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.

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.

Laboratory measure

Laboratory measure

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.

Change from Baseline mean value to Week 18 mean value

Change from Baseline mean value to Week 18 mean value

Change from Baseline mean value to Week 18 mean value

Change from Baseline mean value to Week 18 mean value

Change from Baseline mean value to Week 18 mean value

Change from Baseline mean value to Week 18 mean value

Change from Baseline mean value to Week 18 mean value

Change from Baseline mean value to Week 18 mean value

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

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.

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.

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

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

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)

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

Total of all reporting groups

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.

The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan. 1 patient treated with Placebo in the first treatment phase under the initial protocol design starting with a randomized treatment phase is excluded from the efficacy analysis due to the difference in treatment schedule but included in the safety analysis.

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.

The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan. 1 patient treated with Placebo in the first treatment phase under the initial protocol design starting with a randomized treatment phase is excluded from the efficacy analysis due to the difference in treatment schedule but included in the safety analysis.

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.

Change from Baseline to Week 18 in mAIDAI Total Score. The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan. 1 patient treated with Placebo in the first treatment phase under the initial protocol design starting with a randomized treatment phase is excluded from the efficacy analysis due to the difference in treatment schedule but included in the safety analysis.

Laboratory measure

Values indicate change from Baseline to End of Phase results. The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan. 1 patient treated with Placebo in the first treatment phase under the initial protocol design starting with a randomized treatment phase is excluded from the efficacy analysis due to the difference in treatment schedule but included in the safety analysis.

Laboratory measure

Values indicate change from Baseline to End of Phase results. The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan. 1 patient treated with Placebo in the first treatment phase under the initial protocol design starting with a randomized treatment phase is excluded from the efficacy analysis due to the difference in treatment schedule but included in the safety analysis.

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.

The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan. 1 patient treated with Placebo in the first treatment phase under the initial protocol design starting with a randomized treatment phase is excluded from the efficacy analysis due to the difference in treatment schedule but included in the safety analysis.

Change from Baseline mean value to Week 18 mean value

The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan. 1 patient treated with Placebo in the first treatment phase under the initial protocol design starting with a randomized treatment phase is excluded from the efficacy analysis due to the difference in treatment schedule but included in the safety analysis.

Change from Baseline mean value to Week 18 mean value

The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan. 1 patient treated with Placebo in the first treatment phase under the initial protocol design starting with a randomized treatment phase is excluded from the efficacy analysis due to the difference in treatment schedule but included in the safety analysis.

Change from Baseline mean value to Week 18 mean value

The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan. 1 patient treated with Placebo in the first treatment phase under the initial protocol design starting with a randomized treatment phase is excluded from the efficacy analysis due to the difference in treatment schedule but included in the safety analysis.

Change from Baseline mean value to Week 18 mean value

The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan. 1 patient treated with Placebo in the first treatment phase under the initial protocol design starting with a randomized treatment phase is excluded from the efficacy analysis due to the difference in treatment schedule but included in the safety analysis.

Change from Baseline mean value to Week 18 mean value

The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan. 1 patient treated with Placebo in the first treatment phase under the initial protocol design starting with a randomized treatment phase is excluded from the efficacy analysis due to the difference in treatment schedule but included in the safety analysis.

Change from Baseline mean value to Week 18 mean value

The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan. 1 patient treated with Placebo in the first treatment phase under the initial protocol design starting with a randomized treatment phase is excluded from the efficacy analysis due to the difference in treatment schedule but included in the safety analysis.

Change from Baseline mean value to Week 18 mean value

The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan. 1 patient treated with Placebo in the first treatment phase under the initial protocol design starting with a randomized treatment phase is excluded from the efficacy analysis due to the difference in treatment schedule but included in the safety analysis.

Change from Baseline mean value to Week 18 mean value

The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan. 1 patient treated with Placebo in the first treatment phase under the initial protocol design starting with a randomized treatment phase is excluded from the efficacy analysis due to the difference in treatment schedule but included in the safety analysis.

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

The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan. 1 patient treated with Placebo in the first treatment phase under the initial protocol design starting with a randomized treatment phase is excluded from the efficacy analysis due to the difference in treatment schedule but included in the safety analysis.

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.

The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan. 1 patient treated with Placebo in the first treatment phase under the initial protocol design starting with a randomized treatment phase is excluded from the efficacy analysis due to the difference in treatment schedule but included in the safety analysis.

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.

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

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

Patients reporting at least one AESI. The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan. 1 patient treated with Placebo in the first treatment phase under the initial protocol design starting with a randomized treatment phase is excluded from the efficacy analysis due to the difference in treatment schedule but included in the safety analysis.

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)

The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan. 1 patient treated with Placebo in the first treatment phase under the initial protocol design starting with a randomized treatment phase is excluded from the efficacy analysis due to the difference in treatment schedule but included in the safety analysis.

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

Treatment failures were defined as patients who experienced at least 1 disease reactivation. Disease reactivation includes full or partial disease reactivation after the first assessment indicating partial or complete response during the SAOL phase as defined in the statistical analysis plan.

The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan.

Response to therapy (including complete response and partial response) in the SAOL phase from Week 10 onwards and observed at least at 2 consecutive visits at least 2 weeks apart during the SAOL phase

The safety and efficacy analyses during the SAOL phase is based on the SAOL-FAS as defined in the study protocol and statistical analysis plan. 1 patient treated with Placebo in the first treatment phase under the initial protocol design starting with a randomized treatment phase is excluded from the efficacy analysis due to the difference in treatment schedule but included in the safety analysis.

The Randomized Double-Blind Placebo-Controlled (RDBPC) Analysis Set includes 1 patient treated with Placebo in the first treatment phase.

The Tadekinig alfa - Randomized Withdrawal Full Analysis Set (RW-FAS) includes all patients who met the criteria for randomization and were randomized to blinded treatment with Tadekinig alfa in the up to 16 weeks randomized withdrawal phase, which follows the SAOL phase.

The Placebo - Randomized Withdrawal Full Analysis Set (RW-FAS) includes all patients who met the criteria for randomization and were randomized to blinded treatment with Placebo in the up to 16 weeks randomized withdrawal phase, which follows the SAOL phase.

Time from informed consent signature up to day prior to first dose of study treatment