Testing Zasocitinib (Dose A) against a placebo for hidradenitis suppurativa

Exclusion

• −Allergies and Adverse Drug Reactions Exclusions:
• −Participant has a history of significant drug allergy (such as anaphylaxis).
• −Participant has a known or suspected allergy to zasocitinib or any of its components.
• −Participant has presence of hepatitis C virus (HCV) antibody and a positive confirmatory test result for HCV RNA (nucleic acid test or polymerase chain reaction \[PCR\]). In the EU/EEA, if the participant has total anti-HCV antibody positivity at screeningScreeningThe checks done before joining, to see whether a study fits.Read more → but is confirmed to have no detectable HCV RNA by PCR testing, HCV RNA PCR testing will be assessed every 3 months until end of trial (EOT).
• −Participant has presence of positive hepatitis B virus surface antigen (HBsAg), or indeterminate HBsAg, presence of HBV DNA (regardless of serology), or positive anti-hepatitis B core antibody (HBcAb) without concurrent positive HBsAb (HBcAb+ and HBsAb-). In the EU/EEA, if the participant has total anti-HBc antibody positivity at screening but is confirmed to have no detectable HBV DNA by PCR testing, the participant will repeat HBV DNA PCR testing every 3 months until the EOT; if a participant has anti-HBsAb positivity at screening but is confirmed to have no detectable HBV DNA by PCR testing, unless the participant has documented completion of the HBV vaccination series by medical history, the participant will repeat HBV DNA PCR testing every 3 months until the EOT. Note: For other countries in which there are hepatitis B screening guidelines, these can be done per local regulations or country standard of careStandard of careThe treatment normally given for a condition outside a study.Read more →.
• −Participant has positive results for HIV by serology, regardless of viral load.
• −Target Disease-Related Exclusions:
• −Participant has a draining tunnel count of greater than (\>) 20 at screening or Day 1.
• −Participant has any other active skin disease or condition (for example, bacterial cellulitis, Candida intertrigo, extensive condyloma) that may, in the opinion of the investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →, interfere with the assessment of HS or participant has developed a concomitant comorbid skin condition that, in the opinion of the investigator, would interfere with the trial assessments.
• −Participant has a diagnosis of sarcoidosis, systemic lupus erythematosus, or active inflammatory bowel disease.
• −Participant has a diagnosis of inflammatory conditions other than HS, including but not limited to, psoriasis, psoriatic arthritis, and rheumatoid arthritis.
• −Recent/Concurrent Infectious Disease Exclusions:
• −Tuberculosis (TB):
• −Participants have a history of active TB infection, regardless of treatment status.
• −Participants have signs or symptoms of active TB (including, but not limited to, chronic fever, chronic productive cough, night sweats, or weight loss) as judged by the investigator.
• −Participants have evidence of latent tuberculosis infection (LTBI) as evidenced by a positive QuantiFERON (QFT) result OR 2 indeterminate QFT results, and participant does not have documentation of appropriate LTBI prophylaxis or is not able or not willing to initiate appropriate LTBI prophylaxis. Participant remains eligible if there are no signs/symptoms of active TB AND documentation of no history of active TB can be provided AND (1) participant can provide documentation of prior and complete treatment for LTBI (appropriate in duration and type per current local country guidelines) or (2) participant has a positive QFT result or 2 indeterminate QFT results but has initiated prophylaxis (appropriate in duration and type per current local guidelines) a minimum of 2 weeks prior to Day 1. In the EU/EEA, participants with evidence of LTBI, regardless of prophylaxis treatment status, must receive approval to participate in the trial from an infectious disease or other TB specialist (for example, pulmonologist).
• −Note: TB prophylaxis regimens should be administered according to local guidelines; however, because of potential interactions with zasocitinib, rifampin should not be used. For isoniazid monotherapy, a minimum of 6 months should be used. TB testing should be conducted using QFT-TB Gold submitted to the central laboratory unless alternate or additional tests are required per local guidelines.
• −Participant has had any imaging trial during or 6 months prior to screening, including x-ray, chest computed tomography, magnetic resonance imaging, or other chest imaging suggesting evidence of current active or a history of active TB. X-ray is required for all participants regardless of QFT-TB Gold results unless the participant has had normal chest imaging in the 6 months prior to screening.
• −Herpes infections:
• −Participant has active herpes virus infection, including herpes zoster or herpes simplex 1 and 2 (demonstrated on physical examination and/or medical history) at screening or Day 1.
• −Participant has history of serious herpetic infection that includes any episode of disseminated disease, multidermatomal herpes zoster, herpes encephalitis, ophthalmic herpes, or recurrent herpes zoster (defined as 2 episodes within 2 years).
• −Nonherpetic viral diseases:
• −Other infectious diseases:
• −Participant has a history of active infection or febrile illness within 10 days prior to Day 1, as assessed by the investigator.
• −Participant has a history of symptoms suggestive of systemic or invasive infection within 30 days prior to Day 1.
• −Participant has a history of bacterial, viral, or fungal infection that required hospitalization or treatment with intravenous (IV) antimicrobial therapy within 8 weeks prior to Day 1, or oral antimicrobial therapy within 30 days prior to Day 1.
• −Participant has a history of chronic or recurrent bacterial disease, including but not limited to chronic pyelonephritis or cystitis, chronic bronchitis/pneumonitis, osteomyelitis, or chronic skin ulcerations (except those part of the HS clinical findings)/infections or fungal infections (except ungual onychomycosis).
• −Participant has a history of an infected joint prosthesis unless that prosthesis has been removed or replaced at least 60 days prior to Day 1.
• −Participant has a history of opportunistic infections (for example, Pneumocystis jirovecii pneumonia, histoplasmosis, or coccidiomycosis).
• −Participant had a bacterial infection within 60 days prior to Day 1 for which he or she did not receive treatment.
• −Noninfectious Disorders Exclusions:
• −Participant has any clinically significant medical condition, evidence of an unstable clinical condition (for example, cardiovascular, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, neurologic, nutritional, ophthalmologic, or immunologic), or vital signs/physical/laboratory/electrocardiogram (ECG) abnormality that would, in the opinion of the investigator, put the participant at undue risk or interfere with interpretation of trial results. These include but are not limited to:
• −Participant has a history of known or suspected condition/illness that is consistent with compromised immunity, including but not limited to any identified congenital or acquired immunodeficiency, splenectomy.
• −Participant has a history of new or unstable autoimmune disease (including but not limited to autoimmune thyroid disease, alopecia areata, lupus, Sjogren's, myasthenia gravis, or rheumatoid arthritis).
• −Participant has unstable, poorly controlled, or severe hypertension at screening, confirmed by 2 repeat assessments.
• −Participant has a history of Class III or IV congestive heart failure as defined by New York Heart Association criteria.
• −Participant has a history of lymphoproliferative disease.
• −For participants with asthma, chronic obstructive pulmonary disease, or other pulmonary illnesses, participant has been hospitalized in the past 3 months, has ever required intubation for treatment, currently requires oral corticosteroids, or has required more than 1 course of oral corticosteroids within 6 months prior to Day 1.
• −Participant has any of the following cardiovascular disease history:
• −A new diagnosis of atrial fibrillation or an episode of atrial fibrillation with rapid ventricular response or other dysrhythmia, nonacute cardiac hospitalization (for example, pacemaker implantation), pulmonary embolism, or deep venous thrombosis within the past 6 months prior to screening.
• −Participant has significant/uncontrolled psychiatric illness, in the opinion of the investigator.
• −Participant has any lifetime history of suicide attempts, or active suicidal ideation or suicidal behavior in the past 5 years, or any diagnosis of severe depression or other unstable psychiatric condition in the last 6 months, based on: (1) medical history; or (2) Columbia-Suicide Severity Rating Scale (C-SSRS) documentation by answering "yes" to Question 4 or 5 for suicidal ideation concerning the previous 5 years before participation on the C-SSRS at screening or Day 1; or (3) is clinically deemed to have a suicide risk by the investigator, or in the opinion of the investigator, would pose an unacceptable risk to the participant's safety or impact their ability to comply with trial procedures.
• −Participant has a score of 15 or above at screening or Day 1 on the 8-item Patient Health Questionnaire-8 (PHQ-8).
• −Participant has a history of active substance abuse or a history of substance abuse within 12 months prior to screening.
• −Laboratory/Physical Exclusions:
• −Participant has ECG abnormalities that are considered clinically significant and would pose an unacceptable risk to the participant if they participated in the trial, in the opinion of the investigator.
• −Participant has inadequate renal, hepatic, or pancreatic function before enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more → based on the following parameters:
• −Total bilirubin (unconjugated and/or conjugated) \>1.5 × upper limit of the normal range (ULN) unless the participant has known Gilbert's syndrome that can explain the elevation of bilirubin, or
• −Serum alanine aminotransferase (ALT) or AST \>3 × ULN, or
• −Creatinine \>1.5 × ULN. Note: The participant may be retested (1 time) to meet eligibility criteriaEligibility criteriaThe full list of requirements for taking part in a study.Read more → at the discretion of the investigator.
• −Estimated creatinine clearance lesser than (\<)45 milliliter per minute (mL/min) based on the Cockcroft-Gault calculation.
• −A history of chronic pancreatitis or recent acute pancreatitis (\<60 days/not fully resolved).
• −Participant has any of the following laboratory values at the screening visit:
• −Hemoglobin \<9.0 gram per deciliter (g/dL) (\<90.0 gram per liter \[g/L\]).
• −Absolute white blood cell count \<3.0 × 10\^9/L (\<3000/ cubic millimeters \[mm\^3\]).
• −Absolute neutrophil count (ANC) of \<1.0 × 10\^9/L (\<1000/mm\^3).
• −Absolute lymphocyte count of \<0.5 × 10\^9/L (\<500/mm\^3).
• −Platelet count \<100 × 10\^9/L (\<100,000/mm\^3).
• −Thyroid-stimulating hormone (TSH) (\>10 milli-international units per liter \[mIU/L\]) or free T4 or T3 outside the normal reference range. Note: Participants would be allowed to rescreen after treatment.
• −Triglyceride level \>=750 milligram per deciliter \[mg/dL\] (\>=8.5 millimole per liter \[mmol/L\]).
• −Creatine phosphokinase (CPK) \> ULN. CPK may be repeated once; if repeat value is Common Terminology Criteria for Adverse EventsAdverse eventAny medical problem that happens during a study, whether or not the treatment caused it.Read more → (National Cancer Institute) (CTCAE) Grade 1 or lower (or lesser than or equal to \[\<=\]2.5 × ULN) and no higher than the initial value, participant remains eligible. Investigators should assess the participant for modulating factors including concomitant medications or vigorous exercise that may affect CPK levels.
• −Participant has any other significant laboratory abnormalities that, in the opinion of the investigator, might place the participant at unacceptable risk for participation in this trial.
• −Participant does not tolerate venipuncture or inability to be venipunctured.
• −Other Exclusions:
• −Participant has a history of substance abuse within 12 months prior to Day 1.
• −Participants who have given greater than 500 mL of blood or plasma within 30 days prior to screening (during a clinical trialInterventional studyA study where participants are given something to see what happens.Read more → or at a blood bank donation) or plan to donate blood during the course of the trial.
• −Participant is compulsorily detained for treatment of either a psychiatric or physical (for example, infectious disease) illness, or is committed to an institution (for example, prison) by virtue of an order issued either by judicial or administrative authorities.
• −Participant is a trial siteTrial siteA hospital or clinic where a study is actually run.Read more → employee, an immediate family member (for example, spouse, parent, child, sibling), or is in a dependent relationship with trial site employee who is involved in the conduct of this trial or may consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more → under duress.
• −In Germany, participant is incapable of giving consent or otherwise meets criteria in Sections 136 or 137 of the Verordnung zum Schutz vor der schädlichen Wirkung ionisierender Strahlung Strahlenschutzverordnung.
• −Participants with a history of malignancy within the past 5 years prior to the screening visit are excluded, EXCEPT if the malignancy was a cutaneous squamous or basal cell carcinoma, or in situ cervical cancer that has been successfully treated and is considered cured; in the EU/EEA, investigators must document a favorable benefit-risk assessment.
• −Further exclusion criteriaExclusion criteriaThe things that would prevent someone from taking part.Read more → apply.
• −Participant has a positive pregnancy test result or plans to become pregnant during the trial period, including plans to donate ova (eggs) or sperm, or participant is pregnant or lactating/nursing.
• −Participant had a major surgery within 60 days prior to Day 1 or has a major surgery planned during the trial.
• −Any history of cerebrovascular event, myocardial infarction, coronary stenting, or aortocoronary bypass surgery. If, however, the investigator documents there are no suitable treatment alternatives available for the participant and it has been at least 6 months since the occurrence of any such event, the participant may enroll; in the EU/EEA, investigators must document a favorable benefit-risk assessment.
• −History or current status of substance use disorder and or tobacco use disorder. For participants with excessive alcohol intake or currently smoking or using chewing tobacco or with a history of long-term smoking (\>=20 pack years) or chewing tobacco use, the investigator must document a favorable benefit-risk assessment to justify the participant's inclusionInclusion criteriaThe things you must have or be for a study to consider you.Read more → in the trial.