NLRC4 mutation XIAP deficiency
Conditions
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 de
Sponsors
AB2 Bio Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients have participated in the preceding clinical trial NLRC4/XIAP.2016.001 (IND N° 127953 _ EudraCT number: 2018-003297-27) 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. b. Patients that completed the first 18-week RCT phase and completed the RW phase of the preceding clinical trial. 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. The time period between participation in the RCT or RW and the OLE study should not exceed 3 months. After this period, patients are no longer eligible for enrollment into the OLE study. 2. 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) is 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 Are the trial subjects under 18? yes Number of subjects for this age range: 10 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. 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 2. Evidence or history of malignancy 3. Evidence of invasive or life-threatening infection 4. History of tuberculosis 5. Life-threatening bleeding within 2 weeks of screening 6. Vaccination with a live vaccine within the previous 3 months 7. Evidence of severe organ compromise including but not limited to: ? Intractable encephalopathy, psychosis, or seizures ? Creatinine of > 2X ULN (patients receiving dialysis are also excluded) ? Albumin 10x ULN, or evidence of acute liver failure ? Mechanical ventilation (including invasive and non-invasive forms) ? Heart failure requiring medical support including medications ? Hypotension from any cause requiring the use of vasopressors 8. Pregnant or breastfeeding females 9. Inability to follow highly effective birth control recommendations during the study and until 1 month after the end of the treatment. 10. Inability to provide informed consent, and also assent if applicable 11. Life expectancy less than 4 weeks 12. Concomitant use of other immunosuppression except NSAIDs, glucocorticoids, cyclosporine, tacrolimus, IL-1 inhibitors (Anakinra, Canakinumab, or Rilonacept) 13. Hypersensitivity to the active substance or one of the excipients of the investigational product
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This is an open-label extension study for patients previously enrolled in the preceding clinical trial NLRC4/XIAP.2016.001 (IND N° 127953 _ EudraCT number: 2018-003297-27) to evaluate the long-term safety and tolerability of TA in patients suffering from pediatric monogenic autoinflammatory diseases harboring deleterious mutations of NLRC4 and XIAP ;Secondary Objective: Not applicable;Primary end point(s): - Reports of adverse events: The incidence, nature and severity of AEs will be reported. Reports will be produced according to the MedDRA highest hierarchy / System Organ Class, by MedDRA Preferred Term, by relationship to Tadekinig alfa and by Common Terminology Criteria for Adverse Events (CTCAE)/severity. - Abnormal physical examination: body temperature, hepatosplenomegaly, and presence of skin rash. - Abnormal Laboratory results: Including CRP, ferritin, fibrinogen, D-dimer, and any clinically significant abnormal laboratory results. All clinically significant abnormal laboratory results or assessments must be followed until they resolve (return to normal or baseline values) or stabilize, or until they are judged by the Investigator to be no longer clinically significant. - Immunogenicity evaluation: Generation of anti-recombinant human Interleukin-18 Binding Protein (anti-rhIL-18BP) antibodies - Local tolerability at the injection site (evaluated by a standardized assessment) ;Timepoint(s) of evaluation of this end point: 26 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable | — |
Countries
Canada, Germany, United States
Contacts
Public ContactEduardo Schiffrin
AB2 Bio Ltd.
Outcome results
None listed