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 ]

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