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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
Sponsor:
Collaborator:
Radboud University
Information provided by (Responsible Party):
Olatec Therapeutics LLC

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Schnitzler Syndrome Drug: dapansutrile Phase 2

Detailed Description:

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
Experimental: dapansutrile capsules
Hard gelatin capsules containing 100 mg of dapansutrile (API)
Drug: dapansutrile
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




Primary Outcome Measures :
  1. 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".


Secondary Outcome Measures :
  1. Physical Examination [ Time Frame: Day 14 ]
    A full or targeted physical examination of the patient's major body systems

  2. Vital signs - pulse [ Time Frame: Day 14 ]
    Pulse will be recorded and analyzed for changes.

  3. Vital signs - temperature [ Time Frame: Day 14 ]
    Body temperature will be recorded and analyzed for changes.

  4. Vital signs - respirations [ Time Frame: Day 14 ]
    Respiration rate will be recorded and analyzed for changes.

  5. Vital signs - blood pressure [ Time Frame: Day 14 ]
    Systolic and diastolic blood pressure will be recorded and analyzed for changes.

  6. Safety laboratory measures - chemistry markers [ Time Frame: Day 14 ]
    Blood samples will be drawn and analyzed for chemistry blood markers.

  7. Safety laboratory measures - hematology/complete blood count [ Time Frame: Day 14 ]
    Blood samples will be drawn and a complete blood count will be performed.

  8. Safety laboratory measures - urinalysis [ Time Frame: Day 14 ]
    Urine samples will be collected and analyzed.

  9. 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.

  10. Photographs of posterior torso [ Time Frame: Day 14 ]
    Photographs of posterior torso or other non-identifying areas of the body displaying urticarial rash.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.


Other Outcome Measures:
  1. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female subjects 18 years old or older
  2. Prior diagnosis of Schnitzler's syndrome
  3. 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
  4. Grade 0 SchS symptoms at the Screening/Baseline visit
  5. 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
  6. 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:

  1. Pregnant, nursing or intent to become pregnant during the study
  2. Not responsive or well controlled by anakinra therapy for at least 6 weeks prior to the Screening/Baseline visit
  3. 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)
  4. Active infection within 3 days prior to the Screening/Baseline visit
  5. History of or known positive for HIV, Hepatitis B surface antigen (HBsAg) or antibodies to Hepatitis C Virus (HCV)
  6. 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
  7. 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
  8. 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

Information from the National Library of Medicine

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


Contacts
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Contact: Robert Barrow +1 833-652-8321 inquiries@olatec.com

Locations
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Netherlands
Radboudumc Recruiting
Nijmegen, Netherlands, 6525 GA
Contact: Ruud Raijmakers, MD         
Principal Investigator: Anna Simon, MD, PhD         
Sub-Investigator: Ruud Raijmakers, MD         
Sponsors and Collaborators
Olatec Therapeutics LLC
Radboud University
Investigators
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Study Chair: Curt Scribner, MD Olatec Therapeutics LLC
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Responsible Party: Olatec Therapeutics LLC
ClinicalTrials.gov Identifier: NCT03595371    
Other Study ID Numbers: OLT1177-07
First Posted: July 23, 2018    Key Record Dates
Last Update Posted: July 6, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Olatec Therapeutics LLC:
Schnitzler
Additional relevant MeSH terms:
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Schnitzler Syndrome
Syndrome
Disease
Pathologic Processes
Monoclonal Gammopathy of Undetermined Significance
Paraproteinemias
Immunoproliferative Disorders
Immune System Diseases
Dapansutrile
Anti-Inflammatory Agents