Therapeutic use of Tadekinig alfa in NLRC4 mutation and XIAP deficiency

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

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2018-003297-27-DE

Enrollment

Registered

2019-03-28

Start date

2019-10-15

Completion date

Unknown

Last updated

2023-11-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

NLRC4 mutation XIAP deficiency

Interventions

Product Name: Tadekinig alfa Product Code: r-hIL-18BP Pharmaceutical Form: Solution for injection INN or Proposed INN: Tadekinig alfa CAS Number: 220712-29-8 Current Sponsor code: r-hIL-18BPa Other d

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - Patients with genetic diagnosis of NLRC4-MAS mutation or XIAP deficiency (caused by BIRC4 gene mutation). 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.) A genetic diagnosis from a local laboratory will be accepted for enrolment and start of treatment, to avoid any treatment delays for these severe conditions. However, the genetic diagnosis has to be confirmed by the central laboratory. If the genetic diagnosis is not confirmed, the patient will discontinue the study. - 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. For these patients, genetic diagnosis at the central laboratory may show chimerism; thus, local genetic diagnosis prior to the bone marrow transplantation will be the main source to confirm the genetic diagnosis. - 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 Are the trial subjects under 18? yes Number of subjects for this age range: 13 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 2 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0

Exclusion criteria

Exclusion criteria: - 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 - Patients suffering from familial hemophagocytic lymphohistiocytosis (f HLH) - Patients who are pregnant or nursing, women of childbearing potential who are unwilling to use highly effective birth control methods - Concomitant use of immunosuppression therapies excluded by the protocol. - 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

Design outcomes

Primary

Measure	Time frame
Main Objective: - To assess clinical efficacy of Tadekinig alfa in monogenic autoinflammatory diseases with ongoing inflammation and deleterious mutations of NLRC4-MAS or XIAP - To assess laboratory/biological evidence of efficacy ;Secondary Objective: Secondary Efficacy Objective: - Main clinical features and laboratory biomarkers (characteristics of each patient profile) will be assessed longitudinally during the SAOL phase for each experimental subject Secondary Safety Objective: - To assess the safety and tolerability of Tadekinig alfa treatment in monogenic, autoinflammatory disease harboring deleterious mutations of NLRC4-MAS or XIAP ;Primary end point(s): The primary outcome is the time to first occurrence of disease reactivation (including full and partial disease reactivation) during the 16-week RW phase.;Timepoint(s) of evaluation of this end point: 16 weeks or occurence of first disease reactivation	—

Measure

Time frame

Main Objective: - To assess clinical efficacy of Tadekinig alfa in monogenic autoinflammatory diseases with ongoing inflammation and deleterious mutations of NLRC4-MAS or XIAP - To assess laboratory/biological evidence of efficacy ;Secondary Objective: Secondary Efficacy Objective: - Main clinical features and laboratory biomarkers (characteristics of each patient profile) will be assessed longitudinally during the SAOL phase for each experimental subject Secondary Safety Objective: - To assess the safety and tolerability of Tadekinig alfa treatment in monogenic, autoinflammatory disease harboring deleterious mutations of NLRC4-MAS or XIAP ;Primary end point(s): The primary outcome is the time to first occurrence of disease reactivation (including full and partial disease reactivation) during the 16-week RW phase.;Timepoint(s) of evaluation of this end point: 16 weeks or occurence of first disease reactivation

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Secondary

Measure	Time frame
Secondary end point(s): Key Secondary Efficacy Endpoint Response to therapy (including complete response and partial response) in the SAOL phase from Week 10 onwards and observed at least at 2 consecutive visits at least 2 weeks apart during the SAOL phase Other Secondary Efficacy Endpoints - Best response to therapy during the SAOL phase (including complete response and partial response and disease improvement) - Duration of response to therapy (including complete response and partial response) during the SAOL phase - Disease reactivation rate for individual subjects (number of disease reactivations experienced per week while each subject is on the study treatment during the SAOL phase) - Treatment failures (i.e. patients who experience at least one disease reactivation) - Intensity of disease reactivations (defined by the level of activity given by the mAIDAI – both objective and subjective criteria) - Serum CRP, Serum Ferritin - Improvement of fevers, improvement of hepato/splenomegaly (clinical assessments if present at Baseline) - Improvement in serum albumin and liver transaminases, anemia and/or platelet count (if present at Baseline) - Hospital length of stay - Length of hospitalisation - Physician Global Assessment - Patient’s or caregiver’s qualitative evaluation of health status - Presence of skin rash - evolution if present at Baseline or appearance during the study - Tolerance to oral/enteral nutrition for hospitalized patients if intestinal dysfunction was present at Baseline - Improvement of stool output for hospitalized patients if intestinal dysfunction was present at Baseline Safety and Tolerability Endpoints - Adverse events will be reported - Physical examination findings and vital signs: clinically significant changes from Baseline - Laboratory assessments including clinically significant changes from Baseline in hematology with platelet counts, CRP, ESR, ferritin, fibrinogen, D-dimer, liver enzymes, creatinine and glomerular filtr	—

Measure

Time frame

Secondary end point(s): Key Secondary Efficacy Endpoint Response to therapy (including complete response and partial response) in the SAOL phase from Week 10 onwards and observed at least at 2 consecutive visits at least 2 weeks apart during the SAOL phase Other Secondary Efficacy Endpoints - Best response to therapy during the SAOL phase (including complete response and partial response and disease improvement) - Duration of response to therapy (including complete response and partial response) during the SAOL phase - Disease reactivation rate for individual subjects (number of disease reactivations experienced per week while each subject is on the study treatment during the SAOL phase) - Treatment failures (i.e. patients who experience at least one disease reactivation) - Intensity of disease reactivations (defined by the level of activity given by the mAIDAI – both objective and subjective criteria) - Serum CRP, Serum Ferritin - Improvement of fevers, improvement of hepato/splenomegaly (clinical assessments if present at Baseline) - Improvement in serum albumin and liver transaminases, anemia and/or platelet count (if present at Baseline) - Hospital length of stay - Length of hospitalisation - Physician Global Assessment - Patient’s or caregiver’s qualitative evaluation of health status - Presence of skin rash - evolution if present at Baseline or appearance during the study - Tolerance to oral/enteral nutrition for hospitalized patients if intestinal dysfunction was present at Baseline - Improvement of stool output for hospitalized patients if intestinal dysfunction was present at Baseline Safety and Tolerability Endpoints - Adverse events will be reported - Physical examination findings and vital signs: clinically significant changes from Baseline - Laboratory assessments including clinically significant changes from Baseline in hematology with platelet counts, CRP, ESR, ferritin, fibrinogen, D-dimer, liver enzymes, creatinine and glomerular filtr

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Countries

Canada, Germany, United States

Contacts

Public ContactEduardo Schiffrin

AB2 Bio Ltd.

Eduardo.Schiffrin@ab2bio.com0041216940043

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026