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

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

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.

Study Overview

• Status: Completed
• Conditions: NLRC4-MAS; XIAP Deficiency
• Intervention / Treatment: Drug: Tadekinig alfa

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

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Montréal, Canada
    • CHU Sainte-Justine
  • Ontario
    • Toronto, Ontario, Canada, ON M5G 1X8
      • The Hospital for Sick Children
• Germany
  • Baden-Württemberg
    • Freiburg, Baden-Württemberg, Germany, 79106
      • Universitätsklinikum Freiburg, Centrum für Chronische Immundefizienz (CCI) - Paediatric Unit
• United States
  • California
    • La Jolla, California, United States, 92056
      • UCSD _ Department of Pediatrics / Rady Children's Hospital
  • Florida
    • Gainsville, Florida, United States, 32610
      • Shands Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta at Egleston
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital _ Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AB2 Bio Ltd.
• Investigators: Principal Investigator: Eduard Behrens, MD, Children Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2018
• Primary Completion (Actual): April 8, 2024
• Study Completion (Actual): May 8, 2024

Study Registration Dates

• First Submitted: April 9, 2018
• First Submitted That Met QC Criteria: April 19, 2018
• First Posted (Actual): April 30, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 13, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Immune System Diseases; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoproliferative Disorders; Genetic Diseases, X-Linked
• Other Study ID Numbers: OLE-NLRC4/XIAP.2016.001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: This information will be provided soon

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No