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).
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Methotrexate will be administered SC or orally weekly for 104 weeks.
Rituximab will be administered intravenously (IV) continuously weekly, for up to 74 weeks.
Bortezomib will be administered via IV bolus or SC, as needed.
Number of Participants Who Achieve Immunosuppressive Therapy (IST) Complete Response at Week 100
Time frame: Week 100
Number Participants with Antidrug Antibodies (ADAs) and Neutralizing Antibodies (NAbs)
Time frame: Baseline Through Week 100
ADA and NAb Titer Levels
Time frame: Baseline Through Week 100
Serum Concentration of Asofatase Alfa (Measured as Enzyme Activity)
Time frame: Baseline Through Week 100
Plasma Concentration of Pyridoxal-5ˈ-Phosphate (PLP)
Time frame: Baseline Through Week 100
Plasma Concentration of Inorganic Pyrophosphates (PPi)
Time frame: Baseline Through Week 100
Number of Participants with Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events
Time frame: Baseline Through Week 104
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IVIg will be administered via IV monthly through initial 74 weeks.
Folic acid will be given orally as long as methotrexate is being dosed.