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

NLRC4-MAS Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03512314
• Other study ID #: OLE-NLRC4/XIAP.2016.001
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 24, 2018
• Est. completion date: May 30, 2024

Study information

• Verified date: November 2023
• Source: AB2 Bio Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 10
• Est. completion date: May 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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)

Related Conditions & MeSH terms

• Genetic Diseases, X-Linked
• Lymphoproliferative Disorders
• NLRC4-MAS
• XIAP Deficiency

Intervention

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

Locations

Country	Name	City	State
Canada	CHU Sainte-Justine	Montréal
Canada	The Hospital for Sick Children	Toronto	Ontario
Germany	Universitätsklinikum Freiburg, Centrum für Chronische Immundefizienz (CCI) - Paediatric Unit	Freiburg	Baden-Württemberg
United States	Children's Healthcare of Atlanta at Egleston	Atlanta	Georgia
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Shands Children's Hospital	Gainesville	Florida
United States	Texas Children's Hospital _ Baylor College of Medicine	Houston	Texas
United States	UCSD _ Department of Pediatrics / Rady Children's Hospital	La Jolla	California
United States	Children Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
AB2 Bio Ltd.

Countries where clinical trial is conducted

United States,  Canada,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reports of adverse events	The incidence, nature and severity of AEs will be reported	26 weeks
Primary	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
Primary	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
Primary	Immunogenicity evaluation	Generation of anti-recombinant human Interleukin-18 Binding Protein (anti-rhIL-18BP) antibodies	26 weeks
Primary	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