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

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ClinicalTrials.gov Identifier: NCT03512314
Recruitment Status : Recruiting
First Posted : April 30, 2018
Last Update Posted : October 22, 2020
Sponsor:
Information provided by (Responsible Party):
AB2 Bio Ltd.

Tracking Information
First Submitted Date  ICMJE April 9, 2018
First Posted Date  ICMJE April 30, 2018
Last Update Posted Date October 22, 2020
Actual Study Start Date  ICMJE January 24, 2018
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 19, 2018)
  • Reports of adverse events [ Time Frame: 26 weeks ]
    The incidence, nature and severity of AEs will be reported
  • 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.
  • 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
  • Immunogenicity evaluation [ Time Frame: 26 weeks ]
    Generation of anti-recombinant human Interleukin-18 Binding Protein (anti-rhIL-18BP) antibodies
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency as Open Label Extension
Official Title  ICMJE 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
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • XIAP Deficiency
  • NLRC4-MAS
Intervention  ICMJE Drug: Tadekinig alfa
Open label, 26 weeks on Tadekinig alfa treatment.
Other Name: r-hIL-18BP
Study Arms  ICMJE Experimental: Tadekinig alfa
Active drug treatment during 26 weeks
Intervention: Drug: Tadekinig alfa
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 19, 2018)		 10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 28, 2022
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Eduardo Schiffrin, MD +41 21 694 00 43 eduardo.schiffrin@ab2bio.com
Contact: Friederike Stein, PhD +41 21 694 00 40 friederike.stein@ab2bio.com
Listed Location Countries  ICMJE Canada,   Germany,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03512314
Other Study ID Numbers  ICMJE OLE-NLRC4/XIAP.2016.001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: This information will be provided soon
Responsible Party AB2 Bio Ltd.
Study Sponsor  ICMJE AB2 Bio Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Eduard Behrens, MD Children Hospital of Philadelphia
PRS Account AB2 Bio Ltd.
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP