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

Hypophosphatasia Clinical Trial

— RESTORE  

Official title:

An Interventional, Prospective Open-Label Study of Immunosuppressive Therapies to Mitigate Immune-Mediated Loss of Therapeutic Response to Asfotase Alfa (STRENSIQ®) for Hypophosphatasia (RESTORE)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06015750
• Other study ID #: D8400C00001
• Secondary ID: AA-HPP-4072022-5
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: April 30, 2024
• Est. completion date: April 28, 2028

Study information

• Verified date: April 2024
• Source: Alexion Pharmaceuticals, Inc.
• Contact: Alexion Pharmaceuticals, Inc. (Sponsor)
• Phone: 1-855-752-2356
• Email: clinicaltrials[@]alexion.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 8
• Est. completion date: April 28, 2028
• Est. primary completion date: April 28, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 18 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Hypophosphatasia

Intervention

Drug:
• methotrexate
Methotrexate will be administered SC or orally weekly for 104 weeks.
• rituximab
Rituximab will be administered intravenously (IV) continuously weekly, for up to 74 weeks.
• bortezomib
Bortezomib will be administered via IV bolus or SC, as needed.
• IVIg
IVIg will be administered via IV monthly through initial 74 weeks.
• Folic Acid
Folic acid will be given orally as long as methotrexate is being dosed.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Achieve Immunosuppressive Therapy (IST) Complete Response at Week 100		Week 100
Secondary	Number Participants with Antidrug Antibodies (ADAs) and Neutralizing Antibodies (NAbs)		Baseline Through Week 100
Secondary	ADA and NAb Titer Levels		Baseline Through Week 100
Secondary	Serum Concentration of Asofatase Alfa (Measured as Enzyme Activity)		Baseline Through Week 100
Secondary	Plasma Concentration of Pyridoxal-5'-Phosphate (PLP)		Baseline Through Week 100
Secondary	Plasma Concentration of Inorganic Pyrophosphates (PPi)		Baseline Through Week 100
Secondary	Number of Participants with Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events		Baseline Through Week 104