ALXN1850 for Hypophosphatasia
(CHESTNUT Trial)
Recruiting at 23 trial locations
AC
AP
AP
AP
Overseen ByAlexion Pharmaceuticals, Inc. (Sponsor)
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Waitlist Available
Sponsor: Alexion Pharmaceuticals, Inc.
Must be taking: Asfotase alfa
Disqualifiers: Cardiovascular, Respiratory, Hepatic, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
The primary purpose of this study is to assess the safety and tolerability of ALXN1850 versus asfotase alfa in pediatric participants with HPP previously treated with asfotase alfa.
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.
What data supports the effectiveness of the drug ALXN1850 for treating hypophosphatasia?
Eligibility Criteria
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.
See 1 more
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.
See 4 more
Treatment Details
Interventions
- ALXN1850 (Monoclonal Antibodies)
- asfotase alfa (Monoclonal Antibodies)
Trial OverviewThe 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.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: asfotase alfaExperimental Treatment1 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: ALXN1850Experimental Treatment2 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.
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
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
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]
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]
References
Interference of Asfotase Alfa in Immunoassays Employing Alkaline Phosphatase Technology. [2021]
Asfotase Alfa in Perinatal/Infantile-Onset and Juvenile-Onset Hypophosphatasia: A Guide to Its Use in the USA. [2022]
Asfotase Alfa: A Review in Paediatric-Onset Hypophosphatasia. [2022]
Impact of discontinuing 5 years of enzyme replacement treatment in a cohort of 6 adults with hypophosphatasia: A case series. [2022]
Five-year efficacy and safety of asfotase alfa therapy for adults and adolescents with hypophosphatasia. [2020]