Pilot Study of Dapansutrile Capsules in Schnitzler's Syndrome

Study Overview
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Brief Summary
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This is a pilot, open-label Phase 2, single-center, repeat dose, single cohort, proof-of-concept, safety, pharmacodynamics and efficacy study of dapansutrile capsules to be conducted in subjects with Schnitzler's syndrome (SchS) currently well controlled by anakinra therapy. At least 5 but no more than 10 subjects will be enrolled.

Detailed Description
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Subjects who are currently taking and responsive to anakinra (Kineret®) for at least 6 weeks will be screened for eligibility at the Screening / Baseline (Day 1) visit. Following confirmation of eligibility, subjects will be enrolled, the first dose of dapansutrile will be administered at the clinical site and safety and efficacy assessments will be completed. Subjects will self-administer dapansutrile twice a day by mouth for 14 consecutive days. Subjects will continue their standard dose of anakinra for Days 1, 2 and 3 of the 14-day Treatment Period and will then cease taking anakinra. At the end of the 14-day Treatment Period subjects will remain off all medication for Schnitzler's syndrome and at the first signs of a relapse or worsening of SchS symptoms, subjects will visit the study clinic for the Symptom Onset visit (SOV) to determine with the Investigator when injections of anakinra should be resumed. In addition, subjects will return to the study clinic on Days 5, 9, 14, 15,16, 18 and 21 for follow-up visits1 and will be contacted by telephone on Day 42 (± 3 Days) for additional follow-up. The Day 15 (± 1 day), Day 16 (± 1 day) and Day 18 (± 1 day) visits will only occur if anakinra therapy has not yet been resumed. Subjects will be given the option to remain in the Nijmegen area after the Day 14 visit and return to the study clinic for the Day 15, 16 and 18 follow-up visits. Alternatively, subjects will be given the option to have these visits conducted at their home by a trained study nurse. Safety assessments will be conducted at each visit and subjects will capture the frequency and intensity of symptoms, including body temperature, using a paper diary. Safety and tolerability will be evaluated by monitoring the occurrence of adverse events (AEs) and changes in abbreviated physical examination findings, vital signs and clinical safety laboratory test results (chemistry, hematology and urinalysis) and inflammatory biomarkers. Clinical activity will be evaluated by: Subject Diary (completed daily), Subject Global Assessment of Disease Activity, Investigator Global Assessment of Disease Activity, and analysis of biomarkers of inflammation, including changes in C-reactive protein (CRP). Daily diary assessments will be captured starting at the Screening / Baseline (Day 1) visit and will continue until Symptom Onset visit or Day 21 visit (whichever occurs latest).

Official Title
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A Pilot, Open-Label, Phase 2, Single-Center, Repeat Dose, Proof- Of-Concept Safety, Pharmacodynamics and Efficacy Study of Orally Administered Dapansutrile Capsules in Subjects With Schnitzler's Syndrome

Conditions
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Schnitzler Syndrome

Intervention / Treatment
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* Drug: dapansutrile


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects 18 years old or older Prior diagnosis of Schnitzler's syndrome Presence of Schnitzler's syndrome that is well controlled by and responsive to anakinra for at least 6 weeks prior to the Screening/Baseline visit Grade 0 SchS symptoms at the Screening/Baseline visit Acceptable overall medical condition to be safely enrolled in and to complete the study (with specific regard to cardiovascular, renal and hepatic conditions) in the opinion of the Investigator Ability to provide written informed consent prior to initiation of any study-related procedures, and ability, in the opinion of the Investigator, to understand and comply with all the requirements of the study as outlined in the protocol. Exclusion Criteria: Pregnant, nursing or intent to become pregnant during the study Not responsive or well controlled by anakinra therapy for at least 6 weeks prior to the Screening/Baseline visit Use or planned use of any prohibited concomitant medications/therapies such as immunotherapies or corticosteroids during the study (until relapse and resumption of anakinra injections) Active infection within 3 days prior to the Screening/Baseline visit History of or known positive for HIV, Hepatitis B surface antigen (HBsAg) or antibodies to Hepatitis C Virus (HCV) Any other concomitant medical or psychiatric conditions, including alcohol or substance abuse, diseases or prior surgeries that in the opinion of the Investigator would impair the subject from safely participating in the trial and/or completing protocol requirements Enrollment in any trial and/or use of any investigational product or device within the immediate 30-day period prior to the Screening/Baseline visit Enrollment in any study previously sponsored by Olatec Therapeutics LLC, specifically Study OLT1177-01, Study OLT1177-02, Study OLT1177-03, Study OLT1177-04 or Study OLT1177-05

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dapansutrile capsules<br>Hard gelatin capsules containing 100 mg of dapansutrile (API) | Drug: dapansutrile<br>* 500 mg dapansutrile administered twice daily (with a potential to increase the dosage to 2 g dapansutrile daily) for a duration of up to 14 consecutive days.<br>* Other names: OLT1177 capsules;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Schnitzler's Syndrome Symptom Index | Proportion of subjects with Grade 0 or 1 SchS symptoms at end of treatment. The Schnitzler's Syndrome Symptom Index (SchS Index) is a composite index incorporating the investigator global assessment of disease activity and levels of plasma CRP. The SchS Index is graded on a 0 - 3 scale with 0 being the best score and indicating no symptoms of Schnitzler's syndrome and 3 being the worst score and indicating severe symptoms of Schnitzler's syndrome. | Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical Examination | A full or targeted physical examination of the patient's major body systems | Day 14 | 
| Vital signs - pulse | Pulse will be recorded and analyzed for changes. | Day 14 | 
| Vital signs - temperature | Body temperature will be recorded and analyzed for changes. | Day 14 | 
| Vital signs - respirations | Respiration rate will be recorded and analyzed for changes. | Day 14 | 
| Vital signs - blood pressure | Systolic and diastolic blood pressure will be recorded and analyzed for changes. | Day 14 | 
| Safety laboratory measures - chemistry markers | Blood samples will be drawn and analyzed for chemistry blood markers. | Day 14 | 
| Safety laboratory measures - hematology/complete blood count | Blood samples will be drawn and a complete blood count will be performed. | Day 14 | 
| Safety laboratory measures - urinalysis | Urine samples will be collected and analyzed. | Day 14 | 
| Adverse events | Adverse events will be described with respect to seriousness, intensity, relationship to treatment, action taken and outcome of the event. | Up to 42 days | 
| Photographs of posterior torso | Photographs of posterior torso or other non-identifying areas of the body displaying urticarial rash. | Day 14 | 
| Investigator Global Assessment of Disease Activity | One general question the Investigator is asked to answer about the overall perceived status of the subject's symptoms. | Later of Day 14 or symptom relapse (expected no later than Day 28) | 
| Subject Global Assessment of Disease Activity | Overall assessment of disease activity in response to the question: Please note on this scale (0=bad; 10=outstanding) how you are feeling. | Later of Day 14 or symptom relapse (expected no later than Day 28) | 
| Subject Skin Assessment | Extent of urticaria on subject's body. | Later of Day 14 or symptom relapse (expected no later than Day 28) | 
| Time to relapse of SchS Symptoms after cessation of dapansutrile | Time to the emergence of Grade 2 or higher SchS symptoms | Later of Day 14 or symptom relapse (expected no later than Day 28) | 
| Subject Global Evaluation of Treatment | Two general questions the subject is asked to answer about the overall perceived quality of the investigational product. | Later of Day 14 or symptom relapse (expected no later than Day 28) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schnitzler