Clinical Trial: Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency
Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional
Official Title: Multicenter, Randomized, Double-blind, Placebo-controlled Trial With Tadekinig Alfa (r-hIL-18BP) in Patients With IL-18 Driven Monogenic Auto Inflammatory Conditions: NLRC4 Mutation and XIAP Deficienc
Brief Summary: This is a Phase 3 study to assess the safety and efficacy of Tadekinig alfa in patients with monogenic, interleukin-18 (IL 18) driven autoinflammation due to Nucleotide-binding oligomerization domain, leucine-rich repeat and caspase recruiting domain (CARD domain) containing 4 (NLRC4) - Macrophage activation syndrome (MAS) mutation (NLRC4-MAS mutation) or X-linked inhibitor of apoptosis (XIAP) deficiency. Because of the likelihood for pathogenic IL-18 in certain monogenic diseases, patients known to harbor deleterious mutations in NLRC4-MAS or XIAP and who have a history of ongoing inflammation will be enrolled if they have ferritin ≥ 500 ng/mL or persistent C reactive protein (CRP) elevation > 2 times the upper limit of normal (ULN) and the patients should have a Modified Autoinflammatory Disease Activity Index (mAIDAI) ≥ 4.
Detailed Summary:
Sponsor: AB2 Bio Ltd.
Current Primary Outcome: Incidence rate of flares [ Time Frame: 18 weeks ]
The primary outcome is the incidence rate of flares (number of flares over the 18-week study treatment period) corrected for duration of treatment.
Method of assessment : Biomarkers (CRP / Ferritin) and clinical manifestations of inflammation.
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Time to flare [ Time Frame: 22 weeks ]measured by the time spent from the resolution of the initial flare to the reactivation of the disease
- Intensity of flares [ Time Frame: 22 weeks ]Defined by the level of activity given by biomarkers and clinical manifestations
- Treatment failures [ Time Frame: 22 weeks ]Measured by the number of patients that do not respond to the combined treatment of standard of care with the study treatment
- Serum CRP, Serum Ferritin [ Time Frame: 22 weeks ]Laboratory measure ug/mL for CRP, and ng/mL for Ferritin
- Improvement of fevers, improvement of hepato/splenomegaly [ Time Frame: 22 weeks ]Clinical assessments if present at Baseline
- Improvement in serum albumin and liver transaminases, anemia and/or platelet count [ Time Frame: 22 weeks ]Laboratory measures if present at Baseline
- Hospital length of stay [ Time Frame: 22 weeks ]Length of hospitalisation
- Physician Global Assessment [ Time Frame: 22 weeks ]Measured through a scale 0 to 10
- Presence of skin rash - evolution if present at Baseline or appearance during the study [ Time Frame: 22 weeks ]Measured by the local tolerability index
- Tolerance to oral/enteral nutrition for hospitalized patients if intestinal dysfunction was present at Baseline [ Time Frame: 22 weeks ]Measured by the kcal per day
- Improvement of stool output for hospitalized patients if intestinal dysfunction was present at Baseline [ Time Frame: 22 weeks ]mL per 24hours
- Adverse events will be reported [ Time Frame: 22 weeks ]Including AESI (Adverse Events of Special Interest)
- Physical examination findings and vital signs [ Time Frame: 22 weeks ]Clinically significant changes from Baseline
- Laboratory assessments [ Time Frame: 22 weeks ]including clinically significant changes from Baseline in hematology with platelet counts, CRP, ESR, ferritin, fibrinogen, D-dimer, liver enzymes. (Followed until resolution)
- Immunogenicity evaluation [ Time Frame: 22 weeks ]Generation of anti-recombinant human IL-18BP (anti-rhIL-18BP) antibodies
- Local tolerability at the injection site [ Time Frame: 22 weeks ]Evaluated by a standardized assessment
Original Secondary Outcome: Same as current
Information By: AB2 Bio Ltd.
Dates:
Date Received: February 28, 2017
Date Started: May 2017
Date Completion: December 2018
Last Updated: April 10, 2017
Last Verified: April 2017