Clinical trial NCT03512314: Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency As Open Label Extension
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: XIAP Deficiency
NLRC4-MAS
Lead sponsor: AB2 Bio Ltd.
Sponsor class: INDUSTRY
First posted: 2018-04-30
Enrollment: 11
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: Inclusion Criteria: (both criteria must be met)

1. 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
2. Women of childbearing potential with negative urine pregnancy test (UPT) at all visits

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: (see details in the protocol)
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)

Primary outcomes:
measure: Reports of adverse events
timeFrame: 26 weeks
measure: Reports of abnormal physical examination
timeFrame: 26 weeks
measure: Reports of abnormal laboratory results
timeFrame: 26 weeks
measure: Immunogenicity evaluation
timeFrame: 26 weeks
measure: Evaluation of the local tolerability at the injection site
timeFrame: 26 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UCSD _ Department of Pediatrics / Rady Children's Hospital
state: California
city: Gainsville
country: United States
facility: Shands Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta at Egleston
state: Georgia
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital _ Baylor College of Medicine
state: Texas
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Montréal
country: Canada
facility: CHU Sainte-Justine
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg, Centrum für Chronische Immundefizienz (CCI) - Paediatric Unit
state: Baden-Württemberg
Study officials:
affiliation: Children Hospital of Philadelphia
name: Eduard Behrens, MD
role: PRINCIPAL_INVESTIGATOR
References: