Inclusion Criteria:

• Participants are male or female ≥ 18 years up to ≤ 75 years of age.
• Capable of giving signed informed consent and able to comply with the requirements and restrictions listed in the ICF and in the study protocol, including compliance with the SoA.
• Previously had an index (first) episode of pericarditis which, in the judgement of the Investigator based on the available data, met the criteria for an acute pericarditis event, using the 2015 ESC Guidelines for the Diagnosis and Management of Pericardial Diseases as a frame of reference, i.e., met at least 2 of the 4 following criteria:
  • Pericarditic chest pain
  • Pericardial rub
  • New widespread ST-segment elevation or PR-segment depression on ECG
  • Pericardial effusion (new or worsening)

Additional supportive findings could include elevations of markers of inflammation (i.e., CRP, ESR or WBC count) or evidence of pericardial inflammation by an imaging technique (e.g., MRI).

• In the judgement of the Investigator, based upon the available diagnostic information, has an ongoing symptomatic episode of pericarditis, or may have an episode of recurrent pericarditis in the next 4 weeks. Participants with an active episode of pericarditis at the screening visit must have Day 1 visit and initiate study treatment as soon as possible (within a maximum of 7 days).
• CRP assessment by local laboratory assessment prior to first dose of study treatment on Day 1, either:
  • CRP > 1 mg/dL,
  • CRP ≤ 1 mg/dL (approximately 10 participants)

Participants with CRP ≤ 1 mg/dL must be receiving concurrent corticosteroid treatment for RP and have evidence of pericardial inflammation by MRI, either at the screening asses.

• Pericarditis pain score ≥ 4 based on the 11-point NRS on Day 1.
• If participants require treatment with NSAIDs, colchicine, and/or oral corticosteroids (in any combination) based on Investigator judgement, doses of each are required to be stable:
  • NSAIDs and/or colchicine: stable for at least 3 days prior to study treatment
  • Oral corticosteroids: stable for at least 7 days prior to study treatment
  • It must be anticipated that the participant will continue NSAIDs, colchicine, and/or oral corticosteroids at the same dose levels for the duration of the 6-week Open-Label Treatment Period.
• Agrees to refrain from making any new, major life-style changes that may affect pericarditis symptoms (e.g., starting a new diet or change in exercise pattern) from the time of signature of the ICF to the last on-treatment visit.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions (either a or b) applies:
  • Is not a FOCBP
  • Is a FOCBP and using a highly effective contraceptive method with a failure rate of < 1% per year, as described in Appendix 1, during the study treatment period and for at least 30 days after the last dose of study treatment. The Investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study treatment. Methods considered highly effective birth control methods are listed in Appendix 1.
  • A FOCBP must have a negative serum pregnancy test at screening
  • A FOCBP must refrain from donating oocytes for at least 90 days after the last dose of study treatment.
• A male participant is eligible to participate if they agree to the following during the study treatment period and for at least 90 days after the last dose of study treatment:
  • Refrain from donating sperm
  • Agree to use a male condom with a FOCBP. Female partners of male participants should consider using an additional highly effective contraceptive method with a failure rate of < 1% per year

Exclusion Criteria:

• 1. Has a current or prior diagnosis of pericarditis that is secondary to specific prohibited etiologies, including TB; neoplastic, purulent, or radiation etiologies; post-thoracic blunt trauma (e.g., motor vehicle accident); myocarditis; or systemic autoimmune diseases with exception of Still’s disease.
• History of clinically significant immunosuppressive disorder, autoimmune/autoinflammatory disorder, primary or secondary immunodeficiency, or disorder with clinically significant effect on CRP.
• Has received treatment within 6 months prior to the first dose of study treatment with any systemic immunosuppressants (other than, for example, corticosteroids or mycophenolate) which, in the opinion of the Investigator (in consultation with the Medical Monitor), may interfere with the study endpoints.
• Has received treatment within 12 weeks prior to first dose of study treatment with any biologic immunomodulatory therapy (such as IL-targeted therapy or TNF-targeted therapy), JAK-targeted therapy, or other targeted immunomodulatory therapy.
• Previously received IL-1-directed treatments, for example, rilonacept or anakinra.
• Previously received any biologic or targeted therapy for pericarditis (not including NSAIDs, colchicine or corticosteroid treatment), including investigational therapies given in a clinical trial.
• Has received treatment within 4 weeks prior to first dose of study treatment with any injected glucocorticoids (including IV, subcutaneous, intramuscular and intrathecal injections, but not including intraarticular injections).
• Has a history of myeloproliferative disorder, demyelinating disease, or symptoms suggestive of multiple sclerosis.
• Receipt of any live vaccine(s) within 28 days prior to the first dose or SARS CoV-2 vaccination within 14 days prior to the first dose of study treatment (Day 1). Approved nonlive vaccines, including SARS-CoV-2, can be administered according to local vaccination standards.
• Has a history of malignancy of any organ system within the past 5 years (other than localized carcinoma in situ of the cervix; or fully excised non‑melanoma skin cancers or non-metastatic prostate cancer that has been stable for ≥ 6 months).
• Has a known or suspected currently active clinically significant infection or a history of chronic or recurrent infectious disease, including, but not limited to, chronic renal infection, chronic chest infection, sinusitis, recurrent urinary tract infection, or an open, draining infected skin wound. Localized skin infection and localized cutaneous tinea are not exclusionary.
• Has been treated with oral antibiotics within 2 weeks; or has had a serious infection, has been hospitalized for an infection, or has been treated with IV antibiotics for an infection within 2 months of screening.
• Has had an organ transplant.
• A history of any of the following:
  • Drug/chemical abuse within 2 years prior to screening
  • Alcohol abuse
  • Alcohol intake of ≥ 14 alcohol equivalents per week in the 6 months prior to screening or ≥ 7 alcohol equivalents per week in the month prior to screening.
• Significant other cardiovascular disease that would affect the interpretation of study data or the safety of the participant’s participation in the study, per the judgment of the Investigator, including myocardial infarction or unstable angina, heart failure with New York Heart Association Class III or IV symptoms, arterial or venous thrombosis, or stroke within 12 months prior to screening.
• Any of the following renal conditions:
  • Clinical history of kidney stones within 12 weeks prior to screening
  • History of recurrent kidney stones, defined as ≥ 2 instances of symptomatic kidney stones within 5 years prior to screening
  • Acute kidney injury within 12 weeks prior to screening
  • Signs or symptoms of volume depletion or dehydration at screening or Day 1 per Investigator judgement
• Current or prior diagnosis of fatty liver disease, including metabolic dysfunctionassociated steatotic liver disease (formerly known as non-alcoholic fatty liver disease) or alcohol-related fatty liver disease.
• Previously received any compound selectively targeting NLRP3, including investigational therapies given in a clinical trial.
• Tests performed at a central laboratory at screening that meet any of the following criteria (out of range labs may be rechecked one time, after consultation with the Medical Monitor, before the participant is considered a screen failure):
  • WBC count < 3.0 × 103 cells/mm3
  • ANC < 1.5 × 103 cells/mm3 c. Lymphocyte count < 0.5 × 103 cells/mm3
  • Platelet count < 100 × 103 cells/mm3
  • Hemoglobin < 9 g/dL f. AST or ALT ≥ 2.0 × ULN
  • Total bilirubin level > 1.5 × ULN unless the participant has been diagnosed with Gilberts’ disease and this is clearly documented
  • eGFR < 60 mL/min/1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration equation at screening
  • Presence of HBsAg or positive for total HBcAb, or positive HCV at screening. Successfully treated HCV patients (undetectable HCV RNA) are eligible for enrollment. Participants who are immune due to HBV natural infection or HBV vaccination are eligible.
  • Positive or more than 1 indeterminate QuantiFERON®-TB test at screening. A participant whose first screening QuantiFERON-TB test result is indeterminate may have the test repeated once during screening with the result available before Day 1. If the second QuantiFERON-TB test result is also indeterminate, the participant will not be enrolled in the study and should be considered screen failed. Participants who had latent TB and received prophylaxis may be eligible upon consultation with the Medical Monitor.
  • HIV infection, defined as confirmed positive HIV antigen/antibody at screening.
  • Positive for drugs in the urine drug screen without documented medical explanation.
• Participants with a confirmed event of QTcF interval prolongation of > 450 msec in males and > 470 msec in females at screening or Day 1.
• Uncontrolled arterial hypertension characterized by a systolic BP > 160 mm Hg or diastolic BP > 100 mm Hg. One retest may be allowed on a different day during the Screening Period, to allow treatment change or compliance to take effect. Note: Determined by 2 consecutive elevated readings. If an initial BP reading exceeds this limit, the BP may be repeated once after the participant has rested sitting for ≥ 10 minutes. If the repeat value is less than the criterion limits, the second value may be accepted.
• Any other clinically significant laboratory abnormality that might affect the interpretation of study data or safety of the participant’s participation in the study, per judgment of the Investigator.
• Hypersensitivity to any of the VTX2735 excipients.
• Positive pregnancy test or lactating female participant.
• Clinically important history of a medical disorder that would compromise safety or data quality, per the Investigator's judgment.
• Received another investigational drug within 30 days before screening or is planning to receive an investigational drug (other than that administered during this trial) or use an investigational device at any time during the trial.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 12/12/2024. Questions regarding updates should be directed to the study team contact.