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

NCT03512314 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: OLE-NLRC4/XIAP.2016.001
• Study Type: interventional
• Target: 11
• Locations: 3 countries
• Sites: 11

Brief Summary

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.

Conditions

XIAP Deficiency; NLRC4-MAS

Outcome Measures

Primary Outcomes (5)

• 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

Study Arms (1)

Tadekinig alfa

EXPERIMENTAL

Active drug treatment during 26 weeks

Drug: Tadekinig alfa

Interventions

Tadekinig alfa DRUG

Open label, 26 weeks on Tadekinig alfa treatment.

Also known as: r-hIL-18BP

Tadekinig alfa

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• AB2 Bio Ltd.: lead

Study Sites (11)

UCSD _ Department of Pediatrics / Rady Children's Hospital

La Jolla, California, 92056, United States

Location

Shands Children's Hospital

Gainsville, Florida, 32610, United States

Location

Children's Healthcare of Atlanta at Egleston

Atlanta, Georgia, 30322, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Texas Children's Hospital _ Baylor College of Medicine

Houston, Texas, 77030, United States

Location

The Hospital for Sick Children

Toronto, Ontario, ON M5G 1X8, Canada

Location

CHU Sainte-Justine

Montreal, Canada

Location

Universitätsklinikum Freiburg, Centrum für Chronische Immundefizienz (CCI) - Paediatric Unit

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

MeSH Terms

Conditions

Lymphoproliferative Syndrome, X-Linked, 2

Study Officials

• Eduard Behrens, MD

  Children Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2018
• First Posted: April 30, 2018
• Study Start: January 24, 2018
• Primary Completion: April 8, 2024
• Study Completion: May 8, 2024
• Last Updated: March 17, 2025

Record last verified: 2025-01

Locations

CA (2); DE (1); US (8)