Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency

Completed · Phase 3 · Has a placebo group

Conditions studied: NLRC4-MAS, XIAP Deficiency

In brief

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.

Key facts

Study ID: NCT03113760
Run by: AB2 Bio Ltd.
People needed: 15
Starts: 2017-07-21
Expected to finish: 2023-11-02
Last updated by the study team: 2025-07-02

Who can join

Age: any. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Patients with genetic diagnosis of NLRC4-MAS mutation or XIAP deficiency (caused by BIRC4 gene mutation) as confirmed by analysis performed at the central genetics laboratory. If possible, flow cytometry assay will be performed in parallel to confirm diagnosis of XIAP deficiency. (Note: Previous flow cytometry assay results will be permitted for confirmation of XIAP deficiency diagnosis.)
Patients with XIAP deficiency and a previous bone marrow transplantation are allowed, if they show evidence of primary or secondary graft failure, or failure to achieve phenotypic correction with evidence of XIAP-related disease recurrence or clinically significant mixed chimerism.
Ferritin ≥ 500 ng/mL or persistent elevation of CRP ≥ 2x ULN and mAIDAI ≥4
Patients receiving corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) or disease modifying anti-rheumatic drugs (DMARDs), and/or IL-1 blockade with insufficient response to treatment upon enrollment are allowed into the study. Patients not receiving any of these treatments before start of therapy are also allowed.
Women of childbearing potential with negative urine pregnancy test (UPT) at all visits (if UPT is positive, a blood test for human chorionic gonadotropin (hCG) to be performed) and who agree to follow highly effective birth control recommendations during the study and until 1 month after the end of the treatment. Birth control methods considered highly effective are: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner or sexual abstinence. In each case of delayed menstrual period (over one month between menstruations, confirmation of absence of pregnancy is strongly recommended. This recommendation also applies to women of childbearing potential with infrequent or irregular menstrual cycles. A post-study contraception duration of 4 weeks is recommended taking into account the median half-life of Tadekinig alfa of almost 40h and 5 half-lives representing a duration of 200 hours.

You may not qualify if…

Patients with life-threatening co-morbidities not associated with the underlying NLRC4-mutation or XIAP deficiency
Positive test for or prior history of HIV, Hepatitis B or Hepatitis C (serology)
Presence of active infections or a history of pulmonary TB infection with or without documented adequate therapy
Presence of life threatening infections
Oncologic causes of symptoms; current or previous history of malignancy
Presence of CNS manifestations (i.e. seizures, altered mental status, signs of increased intracranial pressure, chronic papilledema, loss of vision, other sensorineural deficiencies, etc.)
Patients suffering from biallelic mutations in any of the following genes: PRF1/Perforin, UNC13D/Munc 13-4, STX11/Syntaxin11, STXB2/Munc 18-2, RAB27A/Rab27a (Griscelli syndrome type 2), LYST (Chediak-Higashi syndrome), AP3B1, ADTB3A, HPS2 mutations (Hermansky-Pudlak syndrome 2) and X-linked lymphoproliferative syndrome (XLP)-1 with SH2D1A mutation
Patients who are pregnant or nursing, women of childbearing potential who are unwilling to use highly effective birth control methods (see definition in Inclusion Criteria above) through 4 weeks after the end of their participation in the study
Concomitant use of immunosuppression therapies excluded by the protocol. Note: NSAIDs, glucocorticoids, cyclosporine, tacrolimus, and IL-1 inhibitors (anakinra, canakinumab, or rilonacept, or others) are allowed
Patients and/or parents (or legal representative, if applicable) not willing to sign assent/informed consent
Hypersensitivity to the active substance or one of the excipients of the investigational product

Where it is running

UCSD _ Department of Pediatrics / Rady Children's Hospital — La Jolla, California, United States
Children's Healthcare of Atlanta at Egleston — Atlanta, Georgia, United States
Boston Children's Hospital — Boston, Massachusetts, United States
Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States
Children Hospital of Philadelphia — Philadelphia, Pennsylvania, United States
Texas Children's Hospital _ Baylor College of Medicine — Houston, Texas, United States
The Hospital for Sick Children — Toronto, Ontario, Canada
CHU Sainte-Justine — Montreal, Providence, Canada
Universitätsklinikum Freiburg, Centrum für Chronische Immundefizienz (CCI) - Paediatric Unit — Freiburg im Breisgau, Baden-Wurttemberg, Germany

Full record on ClinicalTrials.gov

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