Mitigate Immune-Mediated Loss of Therapeutic Response to Asfotase Alfa (STRENSIQ®) for Hypophosphatasia

NCT06015750 | Withdrawn Phase 4 FDA Drug

• 3 other identifiers: D8400C00001AA-HPP-4072022-502793-17
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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).

Conditions

Hypophosphatasia

Keywords

Hypophosphatasia; HPP; Asfotase alfa; Strensiq

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Achieve Immunosuppressive Therapy (IST) Complete Response at Week 100

  Week 100

Secondary Outcomes (6)

• Number Participants with Antidrug Antibodies (ADAs) and Neutralizing Antibodies (NAbs)

  Baseline Through Week 100

• ADA and NAb Titer Levels

  Baseline Through Week 100

• Serum Concentration of Asofatase Alfa (Measured as Enzyme Activity)

  Baseline Through Week 100

• Plasma Concentration of Pyridoxal-5ˈ-Phosphate (PLP)

  Baseline Through Week 100

• Plasma Concentration of Inorganic Pyrophosphates (PPi)

  Baseline Through Week 100

Study Arms (1)

Pediatric participants with HPP

EXPERIMENTAL

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

Drug: methotrexate; Drug: rituximab; Drug: bortezomib; Drug: IVIg; Drug: Folic Acid

Interventions

methotrexate DRUG

Methotrexate will be administered SC or orally weekly for 104 weeks.

Pediatric participants with HPP

rituximab DRUG

Rituximab will be administered intravenously (IV) continuously weekly, for up to 74 weeks.

Pediatric participants with HPP

bortezomib DRUG

Bortezomib will be administered via IV bolus or SC, as needed.

Pediatric participants with HPP

IVIg DRUG

IVIg will be administered via IV monthly through initial 74 weeks.

Pediatric participants with HPP

Folic Acid DRUG

Folic acid will be given orally as long as methotrexate is being dosed.

Pediatric participants with HPP

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Reoccurrence or worsening of rickets for at least the past 3 months in participants who showed an initial efficacy response to asfotase alfa after at least 6 months of continuous treatment and currently receiving asfotase alfa. RSS will be used to determine severity at Baseline.
• Presence of ADAs, with or without NAbs, irrespective of their titers.
• Confirmation by the TMB that both the clinical evidence and immunogenicity-mediated association noted above are present.
• Female participants of childbearing potential and male participants with partners of childbearing potential must follow protocol-specified contraception guidance as described in Section 10.5.
• Participant, or participant's legal guardian, is capable of signing informed consent or assent as described in Section 10.1.3, which includes compliance with the requirements and restrictions listed in the informed consent or assent form and in this protocol.

You may not qualify if:

• Known history of human immunodeficiency virus (HIV) infection (evidenced by HIV type 1 or type 2 \[HIV 1, HIV 2\] antibody) or hepatitis B or C viral infection.
• Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to Screening.
• Inability of the participant, or the participant's legal guardian, to provide informed consent.
• Pregnant, breastfeeding, or intending to conceive during the course of the study.
• Inability to travel to the clinic for specified visits during the Treatment Period caused by disease per se or logistics (does not apply to external travel restrictions).
• The participant is at risk of reactivation or has an active significant viral infection such as hepatitis B, cytomegalovirus, herpes simplex, human polyomavirus (also known as John Cunningham \[JC\] virus), parvovirus, or Epstein Barr virus.
• The participant is at risk of reactivation of tuberculosis or has regular contact (eg, in the household) with individuals who are being actively treated for tuberculosis.
• The participant has had or is required to have any live vaccination within 1 month prior to enrollment.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

MeSH Terms

Conditions

Hypophosphatasia

Interventions

Methotrexate; Rituximab; Bortezomib; Immunoglobulins, Intravenous; Folic Acid

Condition Hierarchy (Ancestors)

Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Immunoglobulin G; Immunoglobulin Isotypes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2023
• First Posted: August 29, 2023
• Study Start (Estimated): July 29, 2026
• Primary Completion (Estimated): March 13, 2030
• Study Completion (Estimated): March 13, 2030
• Last Updated: December 18, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR