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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: June 30, 2021

Detailed Description

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

Interventions

  • Drug: Tadekinig alfa
    • Open label, 26 weeks on Tadekinig alfa treatment.

Arms, Groups and Cohorts

  • Experimental: Tadekinig alfa
    • Active drug treatment during 26 weeks

Clinical Trial Outcome Measures

Primary Measures

  • Reports of adverse events
    • Time Frame: 26 weeks
    • The incidence, nature and severity of AEs will be reported
  • Reports of abnormal physical examination
    • Time Frame: 26 weeks
    • Measurements will be done using the modified Auto-inflammatory Disease Activity Index (mAIDAI) including multiple measurements aggregated as 1 / 0.
  • Reports of abnormal laboratory results
    • Time Frame: 26 weeks
    • Report of clinically significant abnormal laboratory results (i.eSerum CRP (ug/mL), Serum Ferritin (ng/mL). and any other abnormal lab results
  • Immunogenicity evaluation
    • Time Frame: 26 weeks
    • Generation of anti-recombinant human Interleukin-18 Binding Protein (anti-rhIL-18BP) antibodies
  • Evaluation of the local tolerability at the injection site
    • Time Frame: 26 weeks
    • 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.

Participating in This Clinical Trial

Inclusion Criteria

(both criteria must be met) 1. 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 2. Women of childbearing potential with negative urine pregnancy test (UPT) at all visits Exclusion Criteria:

1. 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 2. Evidence or history of malignancy 3. Evidence of invasive or life-threatening infection 4. History of tuberculosis 5. Life-threatening bleeding within 2 weeks of screening 6. Vaccination with a live vaccine within the previous 3 months 7. Evidence of severe organ compromise including but not limited to: (see details in the protocol) 8. Pregnant or breastfeeding females 9. Inability to follow highly effective birth control recommendations during the study and until 1 month after the end of the treatment. 10. Inability to provide informed consent, and also assent if applicable 11. Life expectancy less than 4 weeks 12. Concomitant use of other immunosuppression except NSAIDs, glucocorticoids, cyclosporine, tacrolimus, IL-1 inhibitors (Anakinra, Canakinumab, or Rilonacept)

Gender Eligibility: All

Minimum Age: N/A

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • AB2 Bio Ltd.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Eduard Behrens, MD, Principal Investigator, Children Hospital of Philadelphia
  • Overall Contact(s)
    • Eduardo Schiffrin, MD, +41 21 694 00 43, eduardo.schiffrin@ab2bio.com

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