Ongoing Clinical Trials for Hypophosphatasia
Hypophosphatasia is a rare genetic disorder affecting bone and teeth development. Currently, 4 clinical trials are ongoing across Europe, testing new treatment approaches including ALXN1850, a novel enzyme replacement therapy, and immunosuppressive strategies for patients who have developed resistance to existing treatments. These studies are recruiting children, adolescents, and adults at various stages of the disease.
Clinical trial locations
- Austria
- Belgium
- Finland
- France
- Study of ALXN1850 for Children Aged 2 to 12 with Hypophosphatasia Who Have Not Previously Received Asfotase Alfa Treatment
- Study on ALXN1850 and Asfotase Alfa for Children Aged 2-12 with Hypophosphatasia Previously Treated with Asfotase Alfa
- Study on ALXN1850 for Adolescents and Adults with Hypophosphatasia Not Previously Treated with Asfotase Alfa
- Study on Immunosuppressive Therapies with Asfotase Alfa for Patients with Hypophosphatasia Experiencing Reduced Treatment Effectiveness
- Germany
- Italy
- Study of ALXN1850 for Children Aged 2 to 12 with Hypophosphatasia Who Have Not Previously Received Asfotase Alfa Treatment
- Study on ALXN1850 and Asfotase Alfa for Children Aged 2-12 with Hypophosphatasia Previously Treated with Asfotase Alfa
- Study on ALXN1850 for Adolescents and Adults with Hypophosphatasia Not Previously Treated with Asfotase Alfa
- Poland
- Romania
- Slovakia
- Spain
- Sweden
Study of ALXN1850 for Children Aged 2 to 12 with Hypophosphatasia Who Have Not Previously Received Asfotase Alfa Treatment
This trial is evaluating ALXN1850, a new enzyme replacement therapy, in children aged 2 to under 12 years who have never received asfotase alfa treatment before. The study is being conducted across multiple European countries including Belgium, Romania, Sweden, Finland, Poland, France, Italy, and Spain.
Who can join: Children must have a documented diagnosis of hypophosphatasia with signs of rickets visible on X-rays. They must have low levels of alkaline phosphatase in their blood and show genetic evidence of the condition either through a confirmed ALPL gene mutation or elevated levels of pyridoxal 5′-phosphate. Participants must be at Tanner stage 2 or less, meaning they are in early stages of physical development. Parents or guardians must provide written consent.
Who cannot join: Children who have previously been treated with asfotase alfa are excluded. Additionally, those with other medical conditions that might interfere with the study, those unable to follow study procedures, or those participating in another clinical trial at the same time cannot take part.
What the study involves: This is a placebo-controlled trial where participants will be randomly assigned to receive either ALXN1850 or a placebo through injections under the skin. The main goal is to assess how well ALXN1850 improves bone health, particularly looking at changes in rickets severity on X-rays. The study will also measure physical performance, quality of life, and safety throughout the evaluation period lasting until Day 169, with the overall study expected to conclude by December 2027.
Investigational drug: ALXN1850 is a solution for subcutaneous injection designed to replace the deficient alkaline phosphatase enzyme in children with hypophosphatasia, potentially improving bone mineralization and reducing skeletal abnormalities.
Study on ALXN1850 and Asfotase Alfa for Children Aged 2-12 with Hypophosphatasia Previously Treated with Asfotase Alfa
This trial compares ALXN1850 with the established treatment asfotase alfa in children aged 2 to under 12 years who have already been receiving asfotase alfa for at least 6 months. The study is taking place in Italy, France, and Germany.
Who can join: Children must have a documented diagnosis of hypophosphatasia with open growth plates visible on X-rays. They must be at Tanner stage 2 or less and have been receiving asfotase alfa at a dose of 6 mg per kg per week for at least 6 months before joining the study. This treatment should have been given either as 2 mg per kg three times weekly or 1 mg per kg six times weekly. Parents or guardians must provide written consent, and children must give their assent where applicable.
Who cannot join: Children who have not previously received asfotase alfa treatment are excluded. Those with other medical conditions that might interfere with the study, inability to follow study procedures, participation in another trial, history of serious allergic reactions, or those who are pregnant or breastfeeding cannot participate.
What the study involves: Participants will be randomly assigned to receive either ALXN1850 or continue with asfotase alfa through subcutaneous injections. The primary focus is on assessing the safety and tolerability of ALXN1850 compared to asfotase alfa. Regular monitoring will occur throughout the study, with assessments of health measures, physical function, and quality of life up to Day 169. The trial is expected to conclude by December 2027.
Investigational drugs: ALXN1850 is the new medication being tested, while asfotase alfa serves as the comparison treatment. Both are enzyme replacement therapies administered through injections under the skin to help improve bone health in children with hypophosphatasia.
Study on ALXN1850 for Adolescents and Adults with Hypophosphatasia Not Previously Treated with Asfotase Alfa
This trial evaluates ALXN1850 in adolescents aged 12 and older and adults who have never received asfotase alfa treatment. The study is being conducted across Germany, Spain, France, Belgium, Poland, Italy, Slovakia, and Austria.
Who can join: Participants must be at least 12 years old with a documented diagnosis of hypophosphatasia. They need to have either a confirmed mutation in the ALPL gene or elevated levels of pyridoxal 5′-phosphate. Additionally, participants must show low serum alkaline phosphatase activity below the normal range for their age and sex. A key requirement is demonstrating reduced physical function through two separate 6-minute walk tests showing distance below 85% of what is expected for their age, sex, weight, and height. Importantly, participants must not be willing or able to receive asfotase alfa for any reason. Those who can have children must follow specific birth control requirements.
Who cannot join: Individuals who have previously been treated with asfotase alfa are excluded, as are those outside the specified age range or belonging to vulnerable populations requiring special protection.
What the study involves: This is a double-blind, placebo-controlled trial where participants are randomly assigned to receive either ALXN1850 or placebo through subcutaneous injections. The study focuses on measuring improvements in physical function, particularly through the 6-minute walk test, as well as other functional assessments like the 30-second sit-to-stand test and Timed Up-and-Go test. Regular blood tests and health monitoring will occur throughout the evaluation period ending on Day 169.
Investigational drug: ALXN1850 is a recombinant alkaline phosphatase enzyme replacement therapy designed to improve bone mineralization and physical function in adolescents and adults with hypophosphatasia.
Study on Immunosuppressive Therapies with Asfotase Alfa for Patients with Hypophosphatasia Experiencing Reduced Treatment Effectiveness
This unique trial addresses a specific challenge faced by some patients: the development of antibodies that reduce the effectiveness of asfotase alfa treatment. The study is taking place in France.
Who can join: Participants must be between 2 and 18 years old with open growth plates. They must have initially responded well to asfotase alfa after at least 6 months of continuous treatment but have experienced a return or worsening of rickets symptoms for at least the past 3 months while still receiving the medication. Crucially, participants must have developed anti-drug antibodies, with or without neutralizing antibodies, confirmed by a Treatment Monitoring Board. Both males and females can participate, with specific contraception requirements for those of childbearing potential. Parents or guardians must provide informed consent.
Who cannot join: Patients without hypophosphatasia, those not experiencing immune-mediated loss of treatment effectiveness, and those ineligible for immunosuppressive therapies are excluded from the study.
What the study involves: Participants will continue receiving asfotase alfa while also receiving immunosuppressive therapies to reduce the immune system’s attack on the medication. The immunosuppressive treatments may include rituximab, bortezomib, and methotrexate disodium, administered either intravenously or orally. Some participants may receive a placebo for comparison. The study will closely monitor antibody levels, enzyme activity, and rickets improvement through regular blood tests, physical examinations, and imaging. The primary goal is to achieve a complete response by Week 100, defined as decreased antibody levels and improvement in rickets severity. The trial is expected to conclude by August 2027.
Investigational approach: This trial combines asfotase alfa with immunosuppressive therapies. Asfotase alfa is the established enzyme replacement therapy for hypophosphatasia, while the immunosuppressive medications aim to prevent the immune system from developing antibodies that interfere with treatment effectiveness.
Summary
Four clinical trials are currently ongoing for hypophosphatasia across Europe, representing a comprehensive research effort to improve treatment options for patients of all ages. Three trials focus on ALXN1850, a novel enzyme replacement therapy, targeting different patient populations: treatment-naïve children aged 2-12, treatment-experienced children in the same age range, and adolescents and adults aged 12 and older. These trials are spread across multiple countries, with France, Italy, Belgium, Spain, and Germany hosting multiple studies.
A notable feature of the research landscape is the concentration of trials in France, which hosts all four studies, likely reflecting specialized centers of excellence in treating this rare condition. The fourth trial takes an innovative approach by addressing treatment resistance through immunosuppressive therapies, offering hope for patients who have developed antibodies against asfotase alfa.
ALXN1850 appears to be the primary focus of current research, with three trials evaluating its safety and effectiveness across different age groups and treatment histories. This coordinated research effort suggests a systematic approach to understanding how this new therapy might benefit patients at various stages of disease and treatment. All studies are expected to conclude by 2027, which will provide important data to guide future treatment decisions for hypophosphatasia.
