Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency as Open Label Extension

Study Overview
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Brief Summary
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This is an open-label extension study for patients previously enrolled in the AB2 Bio Ltd. ongoing Phase III clinical trial NLRC4/XIAP.2016.001 (IND N° 127953). This OLE study will evaluate the long-term safety and tolerability of Tadekinig alfa in patients suffering from pediatric monogenic autoinflammatory diseases harboring deleterious mutations of NLRC4 and XIAP.

Detailed Description
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Pediatric auto-inflammatory conditions related to spontaneous activating mutations of the NLRC4 and with recurrent MAS-like flares with constitutive IL-18 hypersecretion, may require long-term blockade of the IL-18 pathway. Patients with X-linked inhibitor of apoptosis (XIAP) deficiency and suffering from Hemophagocytic-Lymphohistiocytosis (HLH), a MAS-like syndrome, also show high levels of serum IL-18 and may benefit from IL-18 blockade treatment until a curative hematopoietic stem cell transplantation can be performed The safety of IL-18 blockade during long-term periods is of major interest for the treatment of these patients

Official Title
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Open-label Extension Study With Tadekinig Alfa (r-hIL-18BP) to Monitor Safety and Tolerability in Patients With IL-18 Driven Monogenic Autoinflammatory Conditions: NLRC4 Mutation and XIAP Deficiency

Conditions
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XIAP Deficiency, NLRC4-MAS

Intervention / Treatment
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* Drug: Tadekinig alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (both criteria must be met) Patients have participated in AB2 Bio ltd. Phase III clinical trial NLRC4/XIAP.2016.001 (IND N° 127953) by one of the following mechanisms : a) Patients that have completed the first 18-week RCT phase of the preceding clinical trial but were not eligible for the RW phase due to flare symptoms. Or b) Patients that completed the first 18-week RCT phase and completed the RW phase of the preceding clinical trial. Or c) Patients who have exited either the RCT or RW phase of the preceding clinical trial due to treatment failure requiring rescue immunosuppression. Such patients must wait a minimum of 4 weeks after treatment discontinuation from the preceding clinical trial before enrolling in this OLE. If patients do not consent to enroll in the OLE after their early termination in the main study, they will be asked to continue with the planned visits of the main study Women of childbearing potential with negative urine pregnancy test (UPT) at all visits Exclusion Criteria: Patients may not enter the OLE if they voluntarily withdrew from RCT or RW study or if the time period between participation exceeds 3 months Evidence or history of malignancy Evidence of invasive or life-threatening infection History of tuberculosis Life-threatening bleeding within 2 weeks of screening Vaccination with a live vaccine within the previous 3 months Evidence of severe organ compromise including but not limited to: (see details in the protocol) Pregnant or breastfeeding females Inability to follow highly effective birth control recommendations during the study and until 1 month after the end of the treatment. Inability to provide informed consent, and also assent if applicable Life expectancy less than 4 weeks Concomitant use of other immunosuppression except NSAIDs, glucocorticoids, cyclosporine, tacrolimus, IL-1 inhibitors (Anakinra, Canakinumab, or Rilonacept)
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tadekinig alfa<br>Active drug treatment during 26 weeks | Drug: Tadekinig alfa<br>* Open label, 26 weeks on Tadekinig alfa treatment.<br>* Other names: r-hIL-18BP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reports of adverse events | The incidence, nature and severity of AEs will be reported | 26 weeks | 
| Reports of abnormal physical examination | Measurements will be done using the modified Auto-inflammatory Disease Activity Index (mAIDAI) including multiple measurements aggregated as 1 / 0. | 26 weeks | 
| Reports of abnormal laboratory results | Report of clinically significant abnormal laboratory results (i.eSerum CRP (ug/mL), Serum Ferritin (ng/mL). and any other abnormal lab results | 26 weeks | 
| Immunogenicity evaluation | Generation of anti-recombinant human Interleukin-18 Binding Protein (anti-rhIL-18BP) antibodies | 26 weeks | 
| Evaluation of the local tolerability at the injection site | Evaluation will be done based on the Local Tolerability Index where the patients will be asked to assess the degree of pain, redness, swelling, bruising, tenderness and itching, they are experiencing from each injection. | 26 weeks |