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
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 15
- Locations
- 9
- Primary Endpoint
- Prevention of Flares
Study Overview
Brief 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 (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.
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)
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Tadekinig alfa
Patients that showed response to treatment in the SAOL phase will receive Tadekinig alfa for up to 16 weeks.
Intervention: Tadekinig alfa (Drug)
0.9% sodium chloride
Patients that showed response to treatment in the SAOL phase will receive placebo comparator for up to 16 weeks.
Intervention: 0.9% sodium chloride (Other)
Outcomes
Primary Outcomes
Prevention of Flares
Time Frame: 16 weeks
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.
Secondary Outcomes
- Improvement in Laboratory Markers - Erythrocyte Sedimentation Rate(18 weeks)
- Hospital Length of Stay(34 weeks)
- Change in Physician Global Assessment (PGA)(34 weeks)
- Local Tolerability at the Injection Site (as Defined by Number of Participants With Adverse Events of Special Interest)(34 weeks (SAOL + RW phases))
- Best Response(18 weeks)
- Improvement in Laboratory Markers - Hemoglobin(18 weeks)
- Improvement in Laboratory Markers - Fibrinogen(18 weeks)
- Improvement in Laboratory Markers - D-Dimer(18 weeks)
- Immunogenicity Evaluation(34 weeks (SAOL + RW phases))
- Duration of Response During the SAOL Phase (Until End of Phase or Disease Reactivation)(The actual mean treatment duration in the SAOL phase was 17.6 weeks (minimum / maximum 5.9 / 22.1 weeks).)
- Change From Baseline in mAIDAI Total Score in the SAOL Phase(18 weeks)
- Change From Baseline in Serum Ferritin(34 weeks)
- Change From Baseline in Serum CRP(34 weeks)
- Improvement in Laboratory Markers - Albumin(18 weeks)
- Disease Reactivation Rate(18 weeks)
- Treatment Failures(18 weeks)
- Resolution of Fevers, Hepato/Splenomegaly and Skin Rash(18 weeks)
- Improvement in Laboratory Markers - AST (SGOT)(18 weeks)
- Improvement in Laboratory Markers - ALT (SGPT)(18 weeks)
- Improvement in Laboratory Markers - Platelets(18 weeks)
- Change in Patient/Caregiver Qualitative Evaluation of Health Status in Randomized Withdrawal Phase(16 weeks)