ALXN1850 for Hypophosphatasia

(HICKORY Trial)

Not currently recruiting at 91 trial locations

Overseen By Alexion Pharmaceuticals, Inc. (Sponsor)

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Alexion Pharmaceuticals, Inc.

Disqualifiers: Cardiovascular, Respiratory, Hepatic, Renal, others

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: 78

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ALXN1850 for individuals with hypophosphatasia (HPP), a condition affecting bone strength and development. The goal is to determine if ALXN1850 improves daily functioning in people with HPP compared to a placebo (a substance with no active drug). Participants will initially receive either ALXN1850 or a placebo, and later, all will receive ALXN1850. This trial suits those diagnosed with HPP who have specific gene markers or lab results indicating lower than normal enzyme levels related to the condition. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have certain health conditions that affect drug absorption, metabolism, or elimination, you may be excluded from the trial.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that ALXN1850 is likely to be safe for humans?

Research shows that ALXN1850, also known as efzimfotase alfa, is generally safe for people. Previous studies found that adults with hypophosphatasia (HPP) usually tolerate this treatment well. Some patients experienced side effects, but these were mostly mild.

Earlier research also found that ALXN1850 helped reduce certain substances in the body linked to HPP. This suggests the treatment might not only be safe but also effective. Although the treatment remains under study, the safety results so far are encouraging for those considering joining the trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hypophosphatasia?

Most treatments for hypophosphatasia, like asfotase alfa, focus on replacing the enzyme alkaline phosphatase that's deficient in patients. But ALXN1850 works differently, offering a new formulation of the enzyme replacement therapy that might improve how the body uses it. Researchers are excited about ALXN1850 because it’s delivered as a subcutaneous injection every two weeks, which could be more convenient and potentially enhance patient adherence compared to existing treatments. Additionally, ALXN1850’s dosage is tailored to body weight, potentially allowing for more personalized treatment. This could mean better outcomes for patients with hypophosphatasia.

What evidence suggests that ALXN1850 might be an effective treatment for hypophosphatasia?

Research shows that ALXN1850, also known as efzimfotase alfa, can help people with hypophosphatasia (HPP). This trial will include an ALXN1850 group, where participants receive bodyweight-dependent doses of the treatment. ALXN1850 works by replacing an enzyme that helps the body use phosphate and calcium to build strong bones. Earlier studies found that it lowers certain disease indicators in the body. Previous trials demonstrated that the treatment is generally safe and may improve bone health in people with HPP. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adolescents and adults with Hypophosphatasia (HPP) who have a documented ALPL gene variant, low serum alkaline phosphatase activity without other causes than HPP, high plasma PLP levels, and reduced walking capacity. They must not have been treated with asfotase alfa before. People with hypoparathyroidism unrelated to HPP, recent fractures or surgeries that could affect the study, allergies to ingredients in the treatment or placebo, or significant health issues affecting drug absorption or posing risks are excluded.

Inclusion Criteria

Must meet 1 of the following criteria:

My medical records show a diagnosis of HPP.

My test shows an ALPL gene variant from a certified lab.

Exclusion Criteria

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

I have hypoparathyroidism not caused by HPP.

History of allergy or hypersensitivity to any ingredient contained in ALXN1850 or the placebo comparator (Table 9)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomized Evaluation Period

Participants receive either ALXN1850 or placebo via subcutaneous injection every 2 weeks for 24 weeks

24 weeks

12 visits (in-person)

Open-label Extension (OLE) Period

Participants receive ALXN1850 via subcutaneous injection every 2 weeks for up to 132 weeks

132 weeks

66 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ALXN1850
• Placebo

Trial Overview The trial is testing the effectiveness of a new medication called ALXN1850 compared to a placebo on improving physical function in participants with HPP. It's designed to see if those taking ALXN1850 perform better on functional tests like walking distance than those taking an inactive substance.

How Is the Trial Designed?

Group I: ALXN1850 Group Experimental Treatment 2 Interventions

Starting at Day 1 of the Randomized Evaluation Period, the ALXN1850 group will receive bodyweight dependent doses of either 20mg, 35mg or 50mg of ALXN1850 once q2w via SC injection, for 24 weeks. Participants will enter the OLE Period and continue q2w dosing with ALXN1850 for up to 132 weeks.

Group II: Placebo Group Placebo Group 1 Intervention

During the Randomized Evaluation Period, the placebo group will receive placebo on Day 1, followed by once every 2 weeks (q2w) via SC injection for 24 weeks. Participants will enter the OLE Period and receive bodyweight dependent doses of either 20mg, 35mg, or 50mg of ALXN1850 and continue q2w dosing with ALXN1850 for up to 132 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

In a 13-week study involving 27 adults with pediatric-onset hypophosphatasia, asfotase alfa, an enzyme replacement therapy, demonstrated increased exposure and consistent bioavailability across different body mass index categories, supporting its use at a recommended dose of 6 mg/kg/week.

The pharmacokinetics of asfotase alfa showed that its activity was dose-proportional and that steady state was achieved by approximately day 29, indicating effective dosing and potential for reliable treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia. Pan, WJ., Pradhan, R., Pelto, R., et al.[2022]

Asfotase alfa, the only approved treatment for hypophosphatasia (HPP), can interfere with thyroid hormone measurements in certain immunoassays that use alkaline phosphatase (ALP) as a labeling enzyme, leading to falsely low levels of free triiodothyronine (FT3) and free thyroxine (FT4).

In a study of three HPP patients, normal thyroid function was confirmed despite low FT3 and FT4 readings from the AIA-2000 immunoassay, highlighting the importance for clinicians to choose appropriate testing methods to avoid misinterpretation of thyroid function in patients receiving asfotase alfa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Altered Thyroid Function Tests Observed in Hypophosphatasia Patients Treated with Asfotase Alfa. Kato, H., Hidaka, N., Koga, 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]

Enzyme replacement therapy (ERT) with asfotase alfa has been shown to reduce the severity of oral manifestations in children with hypophosphatasia (HPP), based on a review of 22 studies.

Earlier initiation of ERT is recommended for better oral health outcomes, although some studies reported cases of further primary tooth loss, highlighting the need for more detailed research on oral health improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of enzyme replacement therapy on the oral health manifestations of hypophosphatasia among children: a scoping review. Smart, G., Jensen, ED., Poirier, BF., et al.[2023]

Asfotase alfa (AA), a bone-targeted enzyme replacement therapy, has significantly improved survival rates in severely affected infants with hypophosphatasia (HPP) and enhanced the quality of life for children and adults with the condition.

The review highlights the development of AA, including its design and clinical trial outcomes, while also addressing its limitations and potential adverse effects, establishing its critical role in the management of HPP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of asfotase alfa in the treatment of hypophosphatasia: design, development, and place in therapy. Bowden, SA., Foster, BL.[2023]

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]

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 ...