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NLRC4-MASPhase 3NCT03113760

Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency

A Phase 3 study testing Tadekinig alfa and 0.9% sodium chloride in people with NLRC4-MAS and XIAP Deficiency, run by AB2 Bio Ltd. at 9 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Any age
Conditions the study is for
NLRC4-MAS, XIAP Deficiency
What is being tested?
Tadekinig alfa and 0.9% sodium chloride
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
15 participants
Where
9 sitesin 3 countries
Study dates
21 Jul 2017to 2 Nov 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.)
Show all 11Show fewer
  • 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

Trial locations and contacts

9 sites in 3 countries.

9 sites in 3 countries

United States6 sites
  • Children's Healthcare of Atlanta at Egleston

    Atlanta, Georgia, 30322

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Texas Children's Hospital _ Baylor College of Medicine

    Houston, Texas, 77030

  • UCSD _ Department of Pediatrics / Rady Children's Hospital

    La Jolla, California, 92056

  • Children Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

Other trials in United States

Canada2 sites
  • CHU Sainte-Justine

    Montreal, Providence, QC H3T 1C5

  • The Hospital for Sick Children

    Toronto, Ontario, ON M5G 1X8

Other trials in Canada

Germany1 site
  • Universitätsklinikum Freiburg, Centrum für Chronische Immundefizienz (CCI) - Paediatric Unit

    Freiburg im Breisgau, Baden-Wurttemberg, 79106

Other trials in Germany

About this study

Official title: 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.

Read the detailed description

The study is designed with single-arm, open-label phase (SAOL) of Tadekinig alfa treatment duration for 18-week followed by an up to 16-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)

Being tested
Tadekinig alfa, 0.9% sodium chloride
Medical subject headings
Lymphoproliferative Syndrome, X-Linked, 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tadekinig alfaDrug

    Also called IL-18BP, r-hIL-18BP

    Tadekinig alfa is a soluble glycoprotein of 164 amino acids produced from Chinese Hamster Ovary cell line. Tadekinig alfa is supplied as a colorless to slightly yellow, sterile solution for injection in glass vials containing sodium chloride, and 0.02M sodium phosphate buffer as excipients. It is available in a concentration of 20mg/0.5mL.

  • 0.9% sodium chlorideOther

    To ensure that the treatment remains blinded for the entire study period, the placebo solutions will be supplied in identical vials and similar labelling as the active drug and will be indistinguishable in terms of their texture, color, and smell.

Study groups in NCT03113760
Study groupRoleWhat they receive
Tadekinig alfaExperimentalPatients that showed response to treatment in the SAOL phase will receive Tadekinig alfa for up to 16 weeks.
Receives: Drug: Tadekinig alfa
0.9% sodium chloridePlacebo comparatorPatients that showed response to treatment in the SAOL phase will receive placebo comparator for up to 16 weeks.
Receives: Other: 0.9% sodium chloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Prevention of Flares

    The primary outcome measure is the time to first occurrence of disease reactivation during the 16-week RW phase.

    Method of assessment: Biomarkers (CRP / Ferritin) and clinical manifestations of systemic inflammation and end-organ damage.

    Measured: 16 weeks

Secondary outcomes (21)
  1. Best Response

    Best response to therapy during the SAOL phase including either complete response, partial response or disease improvement.

    Method of assessment: Biomarkers (CRP / Ferritin) and clinical manifestations of systemic inflammation and end-organ damage.

    Measured: 18 weeks

  2. Duration of Response During the SAOL Phase (Until End of Phase or Disease Reactivation)

    Duration of response to therapy during the SAOL phase is assessed for patients having achieved a complete or partial response to therapy during the SAOL phase. It is defined as the time from first evaluation of partial or complete response until the time of subsequent disease reactivation or end of SAOL phase, whichever occurs first.

    Of the 11 patients achieving partial or complete response during the SAOL phase, 8 maintained treatment response until the end of the SAOL phase.

    2 of the 11 patients had a temporary disease reactivation during the protocol mandated steroid weaning in the SAOL phase; 1 of the 11 patients was withdrawn from blinded treatment following a disease reactivation.

    Measured: The actual mean treatment duration in the SAOL phase was 17.6 weeks (minimum / maximum 5.9 / 22.1 weeks).

  3. Change From Baseline in mAIDAI Total Score in the SAOL Phase

    The mAIDAI (modified autoinflammatory disease activitiy index) is an assessment of global disease activity that measures 14 different components for disease as either absent (0 points) or present (2 points for Uveitis 3+/4+ and 1 point for all other symptoms) at each visit. The mAIDAI total score is the sum of the points assigned across all components and ranges from 0 to 15, with a higher score indicating more severe disease activity.

    Measured: 18 weeks

  4. Change From Baseline in Serum Ferritin

    Laboratory measure

    Measured: 34 weeks

  5. Change From Baseline in Serum CRP

    Laboratory measure

    Measured: 34 weeks

  6. Resolution of Fevers, Hepato/Splenomegaly and Skin Rash

    Clinical assessments if present at Baseline; number displays percentage of patients with resolution of individual disease component at Week 18 or early termination visit based on the number of patients with a baseline assessment for the component of interest.

    Measured: 18 weeks

  7. Improvement in Laboratory Markers - AST (SGOT)

    Change from Baseline mean value to Week 18 mean value

    Measured: 18 weeks

  8. Improvement in Laboratory Markers - ALT (SGPT)

    Change from Baseline mean value to Week 18 mean value

    Measured: 18 weeks

  9. Improvement in Laboratory Markers - Albumin

    Change from Baseline mean value to Week 18 mean value

    Measured: 18 weeks

  10. Improvement in Laboratory Markers - Hemoglobin

    Change from Baseline mean value to Week 18 mean value

    Measured: 18 weeks

  11. Improvement in Laboratory Markers - Platelets

    Change from Baseline mean value to Week 18 mean value

    Measured: 18 weeks

  12. Improvement in Laboratory Markers - Erythrocyte Sedimentation Rate

    Change from Baseline mean value to Week 18 mean value

    Measured: 18 weeks

  13. Improvement in Laboratory Markers - Fibrinogen

    Change from Baseline mean value to Week 18 mean value

    Measured: 18 weeks

  14. Improvement in Laboratory Markers - D-Dimer

    Change from Baseline mean value to Week 18 mean value

    Measured: 18 weeks

  15. Hospital Length of Stay

    Length of hospitalisation; emergency room attendance and unscheduled visits for treatment of disease reactivations not included

    Measured: 34 weeks

  16. Change in Physician Global Assessment (PGA)

    The PGA is a direct surrogate of how a patient functions and assesses the severity of disease-related (auto-inflammatory) symptoms by selecting an integer score from 0 (no impact on subject; no symptoms) to 10 (no normal activities possible; highest severity of symptoms possible).

    The outcome lists the change from baseline of treatment phase to end of treatment phase/study in the PGA symptom severity score.

    Measured: 34 weeks

  17. Change in Patient/Caregiver Qualitative Evaluation of Health Status in Randomized Withdrawal Phase

    The individual disease-related symptoms score is the sum of (x) individual symptom scores within domain each ranging from 0 (None) to 5 (Very severe) for: general wellbeing (5), gastrointestinal (7), musculoskeletal (5), skin (2), eye (2), central nervous system (3), and lymphatic (2). Highest values indicate more severe disease-related symptoms within total score range from 0-130.

    Measured: 16 weeks

  18. Immunogenicity Evaluation

    Generation of anti-recombinant human IL-18BP (anti-rhIL-18BP) antibodies

    Measured: 34 weeks (SAOL + RW phases)

  19. Local Tolerability at the Injection Site (as Defined by Number of Participants With Adverse Events of Special Interest)

    Adverse events of special interest (AESIs) are defined for this protocol as injection site reactions (including pruritus, erythema, swelling).

    Measured: 34 weeks (SAOL + RW phases)

  20. Disease Reactivation Rate

    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)

    Measured: 18 weeks

  21. Treatment Failures

    Treatment failures (i.e. patients who experience at least one disease reactivation) during the SAOL phase

    Measured: 18 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Apr 2017
  2. Study start21 Jul 2017
  3. Primary completion31 Oct 2023
  4. Study completion2 Nov 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Initial phase of 18 weeks is a single arm, open-label (SAOL) period where Tadekinig alfa is administered in addition to the standard of care treatment used for the control of flares. The SAOL period will be followed by an up to 16-week randomized withdrawal phase (RW). All patients who showed response to treatment at the end of the SAOL phase will be enrolled in the RW phase. In the RW phase patients will be randomized to either Tadekinig alfa or placebo.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03113760
Sponsor's protocol ID
NLRC4/XIAP.2016.001
Status last verified
Jun 2025
First submitted
28 Feb 2017
Last updated
2 Jul 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided: This information will be provided soon

Publications

  • Krei JM, Moller HJ, Larsen JB. The role of interleukin-18 in the diagnosis and monitoring of hemophagocytic lymphohistiocytosis/macrophage activation syndrome - a systematic review. Clin Exp Immunol. 2021 Feb;203(2):174-182. doi: 10.1111/cei.13543. Epub 2020 Nov 23.

    PubMed 33128796

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tadekinig alfa and 0.9% sodium chloride in people with NLRC4-MAS and XIAP Deficiency, run by AB2 Bio Ltd. at 9 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Canada, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Prevention of Flares (time frame: 16 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03113760, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2025.

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