Immunosuppressive Therapy for Hypophosphatasia

(RESTORE Trial)

Not yet recruiting at 4 trial locations
AC
AP
AP
Overseen ByAlexion Pharmaceuticals, Inc. (Sponsor)
Age: < 65
Sex: Any
Trial Phase: Phase 4
Sponsor: Alexion Pharmaceuticals, Inc.
Must be taking: Asfotase alfa
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of immunosuppressive therapy for individuals with hypophosphatasia (HPP) who are already receiving asfotase alfa treatment but have experienced worsening due to immune reactions. The study aims to determine if adding this therapy can benefit those who initially responded well to asfotase alfa but now find it less effective. Ideal candidates have experienced a recurrence or worsening of rickets (a condition affecting bone development) for at least three months and have been on asfotase alfa for over six months. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand how it can benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the study involves immunosuppressive therapy, it's possible that some medications might need to be adjusted. Please consult with the trial coordinators for specific guidance.

What is the safety track record for immunosuppressive therapy?

Research has shown that asfotase alfa, a treatment for hypophosphatasia (HPP), is safe and effective. Patients who received asfotase alfa in studies experienced positive results over several years. These studies examined the long-term effects of the treatment in both adults and teenagers.

Regarding safety, researchers closely monitored any unwanted side effects and found no major safety issues. This indicates that asfotase alfa is generally well-tolerated by patients.

This trial tests the addition of immunosuppressive therapy for patients who have developed an immune reaction to asfotase alfa. The trial is in a later phase, which usually indicates strong safety support. While specific safety details for the immunosuppressive therapy in this context aren't provided, the advanced stage of the trial suggests that researchers have evaluated any risks and consider them manageable.12345

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatment for hypophosphatasia, which often involves enzyme replacement therapy like asfotase alfa, immunosuppressive therapy offers a fresh approach by potentially addressing immune-related complications. Researchers are excited about this therapy because it targets immune-mediated loss of efficacy, a challenge some patients face with current treatments. This approach could enhance the effectiveness of existing therapies, offering a new hope for patients with immune issues related to their hypophosphatasia treatment.

What evidence suggests that immunosuppressive therapy might be an effective treatment for hypophosphatasia?

Research shows that immunosuppressive therapy can help when the body's immune response reduces the effectiveness of asfotase alfa. Asfotase alfa improves bone health and growth in people with hypophosphatasia, but sometimes the immune system interferes with its effectiveness. Immunosuppressive therapy, which participants in this trial may receive, may calm the immune system, allowing asfotase alfa to continue working effectively. Previous studies have shown that asfotase alfa improves movement and quality of life for those with hypophosphatasia. This trial aims to determine if immunosuppressive therapy can assist when patients encounter difficulties with this treatment.16789

Are You a Good Fit for This Trial?

This trial is for people with Hypophosphatasia who initially responded to Asfotase Alfa treatment but are now seeing their condition worsen. They must have been on the treatment for at least 6 months and currently still be receiving it. Participants need proof of specific antibodies, agree to use contraception if they can have children, and sign a consent form.

Inclusion Criteria

My rickets got worse in the last 3 months despite taking asfotase alfa.
I am following the study's rules for birth control.
My tests show my cancer is likely to respond to immune therapy.
See 2 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive immunosuppressive therapy to mitigate immune-mediated loss of effectiveness to asfotase alfa

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Immunosuppressive Therapy
Trial Overview The study tests whether immunosuppressive therapy (IST) using drugs like methotrexate, rituximab, bortezomib, IVIg, and Folic Acid can help patients who've stopped responding well to Asfotase Alfa due to immune system interference.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Pediatric participants with HPPExperimental Treatment5 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Alexion Pharmaceuticals, Inc.

Lead Sponsor

Trials
267
Recruited
141,000+
Dr. Alberto R. Martinez profile image

Dr. Alberto R. Martinez

Alexion Pharmaceuticals, Inc.

Chief Medical Officer since 2010

MD from University of Sao Paulo

Marc Dunoyer profile image

Marc Dunoyer

Alexion Pharmaceuticals, Inc.

Chief Executive Officer since 2021

PhD in Molecular Biology

Alexion

Lead Sponsor

Trials
247
Recruited
38,600+
Marc Dunoyer profile image

Marc Dunoyer

Alexion

Chief Executive Officer since 2021

PhD in Molecular Biology, University of Brussels

Christophe Hotermans profile image

Christophe Hotermans

Alexion

Chief Medical Officer since 2021

MD, University of Leuven

Published Research Related to This Trial

Many patients with lupus nephritis do not respond to standard glucocorticoid treatments and may also be resistant to common immunosuppressive drugs like intravenous cyclophosphamide.
A case study demonstrated that adding tacrolimus to the treatment regimen of a patient with lupus nephritis unresponsive to cyclophosphamide led to successful outcomes, highlighting the potential benefits of multi-target therapy in managing this condition.
Successful treatment of class IV+V lupus nephritis with combination therapy of high-dose corticosteroids, tacrolimus and intravenous cyclophosphamide.Kurasawa, T., Nagasawa, H., Nishi, E., et al.[2019]
The review highlights that while treatments for Crohn's disease and ulcerative colitis, such as azathioprine, mercaptopurine, methotrexate, and biologic therapies, can be effective, they are associated with a range of adverse events, including serious complications like infections and malignancies.
It emphasizes the importance of gastroenterologists communicating the risks and benefits of these therapies to patients, and provides strategies for discussing when it may be appropriate to modify or discontinue treatment.
Adverse events in IBD: to stop or continue immune suppressant and biologic treatment.McLean, LP., Cross, RK.[2023]

Citations

Medical Management of Hypophosphatasia: Review ...A 12-months course of asfotase alfa resulted in healing of rickets at 6 months in 9 patients, accompanied by improvement in developmental ...
Enzyme replacement therapy for hypophosphatasia—The ...Growth was significantly improved after 18 months, and there were persisting benefits to parent-reported surveys of pain and disability. There ...
AM-PHARMA ANNOUNCES POSITIVE CLINICAL DATA ...The mean time to return to 90% of baseline was 9.3 hours in the low-dose cohort and 53 hours in the high-dose cohort. In addition, ilofotase ...
Challenges and Advances in Diagnosing and Treating ...Insights from the Global HPP Registry reveal significant disease burden and treatment gaps in treated and untreated adults. These insights ...
Effectiveness of asfotase alfa for treatment of adults with ...Adults with HPP who received asfotase alfa for ≥ 6 months experienced improvements in mobility, physical function, and HRQoL, which were maintained over 3 ...
6.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/39135540/
phase 1, dose-escalation study in adults with ...Our results showed that efzimfotase alfa has acceptable safety and pharmacokinetics and is effective for reducing biomarkers (measurable ...
Safety, pharmacokinetics, and pharmacodynamics of ...Five-year efficacy and safety of asfotase alfa therapy for adults and adolescents with hypophosphatasia ... hypophosphatasia: 7 year outcomes ...
A Prospective Sub-Study of the Global Hypophosphatasia ...An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...
125513Orig1s000 - accessdata.fda.gov... hypophosphatasia: transplantation therapy trial using bone fragments and ... The safety update also included preliminary top-line safety results from clinical ...
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