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Study of ATI-450 in Patients With Cryopyrin-Associated Periodic Syndrome (CAPS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04524858
Recruitment Status : Recruiting
First Posted : August 24, 2020
Last Update Posted : November 27, 2020
Sponsor:
Information provided by (Responsible Party):
Aclaris Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE August 19, 2020
First Posted Date  ICMJE August 24, 2020
Last Update Posted Date November 27, 2020
Actual Study Start Date  ICMJE October 23, 2020
Estimated Primary Completion Date May 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 21, 2020)
Assess the safety and tolerability of ATI-450 to maintain remission in patients with CAPS previously managed with anti-IL-1 therapy: Adverse Events (AEs) [ Time Frame: Baseline to week 12 ]
Adverse Events (AEs) will be coded with the Medical Dictionary for Regulatory Activities (MedDRA). AEs will be presented by system organ class and preferred term in frequency tables.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 25, 2020)
  • Total Number of participants who maintain disease remission (hsCRP) [ Time Frame: Baseline to week 12 ]
    Remission is defined as a high sensitivity C-reactive protein (hsCRP) within normal range (≤10 mg/L).
  • Total Number of participants who maintain disease remission (SAA) [ Time Frame: Baseline to week 12 ]
    Remission is defined as a serum amyloid A (SAA) value within the normal range (≤10 mg/L).
  • Total number of participants who maintain disease remission (PGA) [ Time Frame: Baseline to week 12 ]
    Remission is defined as a Physician Global Assessment (PGA) score of absent or minimal. The Physician's Global Assessment of Autoinflammatory Disease Activity (PGA) is a measure to be completed by the investigator or designee. The PGA uses a 5-point rating scale: absent, minimal, mild, moderate, and severe. The investigator will select a rating based on the patient's current disease activity at the time of the visit. Lower PGA scores represent better outcomes.
  • Time to relapse [ Time Frame: Baseline to week 12 ]
    Relapse is defined as a two-point worsening on the PGA scale. The Physician's Global Assessment of Autoinflammatory Disease Activity (PGA) is a measure to be completed by the investigator or designee. The PGA uses a 5-point rating scale: absent, minimal, mild, moderate, and severe. The investigator will select a rating based on the patient's current disease activity at the time of the visit. Lower PGA scores represent better outcomes.
  • Total number of participants who experience re-emergence of disease symptoms after discontinuation of ATI-450 [ Time Frame: Follow-up day 1 to follow-up day 7 ]
    Re-emergence is defined as a daily Key Symptom Score (KSS) ≥ 3 points higher than baseline for at least 2 consecutive days. The KSS is derived from the patient-administered DHAF, and is the average on a 0 to 10 scale (0 = None, 10 = Very Severe) of 5 separate scales - rash, feeling of fever and chills, joint pain, eye redness and pain, and fatigue. Lower KSS scores represent better outcomes.
  • Total number of participants with a mean KSS no more than 2 points higher than baseline for at least 6 out of 8 weeks during the treatment period [ Time Frame: Baseline to week 12 ]
    Key Symptom Score (KSS). The KSS is derived from the patient-administered DHAF, and is the average on a 0 to 10 scale (0 = None, 10 = Very Severe) of 5 separate scales - rash, feeling of fever and chills, joint pain, eye redness and pain, and fatigue. Lower KSS scores represent better outcomes.
  • Change from baseline in PGA [ Time Frame: Baseline to week 12 ]
    Physician Global Assessment (PGA). The Physician's Global Assessment of Autoinflammatory Disease Activity (PGA) is a measure to be completed by the investigator or designee. The PGA uses a 5-point rating scale: absent, minimal, mild, moderate, and severe. The investigator will select a rating based on the patient's current disease activity at the time of the visit. Lower PGA scores represent better outcomes.
  • Change from baseline in KSS [ Time Frame: Baseline to week 12 ]
    Key Symptom Score (KSS). The KSS is derived from the patient-administered DHAF, and is the average on a 0 to 10 scale (0 = None, 10 = Very Severe) of 5 separate scales - rash, feeling of fever and chills, joint pain, eye redness and pain, and fatigue. Lower KSS scores represent better outcomes.
  • Change from baseline in CRP [ Time Frame: Baseline to week 12 ]
    C-reactive protein (CRP). CRP values ≤10 mg/L are considered normal range.
  • Change from baseline in SAA [ Time Frame: Baseline to week 12 ]
    serum amyloid A (SAA). SAA values ≤10 mg/L are considered normal range.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 21, 2020)
  • Total Number of participants who maintain disease remission (hsCRP) [ Time Frame: Baseline to week 12 ]
    Remission is defined as a high sensitivity C-reactive protein (hsCRP) within normal range (≤10 mg/L).
  • Total Number of participants who maintain disease remission (SAA) [ Time Frame: Baseline to week 12 ]
    Remission is defined as a serum amyloid A (SAA) value within the normal range (≤10 mg/L).
  • Total number of participants who maintain disease remission (PGA) [ Time Frame: Baseline to week 12 ]
    Remission is defined as a Physician Global Assessment (PGA) score of absent or minimal. Lower PGA scores represent better outcomes.
  • Time to relapse [ Time Frame: Baseline to week 12 ]
    Relapse is defined as a two-point worsening on the PGA scale. Lower PGA scores represent better outcomes.
  • Total number of participants who experience re-emergence of disease symptoms after discontinuation of ATI-450 [ Time Frame: Follow-up day 1 to follow-up day 7 ]
    Re-emergence is defined as a daily Key Symptom Score (KSS) ≥ 3 points higher than baseline for at least 2 consecutive days. KSS is derived from the patient-administered daily health assessment form (DHAF). Lower KSS scores represent better outcomes.
  • Total number of participants with a mean KSS no more than 2 points higher than baseline for at least 6 out of 8 weeks during the treatment period [ Time Frame: Baseline to week 12 ]
    Key Symptom Score (KSS). Lower KSS scores represent better outcomes.
  • Change from baseline in PGA [ Time Frame: Baseline to week 12 ]
    Physician Global Assessment (PGA). Lower PGA scores represent better outcomes.
  • Change from baseline in KSS [ Time Frame: Baseline to week 12 ]
    Key Symptom Score (KSS). Lower KSS scores represent better outcomes.
  • Change from baseline in CRP [ Time Frame: Baseline to week 12 ]
    C-reactive protein (CRP). CRP values ≤10 mg/L are considered normal range.
  • Change from baseline in SAA [ Time Frame: Baseline to week 12 ]
    serum amyloid A (SAA). SAA values ≤10 mg/L are considered normal range.
Current Other Pre-specified Outcome Measures
 (submitted: August 21, 2020)
  • Change from baseline in serum cytokines IL-1β [ Time Frame: Baseline to week 12 ]
    Exploratory endpoint to assess the change from baseline in serum cytokines IL-1β ATI-450 in patients with CAPS.
  • Change from baseline in serum cytokines IL-1α [ Time Frame: Baseline to week 12 ]
    Exploratory endpoint to assess the change from baseline in serum cytokines IL-1α of ATI-450 in patients with CAPS.
  • Change from baseline in serum cytokines IL-6 [ Time Frame: Baseline to week 12 ]
    Exploratory endpoint to assess the change from baseline in serum cytokines IL-6 of ATI-450 in patients with CAPS.
  • Change from baseline in serum cytokines IL-18 [ Time Frame: Baseline to week 12 ]
    Exploratory endpoint to assess the change from baseline in serum cytokines IL-18 of ATI-450 in patients with CAPS.
  • Change from baseline in serum cytokines TNF-α [ Time Frame: Baseline to week 12 ]
    Exploratory endpoint to assess the change from baseline in serum cytokines TNF-α of ATI-450 in patients with CAPS.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Study of ATI-450 in Patients With Cryopyrin-Associated Periodic Syndrome (CAPS)
Official Title  ICMJE A Phase 2a, Open-Label, Single-Arm 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
Brief 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.
Detailed Description This is a Phase 2a, Open-Label, Single-Arm 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. The study will consist of up to an 8-week screening period, a 12-week treatment period, and a 4-week safety follow-up period. The total duration of the study for patients remaining until their final follow-up assessment will be up to 24 weeks.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Open-label, single-arm study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cryopyrin-Associated Periodic Syndrome
Intervention  ICMJE Drug: ATI-450
Oral, small molecule MK2 inhibitor
Study Arms  ICMJE Experimental: ATI-450
Oral, small molecule MK2 inhibitor will be administered twice daily (BID) at a dose of 50 mg
Intervention: Drug: ATI-450
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 21, 2020)
10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 1, 2021
Estimated Primary Completion Date May 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Nicholas Hebel (484) 540-6247 nhebel@aclaristx.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04524858
Other Study ID Numbers  ICMJE ATI-450-CAPS-201
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Aclaris Therapeutics, Inc.
Study Sponsor  ICMJE Aclaris Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: David Gordon Aclaris Therapeutics
PRS Account Aclaris Therapeutics, Inc.
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP