Back to resultsTherapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency as Open Label Extension
Primary Purpose
XIAP Deficiency, NLRC4-MAS
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Tadekinig alfa
Sponsored by
About this trial
This is an interventional treatment trial for XIAP Deficiency
Eligibility Criteria
Inclusion Criteria: (both criteria must be met)
- 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
Exclusion Criteria:
- 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)
Sites / Locations
- UCSD _ Department of Pediatrics / Rady Children's HospitalRecruiting
- Shands Children's Hospital
- Children's Healthcare of Atlanta at EglestonRecruiting
- Boston Children's Hospital
- Cincinnati Children's Hospital Medical CenterRecruiting
- Children Hospital of PhiladelphiaRecruiting
- Children's Hospital of Pittsburgh of UPMC
- Texas Children's Hospital _ Baylor College of MedicineRecruiting
- The Hospital for Sick ChildrenRecruiting
- CHU Sainte-JustineRecruiting
- Universitätsklinikum Freiburg, Centrum für Chronische Immundefizienz (CCI) - Paediatric Unit
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tadekinig alfa
Arm Description
Active drug treatment during 26 weeks
Outcomes
Primary Outcome Measures
Reports of adverse events
The incidence, nature and severity of AEs will be reported
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.
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
Immunogenicity evaluation
Generation of anti-recombinant human Interleukin-18 Binding Protein (anti-rhIL-18BP) antibodies
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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03512314
Brief Title
Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency as Open Label Extension
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 24, 2018 (Actual)
Primary Completion Date
November 30, 2023 (Anticipated)
Study Completion Date
January 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AB2 Bio Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
XIAP Deficiency, NLRC4-MAS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Tadekinig alfa
Arm Type
Experimental
Arm Description
Active drug treatment during 26 weeks
Intervention Type
Drug
Intervention Name(s)
Tadekinig alfa
Other Intervention Name(s)
r-hIL-18BP
Intervention Description
Open label, 26 weeks on Tadekinig alfa treatment.
Primary Outcome Measure Information:
Title
Reports of adverse events
Description
The incidence, nature and severity of AEs will be reported
Time Frame
26 weeks
Title
Reports of abnormal physical examination
Description
Measurements will be done using the modified Auto-inflammatory Disease Activity Index (mAIDAI) including multiple measurements aggregated as 1 / 0.
Time Frame
26 weeks
Title
Reports of abnormal laboratory results
Description
Report of clinically significant abnormal laboratory results (i.eSerum CRP (ug/mL), Serum Ferritin (ng/mL). and any other abnormal lab results
Time Frame
26 weeks
Title
Immunogenicity evaluation
Description
Generation of anti-recombinant human Interleukin-18 Binding Protein (anti-rhIL-18BP) antibodies
Time Frame
26 weeks
Title
Evaluation of the local tolerability at the injection site
Description
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.
Time Frame
26 weeks
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: (both criteria must be met)
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
Exclusion Criteria:
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eduardo Schiffrin, MD
Phone
+41 21 694 00 43
Email
eduardo.schiffrin@ab2bio.com
First Name & Middle Initial & Last Name or Official Title & Degree
Friederike Stein, PhD
Phone
+41 21 694 00 40
Email
friederike.stein@ab2bio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eduard Behrens, MD
Organizational Affiliation
Children Hospital of Philadelphia
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCSD _ Department of Pediatrics / Rady Children's Hospital
City
La Jolla
State/Province
California
ZIP/Postal Code
92056
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Harold Hoffman, Dr.
Phone
858-966-1700
Ext
3422
Facility Name
Shands Children's Hospital
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Individual Site Status
Completed
Facility Name
Children's Healthcare of Atlanta at Egleston
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shanmuganathan Chandrakasan, MD
Phone
404-272-8877
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fatma Dedeoglu, Dr.
Phone
617-355-6117
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rebecca Marsh, Dr.
Phone
513-803-9063
Facility Name
Children Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ed Behrens, Dr.
Phone
267-426-0142
Email
behrens@email.chop.edu
Facility Name
Children's Hospital of Pittsburgh of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Individual Site Status
Completed
Facility Name
Texas Children's Hospital _ Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa Forbes, Dr.
Phone
832-824-1319
Facility Name
The Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
ON M5G 1X8
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ronald Laxer, M.D.
Phone
416-813-5068
Facility Name
CHU Sainte-Justine
City
Montréal
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julie Barsalou, MD
Phone
514-345-4931
Facility Name
Universitätsklinikum Freiburg, Centrum für Chronische Immundefizienz (CCI) - Paediatric Unit
City
Freiburg
State/Province
Baden-Württemberg
ZIP/Postal Code
79106
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stephan Ehl, MD
Phone
00497612707755
Email
Stephan.ehl@uniklinik-freiburg.de
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
This information will be provided soon
Learn more about this trial
Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency as Open Label Extension
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