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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03512314
Recruitment Status : Active, not recruiting
First Posted : April 30, 2018
Last Update Posted : November 8, 2023
Sponsor:
Information provided by (Responsible Party):
AB2 Bio Ltd.

Study Description
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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.

Condition or disease Intervention/treatment Phase
XIAP Deficiency NLRC4-MAS Drug: Tadekinig alfa Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 24, 2018
Estimated Primary Completion Date : April 30, 2024
Estimated Study Completion Date : May 30, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Tadekinig alfa
Active drug treatment during 26 weeks
 Drug: Tadekinig alfa
Open label, 26 weeks on Tadekinig alfa treatment.
Other Name: r-hIL-18BP


Outcome Measures
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Primary Outcome Measures :
  1. Reports of adverse events [ Time Frame: 26 weeks ]
    The incidence, nature and severity of AEs will be reported

  2. 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.

  3. 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

  4. Immunogenicity evaluation [ Time Frame: 26 weeks ]
    Generation of anti-recombinant human Interleukin-18 Binding Protein (anti-rhIL-18BP) antibodies

  5. 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.


Eligibility Criteria
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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03512314


Locations
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United States, California
UCSD _ Department of Pediatrics / Rady Children's Hospital
La Jolla, California, United States, 92056
United States, Florida
Shands Children's Hospital
Gainesville, Florida, United States, 32610
United States, Georgia
Children's Healthcare of Atlanta at Egleston
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
Texas Children's Hospital _ Baylor College of Medicine
Houston, Texas, United States, 77030
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, ON M5G 1X8
Canada
CHU Sainte-Justine
Montréal, Canada
Germany
Universitätsklinikum Freiburg, Centrum für Chronische Immundefizienz (CCI) - Paediatric Unit
Freiburg, Baden-Württemberg, Germany, 79106
Sponsors and Collaborators
AB2 Bio Ltd.
Investigators
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Principal Investigator: Eduard Behrens, MD Children Hospital of Philadelphia
More Information
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Responsible Party: AB2 Bio Ltd.
ClinicalTrials.gov Identifier: NCT03512314    
Other Study ID Numbers: OLE-NLRC4/XIAP.2016.001
First Posted: April 30, 2018    Key Record Dates
Last Update Posted: November 8, 2023
Last Verified: November 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: This information will be provided soon

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoproliferative Disorders
Genetic Diseases, X-Linked
Lymphatic Diseases
 Immunoproliferative Disorders
Immune System Diseases
Genetic Diseases, Inborn