ALXN1850 for Hypophosphatasia

(CHESTNUT Trial)

Not currently recruiting at 30 trial locations

Overseen By Alexion Pharmaceuticals, Inc. (Sponsor)

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Alexion Pharmaceuticals, Inc.

Must be taking: Asfotase alfa

Disqualifiers: Cardiovascular, Respiratory, Hepatic, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 9

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, ALXN1850, for children with hypophosphatasia (HPP), a rare bone condition. Researchers aim to determine the safety of ALXN1850 and compare it to the current treatment, asfotase alfa. The trial includes two groups: one receiving ALXN1850 and the other receiving asfotase alfa. Children who have been on asfotase alfa for at least six months and still have open growth plates in their bones may qualify for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment for HPP.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must have been on a specific dose of asfotase alfa for at least 6 months before starting the trial.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must have been on a specific dose of asfotase alfa for at least 6 months before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study tested ALXN1850, also known as efzimfotase alfa, in adults and found it to be generally safe. Participants tolerated the treatment well, with no major safety concerns reported. This newer enzyme replacement therapy aids in treating hypophosphatasia (HPP), a rare bone disorder.

Asfotase alfa, an existing treatment for HPP, has improved symptoms like bone and breathing problems. Most patients tolerate it well, with only a few serious side effects reported. It has been studied for over seven years, demonstrating a strong safety record.

For those considering joining a clinical trial, these findings offer reassurance about the safety of both ALXN1850 and asfotase alfa in treating HPP. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ALXN1850 for hypophosphatasia because, unlike the current treatment asfotase alfa, it offers a potentially more convenient dosing schedule. ALXN1850 is administered once every two weeks, compared to asfotase alfa's multiple weekly injections. This could significantly improve patient comfort and adherence to the treatment plan. Both options target the underlying enzyme deficiency, but ALXN1850 could make managing the condition easier for patients.

What evidence suggests that this trial's treatments could be effective for hypophosphatasia?

Research has shown that asfotase alfa, one of the treatments in this trial, effectively treats hypophosphatasia (HPP). Adults with HPP who received asfotase alfa experienced better movement, improved physical abilities, and enhanced quality of life. These improvements lasted for several years, indicating long-term benefits.

ALXN1850, also known as efzimfotase alfa, is another treatment option in this trial. It replaces the missing enzyme that helps the body use phosphate to build bones. Early studies suggest it can lower certain blood indicators, pointing to its potential effectiveness for HPP. Although still under investigation, its mechanism suggests it could be a promising option. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for children with Hypophosphatasia (HPP) who are in early puberty or younger, have open growth plates, and have been treated with asfotase alfa for at least 6 months. They must weigh over 10 kg and not have had a new fracture recently. Kids can't join if they've had certain other health problems or surgeries that might affect the study, or if they're allergic to ingredients in the treatments.

Inclusion Criteria

My medical records show a diagnosis of HPP.

Your bones are still growing, as shown in an X-ray.

My physical development is at or before early puberty.

Exclusion Criteria

I am not allergic to asfotase alfa or ALXN1850.

I have not had any new fractures in the last 12 weeks.

I do not have any major health issues that could affect how my body handles medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ALXN1850 or asfotase alfa for a total of 24 weeks

24 weeks

Frequent visits during the treatment period

Open-label extension (Part A)

Participants continue treatment with frequent visits over the first 24 weeks

24 weeks

Frequent visits

Open-label extension (Part B)

Participants have visits every 9 months for up to approximately 108 weeks

108 weeks

Visits every 9 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ALXN1850
• asfotase alfa

Trial Overview The trial is testing ALXN1850 against asfotase alfa to see which one is safer and more tolerable for kids with HPP who've already tried asfotase alfa. It's a Phase 3 study where participants will be randomly assigned to receive either ALXN1850 or continue their current treatment of asfotase alfa.

How Is the Trial Designed?

Group I: asfotase alfa Experimental Treatment 1 Intervention

Starting at Day 1 of the Randomized Evaluation Period, participants will receive asfotase alfa for a total of 24 weeks. Participants will receive 6 mg/kg/week of asfotase alfa via SC injection as either 2 mg/kg 3 times per week or 1 mg/kg 6 times per week. Part A of the OLE Period participants will have frequent visits over the first 24 weeks; Part B will have visits every 9 months for up to approximately 108 weeks.

Group II: ALXN1850 Experimental Treatment 2 Interventions

Starting at Day 1 of the Randomized Evaluation Period participants will receive ALXN1850 for a total of 24 weeks. Participants will receive bodyweight dependent doses of either 20mg, 35mg or 50mg of ALXN1850 once q2w via SC injection. During Part A of the OLE Period, participants will have frequent visits over the first 24 weeks; Part B of the OLE Period participants will have visits every 9 months for up to approximately 108 weeks.

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

Published Research Related to This Trial

Asfotase alfa (Strensiq(®)) is a first-in-class therapy that effectively treats bone manifestations of hypophosphatasia (HPP) in pediatric patients, showing significant improvements in bone mineralization and rickets severity within 24 weeks, with benefits sustained for over 3 years.

In addition to enhancing bone health, asfotase alfa has been associated with improved respiratory function, motor skills, cognitive development, and overall survival in severe cases of HPP, while being generally well tolerated with few serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asfotase Alfa: A Review in Paediatric-Onset Hypophosphatasia. Scott, LJ.[2022]

Asfotase alfa, an enzyme replacement therapy for hypophosphatasia, showed significant long-term benefits in 6 adults over 61-68 months, but clinical deterioration occurred after treatment was discontinued for 15-48 months.

Upon restarting asfotase alfa, patients demonstrated improvement, highlighting the need for close monitoring and clinical practice guidelines for managing treatment interruptions in hypophosphatasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of discontinuing 5 years of enzyme replacement treatment in a cohort of 6 adults with hypophosphatasia: A case series. Rockman-Greenberg, C., Josse, R., Francis, M., et al.[2022]

In a study involving 19 adults and adolescents with hypophosphatasia (HPP), treatment with asfotase alfa significantly increased levels of pyridoxal 5'-phosphate (PLP) after 6 months, indicating its efficacy in normalizing TNSALP substrate levels.

Patients treated with asfotase alfa showed improvements in functional abilities, such as increased walking distance over 5 years, and the treatment was generally well tolerated with mild to moderate side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year efficacy and safety of asfotase alfa therapy for adults and adolescents with hypophosphatasia. Kishnani, PS., Rockman-Greenberg, C., Rauch, F., et al.[2020]

Asfotase alfa (Strensiq™) is an effective treatment for perinatal/infantile and juvenile-onset hypophosphatasia (HPP), showing positive results in clinical trials lasting up to 5 years.

Patients treated with asfotase alfa experienced significantly improved survival and ventilation-free survival compared to untreated historical controls, linked to enhanced bone mineralization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asfotase Alfa in Perinatal/Infantile-Onset and Juvenile-Onset Hypophosphatasia: A Guide to Its Use in the USA. Scott, LJ.[2022]

Asfotase alfa, the only approved treatment for pediatric-onset hypophosphatasia, can interfere with certain immunoassays that utilize alkaline phosphatase (ALP), potentially leading to false positive or negative results in blood tests.

While asfotase alfa was detected in most ALP assays, it did not affect tests using alternative detection systems, and its interference could be eliminated through sample extraction, highlighting the importance of testing assays for this interference in treated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interference of Asfotase Alfa in Immunoassays Employing Alkaline Phosphatase Technology. Piec, ID., Tompkins, B., Fraser, WD.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11425692/

Safety, pharmacokinetics, and pharmacodynamics of ... Efzimfotase alfa (ALXN1850) is a second-generation TNSALP ERT in clinical development for the treatment of HPP (Patent US 2021/0169994 A1). Structurally related ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06079359

NCT06079359 | Phase 3 Study of ALXN1850 in Treatment- ... The primary purpose of this study is to evaluate the efficacy of ALXN1850 versus placebo on radiographic outcomes in pediatric participants with HPP who have ...

4. io.nihr.ac.uk io.nihr.ac.uk/wp-content/uploads/2025/07/36874-Efzimfotase-Alfa-for-Hypophosphatasia-V1.0-JUL2025-NON-CONF.pdf

Health Technology Briefing July 2025 Efzimfotase alfa works by replacing the alkaline phosphatase that the body needs to free phosphate. This allows it to bind together with calcium to build ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06079281

Phase 3 Study of ALXN1850 Versus Placebo in Adolescent ... The primary objective of this study is to assess the efficacy of ALXN1850 versus placebo on functional outcomes in adolescent and adult participants with HPP ...

6. academic.oup.com academic.oup.com/jbmr/article/39/10/1412/7732140

Safety, pharmacokinetics, and pharmacodynamics of ... Efzimfotase alfa (ALXN1850) is a second-generation TNSALP enzyme replacement therapy in development for HPP. This first-in-human open-label, ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04980248

Study of ALXN1850 in Participants With Hypophosphatasia ... This is an open-label, dose-escalating study to assess safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and immunogenicity of ALXN1850

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11920343/

Medical Management of Hypophosphatasia: Review ... Five-year efficacy and safety of asfotase alfa therapy for adults and adolescents with hypophosphatasia. ... hypophosphatasia: 7 year outcomes ...