Immunosuppressive Therapy for Hypophosphatasia

(RESTORE Trial)

Recruiting at 4 trial locations

Overseen By Alexion Pharmaceuticals, Inc. (Sponsor)

Age: < 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Alexion Pharmaceuticals, Inc.

Must be taking: Asfotase alfa

Disqualifiers: HIV, Hepatitis B/C, Drug abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

8 Participants Needed

Trial Summary

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 safety data exists for immunosuppressive therapy in humans?

Immunosuppressive therapies, often used for conditions like Crohn's disease and ulcerative colitis, can have side effects ranging from mild to severe, including infections and increased risk of certain cancers. Some specific risks include pneumonia, tuberculosis, and rare types of lymphoma, especially when combined with other treatments. It's important to weigh these risks against the benefits and monitor for infections. ^{1 2 3 4 5}

How does immunosuppressive therapy differ from other treatments for hypophosphatasia?

Immunosuppressive therapy for hypophosphatasia is unique because it involves using drugs that suppress the immune system, which is not a standard approach for this condition. This therapy might be considered when other treatments are ineffective, as it targets the immune system to potentially reduce inflammation or other immune-related issues. ^{6 7 8 9 10}

What is the purpose of this trial?

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).

Eligibility Criteria

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.

Timeline

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

Treatment Details

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.

Participant Groups

Group I: Pediatric participants with HPP Experimental Treatment 5 Interventions

Pediatric participants who have been receiving asfotase alfa treatment for their HPP, and who demonstrate immune-mediated LoE.

Who Is Running the Clinical Trial?

Alexion Pharmaceuticals, Inc.

Lead Sponsor

Trials

267

Recruited

141,000+

Dr. Alberto R. Martinez

Alexion Pharmaceuticals, Inc.

Chief Medical Officer since 2010

MD from University of Sao Paulo

Marc Dunoyer

Alexion Pharmaceuticals, Inc.

Chief Executive Officer since 2021

PhD in Molecular Biology

Alexion

Lead Sponsor

Trials

247

Recruited

38,600+

Marc Dunoyer

Alexion

Chief Executive Officer since 2021

PhD in Molecular Biology, University of Brussels

Christophe Hotermans

Alexion

Chief Medical Officer since 2021

MD, University of Leuven

Findings from Research

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in IBD: to stop or continue immune suppressant and biologic treatment. McLean, LP., Cross, RK.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

The London position statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organisation: safety. [2011]

2. England pubmed.ncbi.nlm.nih.gov

Adverse events in IBD: to stop or continue immune suppressant and biologic treatment. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Infections in the Era of Targeted Therapies: Mapping the Road Ahead. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Thiopurine methyltransferase activity and the use of azathioprine in inflammatory bowel disease. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Infectious complications associated with monoclonal antibodies and related small molecules. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Burosumab in Pediatric Patients With X-Linked Hypophosphatemia: A Phase 3/4 Open-Label Trial. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Mycophenolate mofetil treatment in a patient with recurrent lymphocytic hypophysitis. [2020]

8. Japan pubmed.ncbi.nlm.nih.gov

Successful treatment of class IV+V lupus nephritis with combination therapy of high-dose corticosteroids, tacrolimus and intravenous cyclophosphamide. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Immune modulating therapy for IgA nephropathy: rationale and evidence. [2008]

10. Ukraine pubmed.ncbi.nlm.nih.gov

[Clinical aspects and treatment of primary focal segmental glomerulosclerosis and hyalinosis]. [2013]