of PPi at Week 1
Time frame: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Percent Change From Baseline in Plasma Concentration of PLP/PL Ratio Over Time at Week 1
Time frame: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Number of Participants With Anti-drug Antibody (ADA) Positive and Neutralizing Antibody (NAb) Positive Status
Time frame: Baseline up to Day 85
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39135540Dahir KM, Shannon A, Dunn D, Voegtli W, Dong Q, Hasan J, Pradhan R, Pelto R, Pan WJ. Safety, pharmacokinetics, and pharmacodynamics of efzimfotase alfa, a second-generation enzyme replacement therapy: phase 1, dose-escalation study in adults with hypophosphatasia. J Bone Miner Res. 2024 Sep 26;39(10):1412-1423. doi: 10.1093/jbmr/zjae128.
- Related InfoLink provided by the sponsor.
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Hypophosphatasia
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 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ALXN1850 in people with Hypophosphatasia, run by Alexion Pharmaceuticals, Inc. at 4 sites in United States.
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 4 inclusion and 5 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 27 Dec 2024. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 27 Dec 2024). 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?
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) (time frame: Day 1 up to Day 85). 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 NCT04980248, which also lists 1 linked publication.
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 27 Dec 2024.