Clinical trial NCT06015750: Mitigate Immune-Mediated Loss of Therapeutic Response to Asfotase Alfa (STRENSIQ®) for Hypophosphatasia
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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Hypophosphatasia
Keywords: Hypophosphatasia
HPP
Asfotase alfa
Strensiq
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2023-08-29
Enrollment: 8
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Detailed description: The administration of biological drugs to patients, especially for chronic conditions, carries a risk of eliciting anti-drug antibodies. Neutralizing antibodies can neutralize the clinical benefit of the agent. In postmarketing safety surveillance, some patients treated with asfotase alfa demonstrated an initial response, but subsequently recurrence and progression of disease. Consequently, the FDA requested a study to assess a potential serious risk of immune-mediated loss of effectiveness.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Who Achieve Immunosuppressive Therapy (IST) Complete Response at Week 100
timeFrame: Week 100
Secondary outcomes:
measure: Number Participants with Antidrug Antibodies (ADAs) and Neutralizing Antibodies (NAbs)
timeFrame: Baseline Through Week 100
measure: ADA and NAb Titer Levels
timeFrame: Baseline Through Week 100
measure: Serum Concentration of Asofatase Alfa (Measured as Enzyme Activity)
timeFrame: Baseline Through Week 100
measure: Plasma Concentration of Pyridoxal-5ˈ-Phosphate (PLP)
timeFrame: Baseline Through Week 100
measure: Plasma Concentration of Inorganic Pyrophosphates (PPi)
timeFrame: Baseline Through Week 100
measure: Number of Participants with Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events
timeFrame: Baseline Through Week 104
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Le Kremlin-Bicêtre
country: France
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
References: