HypophosphatasiaPhase 4RESTORENCT06015750
Mitigate Immune-Mediated Loss of Therapeutic Response to Asfotase Alfa (STRENSIQ®) for Hypophosphatasia
A Phase 4 study testing methotrexate, rituximab and bortezomib in people with Hypophosphatasia, run by Alexion Pharmaceuticals, Inc..
Trial summary
The primary objective of this study is to evaluate the effect of immunosuppressive therapy (IST) in participants treated with asfotase alfa who demonstrate immune-mediated loss of effectiveness (LoE). Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Hypophosphatasia
- What is being tested?
- methotrexate, rituximab and bortezomib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 29 Jul 2026to 13 Mar 2030
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Reoccurrence or worsening of rickets for at least the past 3 months in participants who showed an initial efficacy response to asfotase alfa after at least 6 months of continuous treatment and currently receiving asfotase alfa. RSS will be used to determine severity at Baseline.
- Presence of ADAs, with or without NAbs, irrespective of their titers.
- Confirmation by the TMB that both the clinical evidence and immunogenicity-mediated association noted above are present.
- Female participants of childbearing potential and male participants with partners of childbearing potential must follow protocol-specified contraception guidance as described in Section 10.5.
- Participant, or participant's legal guardian, is capable of signing informed consent or assent as described in Section 10.1.3, which includes compliance with the requirements and restrictions listed in the informed consent or assent form and in this protocol.
Who cannot join
- Known history of human immunodeficiency virus (HIV) infection (evidenced by HIV type 1 or type 2 [HIV 1, HIV 2] antibody) or hepatitis B or C viral infection.
- Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to Screening.
- Inability of the participant, or the participant's legal guardian, to provide informed consent.
- Pregnant, breastfeeding, or intending to conceive during the course of the study.
- Inability to travel to the clinic for specified visits during the Treatment Period caused by disease per se or logistics (does not apply to external travel restrictions).
- The participant is at risk of reactivation or has an active significant viral infection such as hepatitis B, cytomegalovirus, herpes simplex, human polyomavirus (also known as John Cunningham [JC] virus), parvovirus, or Epstein Barr virus.
- The participant is at risk of reactivation of tuberculosis or has regular contact (eg, in the household) with individuals who are being actively treated for tuberculosis.
- The participant has had or is required to have any live vaccination within 1 month prior to enrollment.
About this study
Official title: An Interventional, Prospective Open-Label Study of Immunosuppressive Therapies to Mitigate Immune-Mediated Loss of Therapeutic Response to Asfotase Alfa (STRENSIQ®) for Hypophosphatasia (RESTORE)
The primary objective of this study is to evaluate the effect of immunosuppressive therapy (IST) in participants treated with asfotase alfa who demonstrate immune-mediated loss of effectiveness (LoE).
Read the detailed description
The administration of biological drugs to patients, especially for chronic conditions, carries a risk of eliciting anti-drug antibodies. Neutralizing antibodies can neutralize the clinical benefit of the agent. In postmarketing safety surveillance, some patients treated with asfotase alfa demonstrated an initial response, but subsequently recurrence and progression of disease. Consequently, the FDA requested a study to assess a potential serious risk of immune-mediated loss of effectiveness.
- Conditions
- Hypophosphatasia
- Being tested
- methotrexate, rituximab, bortezomib, IVIg, Folic Acid
- Keywords
- Hypophosphatasia, HPP, Asfotase alfa, Strensiq
- Medical subject headings
- Hypophosphatasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
methotrexateDrug
Methotrexate will be administered SC or orally weekly for 104 weeks.
rituximabDrug
Rituximab will be administered intravenously (IV) continuously weekly, for up to 74 weeks.
bortezomibDrug
Bortezomib will be administered via IV bolus or SC, as needed.
IVIgDrug
IVIg will be administered via IV monthly through initial 74 weeks.
Folic AcidDrug
Folic acid will be given orally as long as methotrexate is being dosed.
| Study group | Role | What they receive |
|---|---|---|
| Pediatric participants with HPP | Experimental | Pediatric participants who have been receiving asfotase alfa treatment for their HPP, and who demonstrate immune-mediated LoE. Receives: Drug: methotrexate; Drug: rituximab; Drug: bortezomib; Drug: IVIg; Drug: Folic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Achieve Immunosuppressive Therapy (IST) Complete Response at Week 100
Measured: Week 100
Secondary outcomes (6)
Number Participants with Antidrug Antibodies (ADAs) and Neutralizing Antibodies (NAbs)
Measured: Baseline Through Week 100
ADA and NAb Titer Levels
Measured: Baseline Through Week 100
Serum Concentration of Asofatase Alfa (Measured as Enzyme Activity)
Measured: Baseline Through Week 100
Plasma Concentration of Pyridoxal-5ˈ-Phosphate (PLP)
Measured: Baseline Through Week 100
Plasma Concentration of Inorganic Pyrophosphates (PPi)
Measured: Baseline Through Week 100
Number of Participants with Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events
Measured: Baseline Through Week 104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2023
- Study start29 Jul 2026 (estimated)
- Primary completion13 Mar 2030 (estimated)
- Study completion13 Mar 2030 (estimated)
Why it stopped: Sponsor decision following FDA release from the PMR.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 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
- NCT06015750
- Sponsor's protocol ID
- D8400C00001
- Other IDs
- AA-HPP-407, 2022-502793-17
- Acronym
- RESTORE
- Status last verified
- Oct 2025
- First submitted
- 23 Aug 2023
- Last updated
- 18 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Interventional, Prospective Open-Label Study of Immunosuppressive Therapies to Mitigate Immune-Mediated Loss of Therapeutic Response to Asfotase Alfa (STRENSIQ®) for Hypophosphatasia (RESTORE)
- ClinicalTrials.gov ID
- NCT06015750
- Acronym / sponsor ID
- RESTORE / D8400C00001
- Conditions
- Hypophosphatasia
- Keywords
- Hypophosphatasia, HPP, Asfotase alfa, Strensiq
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor decision following FDA release from the PMR.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 29 Jul 2026 (estimated)
- Primary completion
- 13 Mar 2030 (estimated)
- Study completion
- 13 Mar 2030 (estimated)
- First posted
- 29 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to evaluate the effect of immunosuppressive therapy (IST) in participants treated with asfotase alfa who demonstrate immune-mediated loss of effectiveness (LoE).
Detailed description
The administration of biological drugs to patients, especially for chronic conditions, carries a risk of eliciting anti-drug antibodies. Neutralizing antibodies can neutralize the clinical benefit of the agent. In postmarketing safety surveillance, some patients treated with asfotase alfa demonstrated an initial response, but subsequently recurrence and progression of disease. Consequently, the FDA requested a study to assess a potential serious risk of immune-mediated loss of effectiveness.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pediatric participants with HPP | Experimental | Drug: methotrexate, Drug: rituximab, Drug: bortezomib, Drug: IVIg, Drug: Folic AcidPediatric participants who have been receiving asfotase alfa treatment for their HPP, and who demonstrate immune-mediated LoE. |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Reoccurrence or worsening of rickets for at least the past 3 months in participants who showed an initial efficacy response to asfotase alfa after at least 6 months of continuous treatment and currently receiving asfotase alfa. RSS will be used to determine severity at Baseline.
- Presence of ADAs, with or without NAbs, irrespective of their titers.
- Confirmation by the TMB that both the clinical evidence and immunogenicity-mediated association noted above are present.
- Female participants of childbearing potential and male participants with partners of childbearing potential must follow protocol-specified contraception guidance as described in Section 10.5.
- Participant, or participant's legal guardian, is capable of signing informed consent or assent as described in Section 10.1.3, which includes compliance with the requirements and restrictions listed in the informed consent or assent form and in this protocol.
Key exclusion criteria (8 listed)
- Known history of human immunodeficiency virus (HIV) infection (evidenced by HIV type 1 or type 2 [HIV 1, HIV 2] antibody) or hepatitis B or C viral infection.
- Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to Screening.
- Inability of the participant, or the participant's legal guardian, to provide informed consent.
- Pregnant, breastfeeding, or intending to conceive during the course of the study.
- Inability to travel to the clinic for specified visits during the Treatment Period caused by disease per se or logistics (does not apply to external travel restrictions).
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 |
|---|---|---|
| methotrexateMethotrexate will be administered SC or orally weekly for 104 weeks. | Drug | Pediatric participants with HPP |
| rituximabRituximab will be administered intravenously (IV) continuously weekly, for up to 74 weeks. | Drug | Pediatric participants with HPP |
| bortezomibBortezomib will be administered via IV bolus or SC, as needed. | Drug | Pediatric participants with HPP |
| IVIgIVIg will be administered via IV monthly through initial 74 weeks. | Drug | Pediatric participants with HPP |
| Folic AcidFolic acid will be given orally as long as methotrexate is being dosed. | Drug | Pediatric participants with HPP |
Primary outcome
Number of Participants Who Achieve Immunosuppressive Therapy (IST) Complete Response at Week 100
Time frame: Week 100
6 secondary outcomes
Number Participants with Antidrug Antibodies (ADAs) and Neutralizing Antibodies (NAbs)
Time frame: Baseline Through Week 100
ADA and NAb Titer Levels
Time frame: Baseline Through Week 100
Serum Concentration of Asofatase Alfa (Measured as Enzyme Activity)
Time frame: Baseline Through Week 100
Plasma Concentration of Pyridoxal-5ˈ-Phosphate (PLP)
Time frame: Baseline Through Week 100
Plasma Concentration of Inorganic Pyrophosphates (PPi)
Time frame: Baseline Through Week 100
Number of Participants with Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events
Time frame: Baseline Through Week 104
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2025.
- Individual participant dataSharing planned: Yes. Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing methotrexate, rituximab and bortezomib in people with Hypophosphatasia, run by Alexion Pharmaceuticals, Inc..
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 5 inclusion and 8 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: withdrawn, as of the sponsor's last update on 18 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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 Who Achieve Immunosuppressive Therapy (IST) Complete Response at Week 100 (time frame: Week 100). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Dec 2025.