Pilot Study of Dapansutrile Capsules in Schnitzler's Syndrome
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|ClinicalTrials.gov Identifier: NCT03595371|
Recruitment Status : Recruiting
First Posted : July 23, 2018
Last Update Posted : July 6, 2021
|Condition or disease||Intervention/treatment||Phase|
|Schnitzler Syndrome||Drug: dapansutrile||Phase 2|
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).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||May 15, 2018|
|Estimated Primary Completion Date :||December 30, 2022|
|Estimated Study Completion Date :||February 28, 2023|
Experimental: dapansutrile capsules
Hard gelatin capsules containing 100 mg of dapansutrile (API)
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.
Other Name: OLT1177 capsules
- Schnitzler's Syndrome Symptom Index [ Time Frame: Day 14 ]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".
- Physical Examination [ Time Frame: Day 14 ]A full or targeted physical examination of the patient's major body systems
- Vital signs - pulse [ Time Frame: Day 14 ]Pulse will be recorded and analyzed for changes.
- Vital signs - temperature [ Time Frame: Day 14 ]Body temperature will be recorded and analyzed for changes.
- Vital signs - respirations [ Time Frame: Day 14 ]Respiration rate will be recorded and analyzed for changes.
- Vital signs - blood pressure [ Time Frame: Day 14 ]Systolic and diastolic blood pressure will be recorded and analyzed for changes.
- Safety laboratory measures - chemistry markers [ Time Frame: Day 14 ]Blood samples will be drawn and analyzed for chemistry blood markers.
- Safety laboratory measures - hematology/complete blood count [ Time Frame: Day 14 ]Blood samples will be drawn and a complete blood count will be performed.
- Safety laboratory measures - urinalysis [ Time Frame: Day 14 ]Urine samples will be collected and analyzed.
- Adverse events [ Time Frame: Up to 42 days ]Adverse events will be described with respect to seriousness, intensity, relationship to treatment, action taken and outcome of the event.
- Photographs of posterior torso [ Time Frame: Day 14 ]Photographs of posterior torso or other non-identifying areas of the body displaying urticarial rash.
- Investigator Global Assessment of Disease Activity [ Time Frame: Later of Day 14 or symptom relapse (expected no later than Day 28) ]One general question the Investigator is asked to answer about the overall perceived status of the subject's symptoms.
- Subject Global Assessment of Disease Activity [ Time Frame: Later of Day 14 or symptom relapse (expected no later than Day 28) ]Overall assessment of disease activity in response to the question: Please note on this scale (0=bad; 10=outstanding) how you are feeling.
- Subject Skin Assessment [ Time Frame: Later of Day 14 or symptom relapse (expected no later than Day 28) ]Extent of urticaria on subject's body.
- Time to relapse of SchS Symptoms after cessation of dapansutrile [ Time Frame: Later of Day 14 or symptom relapse (expected no later than Day 28) ]Time to the emergence of Grade 2 or higher SchS symptoms
- Subject Global Evaluation of Treatment [ Time Frame: Later of Day 14 or symptom relapse (expected no later than Day 28) ]Two general questions the subject is asked to answer about the overall perceived quality of the investigational product.
- Plasma concentrations of dapansutrile [ Time Frame: Later of Day 14 or symptom relapse (expected no later than Day 28) ]Blood samples analyzed for levels of dapansutrile.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03595371
|Contact: Robert Barrow||+1 firstname.lastname@example.org|
|Nijmegen, Netherlands, 6525 GA|
|Contact: Ruud Raijmakers, MD|
|Principal Investigator: Anna Simon, MD, PhD|
|Sub-Investigator: Ruud Raijmakers, MD|
|Study Chair:||Curt Scribner, MD||Olatec Therapeutics LLC|