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

NCT ID: NCT03512314

Last Updated: 2025-03-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

11 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-01-24

Study Completion Date

2024-05-08

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

Conditions

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XIAP Deficiency NLRC4-MAS

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Tadekinig alfa

Active drug treatment during 26 weeks

Group Type EXPERIMENTAL

Tadekinig alfa

Intervention Type DRUG

Open label, 26 weeks on Tadekinig alfa treatment.

Interventions

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Tadekinig alfa

Open label, 26 weeks on Tadekinig alfa treatment.

Intervention Type DRUG

Other Intervention Names

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r-hIL-18BP

Eligibility Criteria

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Inclusion Criteria

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)
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AB2 Bio Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eduard Behrens, MD

Role: PRINCIPAL_INVESTIGATOR

Children Hospital of Philadelphia

Locations

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UCSD _ Department of Pediatrics / Rady Children's Hospital

La Jolla, California, United States

Site Status

Shands Children's Hospital

Gainsville, Florida, United States

Site Status

Children's Healthcare of Atlanta at Egleston

Atlanta, Georgia, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Children Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Texas Children's Hospital _ Baylor College of Medicine

Houston, Texas, United States

Site Status

The Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

CHU Sainte-Justine

Montreal, , Canada

Site Status

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

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Site Status

Countries

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United States Canada Germany

Other Identifiers

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OLE-NLRC4/XIAP.2016.001

Identifier Type: -

Identifier Source: org_study_id

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