Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency



Status:Recruiting
Conditions:Hematology
Therapuetic Areas:Hematology
Healthy:No
Age Range:Any - 17
Updated:3/7/2019
Start Date:July 21, 2017
End Date:July 2020
Contact:Eduardo Schiffrin, MD
Email:eduardo.schiffrin@ab2bio.com
Phone:+41 21 694 00 43

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Multicenter, Double-blind, Placebo-controlled, Randomized Withdrawal Trial With Tadekinig Alfa (r-hIL-18BP) in Patients With IL-18 Driven Monogenic Autoinflammatory Conditions: NLRC4 Mutation and XIAP Deficiency

This is a Phase 3 study to assess the safety and efficacy of Tadekinig alfa in patients with
monogenic, interleukin-18 (IL 18) driven autoinflammation due to Nucleotide-binding
oligomerization domain, leucine-rich repeat and caspase recruiting domain (CARD domain)
containing 4 (NLRC4) - Macrophage activation syndrome (MAS) mutation (NLRC4-MAS mutation) or
X-linked inhibitor of apoptosis (XIAP) deficiency. Because of the likelihood for pathogenic
IL-18 in certain monogenic diseases, patients known to harbor deleterious mutations in
NLRC4-MAS or XIAP and who have a history of ongoing inflammation will be enrolled if they
have ferritin ≥ 500 ng/mL or persistent C reactive protein (CRP) elevation ≥ 2 times the
upper limit of normal (ULN) and the patients should have a Modified Autoinflammatory Disease
Activity Index (mAIDAI) ≥ 4.

The study is designed with single-arm, open-label phase (SAOL) of Tadekinig alfa treatment
duration for 18-week followed by an 8-week Randomized Withdrawal (RW) period for efficacy and
safety evaluation, with no interruption between the two phases of treatment. The screening
period will occur before the SAOL phase and before the first dose of Investigational
Medicinal Product (IMP)

INCLUSION CRITERIA

1. Patients ≤ 17 years of age

2. Patients with genetic diagnosis of NLRC4-MAS mutation or XIAP deficiency (caused by
BIRC4 gene mutation)

3. Ferritin ≥ 500 ng/mL or persistent elevation of CRP ≥ 2x ULN and mAIDAI ≥4

4. Patients receiving stable doses of corticosteroids, non-steroidal anti-inflammatory
drugs (NSAIDs) or disease modifying anti rheumatic drugs (DMARDs), and/or IL-1
blockade for at least 2 weeks prior to enrollment are allowed into the study. Patients
not receiving any of these treatments before start of therapy are also allowed

5. Women of childbearing potential with negative urine pregnancy test (UPT) at all visits

EXCLUSION CRITERIA

1. Patients > 17 years of age

2. Positive test for or prior history of HIV, Hepatitis B or Hepatitis C (serology)

3. Presence of active infections or a history of pulmonary TB infection with or without
documented adequate therapy

4. Presence of life threatening infections

5. Oncologic causes of symptoms; current or previous history of malignancy

6. Presence of CNS manifestations

7. Patients suffering from familial hemophagocytic lymphohistiocytosis (f HLH)

8. Patients who are pregnant or nursing, women of childbearing potential who are
unwilling to use highly effective birth control methods

9. Concomitant use of immunosuppression therapies excluded by the protocol.

10. Patients and/or parents (or legal representative, if applicable) not willing to sign
assent/informed consent
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Atlanta, Georgia 30322
Phone: 404-727-8877
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3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
 1-513-636-4200 
Phone: 513-803-9063
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
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4401 Penn Avenue
Pittsburgh, Pennsylvania 15224
412-692-5325
Phone: 412-692-9934
Children's Hospital of Pittsburgh of UPMC UPMC is one of the leading nonprofit health systems...
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300 Longwood Ave
Boston, Massachusetts 02115
(617) 355-6000
Phone: 617-355-6117
Boston Children's Hospital Boston Children's Hospital is a 395-bed comprehensive center for pediatric health care....
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Houston, Texas 77030
Phone: 832-824-1319
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La Jolla, California 92056
Phone: 858-966-1700
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3401 Civic Center Boulevard
Philadelphia, Pennsylvania 19104
Phone: 267-425-2050
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555 University Avenue
Toronto, Ontario M5G 1X8
Phone: 416-813-5068
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