Open-label Extension Study with Tadekinig Alfa (r-hIL-18BP) to Monitor Safety and Tolerability in Patients with IL-18 Driven Monogenic Autoinflammatory Conditions: NLRC4 Mutation and XIAP Deficiency
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 11
- Locations
- 11
- Primary Endpoint
- Reports of abnormal laboratory results
Study Overview
Brief Summary
This is an open-label extension study for patients previously enrolled in the AB2 Bio Ltd. ongoing Phase III clinical trial NLRC4/XIAP.2016.001 (IND N° 127953). This OLE study will evaluate the long-term safety and tolerability of Tadekinig alfa in patients suffering from pediatric monogenic autoinflammatory diseases harboring deleterious mutations of NLRC4 and XIAP.
Detailed Description
Pediatric auto-inflammatory conditions related to spontaneous activating mutations of the NLRC4 and with recurrent MAS-like flares with constitutive IL-18 hypersecretion, may require long-term blockade of the IL-18 pathway.
Patients with X-linked inhibitor of apoptosis (XIAP) deficiency and suffering from Hemophagocytic-Lymphohistiocytosis (HLH), a MAS-like syndrome, also show high levels of serum IL-18 and may benefit from IL-18 blockade treatment until a curative hematopoietic stem cell transplantation can be performed The safety of IL-18 blockade during long-term periods is of major interest for the treatment of these patients
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •(both criteria must be met)
- •Patients have participated in AB2 Bio ltd. Phase III clinical trial NLRC4/XIAP.2016.001 (IND N° 127953) 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. Or b) Patients that completed the first 18-week RCT phase and completed the RW phase of the preceding clinical trial. Or 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
- •Women of childbearing potential with negative urine pregnancy test (UPT) at all visits
Exclusion Criteria
- •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
- •Evidence or history of malignancy
- •Evidence of invasive or life-threatening infection
- •History of tuberculosis
- •Life-threatening bleeding within 2 weeks of screening
- •Vaccination with a live vaccine within the previous 3 months
- •Evidence of severe organ compromise including but not limited to: (see details in the protocol)
- •Pregnant or breastfeeding females
- •Inability to follow highly effective birth control recommendations during the study and until 1 month after the end of the treatment.
- •Inability to provide informed consent, and also assent if applicable
- •Life expectancy less than 4 weeks
- •Concomitant use of other immunosuppression except NSAIDs, glucocorticoids, cyclosporine, tacrolimus, IL-1 inhibitors (Anakinra, Canakinumab, or Rilonacept)
Arms & Interventions
Tadekinig alfa
Active drug treatment during 26 weeks
Intervention: Tadekinig alfa (Drug)
Outcomes
Primary Outcomes
Reports of abnormal laboratory results
Time Frame: 26 weeks
Report of clinically significant abnormal laboratory results (i.eSerum CRP (ug/mL), Serum Ferritin (ng/mL). and any other abnormal lab results
Immunogenicity evaluation
Time Frame: 26 weeks
Generation of anti-recombinant human Interleukin-18 Binding Protein (anti-rhIL-18BP) antibodies
Evaluation of the local tolerability at the injection site
Time Frame: 26 weeks
Evaluation will be done based on the Local Tolerability Index where the patients will be asked to assess the degree of pain, redness, swelling, bruising, tenderness and itching, they are experiencing from each injection.
Reports of adverse events
Time Frame: 26 weeks
The incidence, nature and severity of AEs will be reported
Reports of abnormal physical examination
Time Frame: 26 weeks
Measurements will be done using the modified Auto-inflammatory Disease Activity Index (mAIDAI) including multiple measurements aggregated as 1 / 0.
Secondary Outcomes
No secondary outcomes reported