Study of ATI-450 in Patients With Cryopyrin-Associated Periodic Syndrome (CAPS)
Condition: Cryopyrin-Associated Periodic Syndrome
MeSH terms: Cryopyrin-Associated Periodic Syndromes; Syndrome
Intervention: ATI-450
Intervention description: Oral, small molecule MK2 inhibitor
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Open-label, single-arm study
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cryopyrin-Associated Periodic Syndrome; CAPS

Summary:

      This is a Phase 2 study to investigate the safety and efficacy of ATI-450 for the Maintenance
      of Remission in Patients with Cryopyrin-Associated Periodic Syndrome (CAPS) Previously
      Managed with Anti-IL-1 Therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or
             Neonatal Onset Multisystem Inflammatory Disease. Prior agreement between the
             Investigator and Aclaris for study eligibility is required for patients who do not
             have a molecular diagnosis of NALP3 mutations available (either testing not performed,
             or testing performed, but negative) upon study entry. For those patients who have not
             been molecularly tested for NALP3 mutations, molecular testing should be performed
             during the study.

          -  Patients with a PGA score of "minimal" or less and hsCRP and SAA values within the
             normal range (≤10mg/L), and who are considered to have achieved that response as a
             result of successful anti-IL-1 therapy.

          -  Continuous Treatment with anti-IL1 therapy for at least 6 months.

          -  Able to understand and comply with study procedures and able to provide informed
             consent.

          -  Male or non-pregnant, non-nursing female patients at least 18 years of age, inclusive.

               -  Female patients who are of childbearing potential must use 2 methods of highly
                  effective contraception* - one of which must be a physical barrier- for the
                  duration of the study and for 30 days after the last dose.

               -  Male patients of childbearing potential with a female partner of childbearing
                  potential must agree to use a condom plus another highly effective form of birth
                  control for the duration of the study and for 90 days after the last dose.

          -  Female patients must have a negative serum pregnancy test at screening and a negative
             urine pregnancy test prior to dosing on Day 1.

          -  Willing and capable of taking appropriate Covid-19 risk mitigation precautions (e.g.
             wearing a mask in public, adhering to social distancing, etc.) as required by local,
             state, or federal guidelines during participation in the study.

        Exclusion Criteria:

          -  Participation in any clinical study with an investigative agent within 12 weeks prior
             to entry or within 5 half-lives of the investigational agent.

          -  Being treated with another immuno-suppressive agent (i.e., in addition to an anti-IL-1
             product) for CAPS syndrome (anti- IL-1 therapy will have been used for at least 6
             months and will be stopped at study entry).

          -  Use of any of the following treatments within the indicated washout period prior to
             the baseline visit:

               -  Systemic immunosuppressant or immunomodulatory therapy (e.g., etanercept,
                  alefacept, infliximab, methotrexate) within 16 weeks prior to Visit 2 (excluding
                  anti- IL-1 therapy for CAPS).

               -  Janus Kinase (JAK) inhibitors (systemic or topical) within 4 weeks prior to Visit
                  2.

               -  Systemic corticosteroids within 4 weeks prior to Visit 2 (Intranasal, inhaled,
                  and topical ocular corticosteroids are allowed).

          -  History of being immunocompromised, including a positive HIV at screening (ELISA and
             Western blot) test result. [Previous treatment with anti-IL1 therapy is not an
             exclusion]

          -  A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody test result.

          -  Live vaccinations within 3 months prior to the start of the trial, or during the
             trial.

          -  History of recurrent and/or evidence of active bacterial, fungal, or viral infections.

          -  History or evidence of active or latent tuberculosis (TB).

          -  Tests performed at a central laboratory at screening that meet any of the criteria
             below (out of range labs may be rechecked one time, after consultation with sponsor or
             designee, before patient is considered a screen failure):

               -  White blood cell (WBC) count <3.0×103 cells/mm3

               -  Absolute neutrophil count (ANC) <1.5×103 cells/mm3

               -  Lymphocyte count <0.5×103 cells/mm3

               -  Platelet count <100×103 cells/mm3

               -  Hemoglobin <10 g/dL

               -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 2×upper
                  limit of normal (ULN)

               -  Total bilirubin level >2×ULN, unless patient has been diagnosed with Gilberts'
                  disease and this is clearly documented

               -  Estimated glomerular filtration rate Estimated glomerular filtration rate (eGFR),
                  <40 mL/min/1.73m2 based on Modification of Diet and Renal Disease formula

          -  Any clinically significant laboratory abnormality that would affect interpretation of
             study data or safety of the patient's participation in the study, per the judgment of
             the investigator.

          -  Patient has clinically significant abnormal findings other than CAPS from physical
             examination that may affect the interpretation of study data or the safety of the
             patient's participation in the study, per the judgment of the investigator.

          -  Patient has a clinically important history of a medical disorder that would compromise
             patient safety or data quality, per the judgement of the investigator.

          -  Blood pressure (BP) levels (in supine position after at least 5 minutes rest): <90
             mmHg or >140 mmHg for systolic BP or <40 mmHg or >90 mmHg for diastolic blood
             pressure.

          -  Patients with history of stroke.

          -  Significant cardiac disease that would affect interpretation of study data or the
             safety of the patient's participation in the study, per the judgment of the
             investigator, including recent myocardial infarction or unstable angina, or heart
             failure with New York Heart Association Class III or IV symptoms.

          -  Patients with the following screening or pre-dose ECG findings, specifically:

               -  Evidence of atrial fibrillation, atrial flutter, complete right or left bundle
                  branch block, Wolff-Parkinson-White Syndrome, or other significant rhythm
                  disturbance

               -  Evidence of acute ischemia

               -  Screening or pre-dose baseline mean QTcF >450 msec for males or >470 msec for
                  females (use of the ECG algorithm is acceptable for this purpose)

               -  Personal or family history of congenital long QT syndrome or sudden death

               -  Any other finding that is considered clinically significant

          -  A confirmed diagnosis of Covid-19 at baseline or at any time during the study.