Sponsor terminated study

The purpose of this research study is to see if a drug called ritlecitinib is safe and effective for treating chronic spontaneous urticaria (CSU). CSU is hives and itching lasting over six weeks. Ritlecitinib is approved by the Food and Drug Administration (FDA) to treat another condition, but it is not approved for treating CSU. Participation is expected to last 20 weeks and include 7 clinic visits. This study will involve physical examinations, blood tests, looking at and taking pictures of participant's skin and hives, optional skin biopsies, and hearing tests. Eligible participants for this study will take ritlecitinib for 12 weeks and complete a daily diary about their skin and hives. The main risks of being in this study are side effects from ritlecitinib. Less than 1 in 10 people taking ritlecitinib experience diarrhea, acne, hives, rash, inflammation of hair follicles, dizziness, and increased blood levels of creatine phosphokinase (a muscle protein). Participants could also experience a rare but serious side effect, such as shingles, unusual infection, cancer, or blood clot. Benefits of participating in this study include a potential improvement in participant's condition and quality of life. Participating in this study may also help researchers develop new ways of helping future patients.

INCLUSION CRITERIA:

Participants are eligible to be included in the study only if all the following criteria apply:

• Participant has been informed about study procedures and medications and has provided informed consent prior to initiation of any study-specific activities/procedures

• Participant is able to communicate with the investigator, and understands and complies with the requirements of the study

• Age ≥ 18 to ≤ 65 years of age at screening

• Participant has a negative Tuberculin purified protein derivative (PPD) or QuantiFERON TBGold test (QFT) at screening or within the last 12 months.

• Chronic spontaneous urticaria diagnosis ≥ 3 months at the time of screening visit 1

• Diagnosis of CSU inadequately controlled by second-generation H1-antihistamines (sgAH) at enrollment, as defined by the following:

  • The presence of itch and hives for ≥ 6 consecutive weeks at any time prior to screening visit 2 despite current use of an approved dose of H1-antihistamine
  • Urticaria Activity Score over 7 days (UAS7) (range 0-42) ≥ 16 and Hive Severity Score over 7 days (HSS7) (range 0-21) ≥ 8 during the 7 days prior to enrollment

• Participant must have been on or failed a sgAH at approved or increased doses (up to 2 or 4x the approved dose) for treatment of CSU prior to the Baseline visit and must have documented current use on the day of screening visit ○ If participants are currently on a sgAH, they must continue the same dose throughout the trial

EXCLUSION CRITERIA:

Disease Related

• Urticaria is solely due to inducible urticaria
• Active dermatologic diseases (or conditions) other than chronic urticaria, with urticaria wheals or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema (eg, due to C1 inhibitor deficiency)
• Any other active skin disease associated with chronic itching that might influence, in the investigator's opinion, the study evaluations and results (eg, atopic dermatitis, dermatitis herpetiformis, senile pruritus, etc.)

Other Medical Conditions

• History of, or a concurrent, clinically significant illness, medical condition or laboratory abnormality that, in the investigator's opinion, could affect the conduct of the study

• Active immunosuppression by previous (5 x half-lives or 12 weeks, whichever is longer) or current systemic cytotoxic therapies

• Uncontrolled current illness, including, but not limited to the following: Ongoing or active infections requiring intravenous antimicrobials; symptomatic congestive heart failure defined as NYHA class III or IV; unstable angina pectoris within 6 months of study enrollment; history of myocardial infarction, stroke or intracranial hemorrhage within 6 months prior to enrollment; moderate to severe hepatic impairment (Child-Pugh class B or C); psychiatric illness or social situations that would limit compliance with study requirements

• Previous or current cancer, except curatively treated basal or squamous cell carcinoma of the skin, and curatively treated malignant melanoma stage 0-1A with a low risk of recurrence/metastasis as per assessment of the investigator, cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis and T1)

• Known HIV infection

• Infected with Hepatitis B or Hepatitis C viruses

• Participants with history of either untreated or inadequately treated latent or active TB infections/currently being treated for active TB

• Recent (within 21 days before visit 1) major surgery

• Participants who have history of a single episode of disseminated HZ or disseminated HS or recurrent (> 1 episode of) localized dermatomal HZ should be excluded

• Any gastrointestinal or metabolic condition that could interfere with the absorption of the oral medication

• History of thrombosis/thromboembolic event, known coagulopathy

• Have hearing loss with progression over the previous 5 years, sudden hearing loss, or middle or inner ear disease such as otitis media, cholesteatoma, Meniere's disease, labyrinthitis, or other auditory condition that is considered current, fluctuating, or progressive.

• Abnormality in hematology, chemistry profiles, or ECG during screening:

  • Platelet count: <100,000/ mm3
  • Lymphocytes: <600/ mm3
  • Absolute neutrophil count: <1200/ mm3
  • Hemoglobin: <9.0 g/dL
  • ALT or AST: >3.0xULN
  • eGFR: <30 mL/min
  • ECG that demonstrates clinically relevant abnormalities that may affect participant safety

Prior/Concomitant Therapy

• Less than 3 months have elapsed since last JAK inhibitors
• Glucocorticosteroids when used systematically within 1 month prior to visit 2
• Prior treatment with other concomitant investigational agents
• Hypersensitivity or allergic reaction to compounds related to JAK inhibitors
• Treatment with medication that might interfere with blood levels or have a major impact on the clinical readout of the study drug, as per discretion of the study investigator
• Participants who have received prohibited drugs that are CYP3A inducers within a 28 day or 5 half-lives (whichever is longer) period prior to the first dose of study intervention
• Participants who have received prohibited drugs that are CYP3A4 or CYP1A2 substrates with narrow therapeutic index where small concentration changes may lead to serious adverse reactions within 1 week or 5 half-lives (whichever is longer) period prior to the first dose of study intervention
• Participant has received a live attenuated vaccine ≤ 30 days prior to study screening
• Treatment with any anti-IgE therapies (eg, omalizumab, ligelizumab) within 1 months prior to screening visit

Other Exclusions

• Pregnant or breast-feeding women
• Unwillingness or inability to use a contraception method during the time of participation in the trial
• Active alcohol and/or drug abuse
• Participant is unable to complete a participant diary or complete questionnaires, or does not meet the required level of compliance (≥ 80%) with the diary

There is not a plan to make IPD available.