Ensayos clínicos

Inclusion Criteria:

• Male or female participants between the ages of 18 (or the minimum country-specific age of consent if ≥ 18) and 75 years, inclusive, at Visit 1 (Screening).
• Participants with a diagnosis (or recognizable symptoms consistent with a diagnosis) of moderate to severe HS for at least one year (365 days) prior to Visit 1 (screening).
• HS lesions (Hurley Stage II-III) present in at least two distinct anatomic areas (e.g., left and right axilla; or left axilla and left inguino-crural fold).
• Inadequate response to at least a 4-week (28 day) treatment with an oral antibiotic for the treatment of HS, or for whom oral antibiotic treatments are otherwise medically inadvisable (eg, because of important side effects or safety risks). 
  • Note: Enrollment of participants on a background of concomitant oral antibiotic therapy for treatment of HS will be limited to ≤ 20% of total participant population. The dosing regimen (dose and frequency) of concomitant oral antibiotic therapy must have been stable for at least 8 weeks (56 days) prior to the baseline (Day 1) visit and must remain stable throughout study participation.
• Anti-TNF naïve; or Has initiated only one anti-TNF treatment including participants with inadequate response to the anti-TNF; Note: participants who initiated more than one anti-TNF treatments are not eligible. Enrollment of participants with inadequate response to one anti-TNF will be limited to ≤ 30% of total participant population. Inadequate response to one TNF-inhibiting biologic agent administered in accordance with its labeling recommendations. The TNF-inhibiting biologic could have been discontinued due to its being deemed inadequately effective and/or not tolerated as defined, for the purpose of this study, by the Investigator’s and participant’s opinions that the participant did not experience adequate benefit from the anti-TNF plus the presence of sufficient residual disease activity to meet the entry criteria. The anti-TNF biologic could also have been discontinued due to lack of continued access. The anti-TNF s should have been discontinued for a minimum of the washout period defined as follows (biosimilars of the below agents should be considered the same as the originators):
  • adalimumab (Humira®): 6 weeks;
  • infliximab (Remicade®), golimumab (Simponi®): 10 weeks;
  • certolizumab pegol (Cimzia®): 12 weeks.
• Participant must agree to daily use (and through follow-up) to one of the non-prescription topical antiseptics on their HS lesions such as: chlorhexidine gluconate, benzoyl peroxide, pyrithione zinc, or dilute bleach in bathwater.
• Total AN of ≥ 4 at baseline; and a draining fistula count of ≤ 20 at baseline.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Body Mass Index (BMI) ≥ 17.5 kg/m^2 and body weight ≥ 40 kg.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol.

Exclusion Criteria:

• Evidence of other active skin disease or condition (e.g., bacterial, fungal, or viral infection) at the time of screening or baseline visit that would interfere with the evaluation of HS.
• Any psychiatric condition including recent (within the past year) or active suicidal ideation or behavior that meets any of the following criteria at screening: 
  • Suicidal ideation associated with actual intent and a method or plan in the past year: “Yes” answers on items 4 or 5 of the Columbia suicide severity rating scale (C-SSRS);
  • Previous history of suicidal behaviors in the past 5 years: “Yes” answer (for events that occurred in the past 5 years) to any of the suicidal behavior items of the C-SSRS;
  • In the opinion of the investigator or Sponsor (or designee) exclusion is required.
• Have any condition possibly affecting oral drug absorption; e.g., gastrectomy, clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric bypass. Procedures such as gastric banding, that simply divide the stomach into separate chambers, are NOT exclusionary.
• Have current or recent (within the past year) history of severe, progressive, or uncontrolled renal, hepatic, hematological, GI, metabolic, endocrine, pulmonary, cardiovascular, or neurological disease.
• Have acute coronary syndrome (eg, myocardial infarction, unstable angina pectoris) or any history of significant cerebrovascular disease within 24 weeks of screening.
• History of any lymphoproliferative disorder (such as Epstein-Barr virus [EBV] – related lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease.
• History of recurrent (≥ 2) venous thrombosis or any arterial thromboembolism or known blood clotting disorders.
• History (single episode) of multidermatomal herpes zoster or disseminated herpes simplex, or a recurrent (more than one episode of) localized, 1-2 dermatomal herpes zoster.
• History of infection (not including infection symptoms resulting from HS) requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator within 3 months (90 days) prior to first dose of IP or a history of infection requiring oral antimicrobial therapy within 2 weeks prior to the first dose of IP.
• Infected with Mycobacterium tuberculosis (TB).
• Have known immunodeficiency disorder or a first-degree relative with a hereditary immunodeficiency.
• Have any malignancies or history of malignancies with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
• Have undergone significant trauma or major surgery within 1 month (30 days) prior to screening or plan to undergo surgery during the treatment period.
• Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or IP administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
• Participant requires, or is expected to require, opioid analgesics for any reason.
• Participant received prescription topical therapies for the treatment of HS within 14 days prior to the baseline (Day 1) visit.
• Receipt of systemic therapies for HS including non-biologics with potential therapeutic impact for HS less than 28 days or within 5 half-lives (if known), whichever is longer, prior to the baseline (Day 1) visit (other than permitted antibiotics).
• Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of IP used in this study (whichever is longer).
• Screening 12-lead ECG that demonstrates clinically significant abnormalities requiring treatment (e.g., acute myocardial infarction, serious tachy- or brady-arrhythmias) or that are indicative of serious underlying heart disease (eg, cardiomyopathy, major congenital heart disease, low voltage in all leads, Wolff-Parkinson-White syndrome) and other clinically relevant abnormalities which may affect participant safety or interpretation of study results. Specifically, participants with screening Fredericia corrected QT interval (QTcF) > 450 milliseconds (msec) should be excluded. If QTcF exceeds 450 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF should be used to determine the participant’s eligibility. 20. A history of additional risk factors for torsade de pointes (TdP) (e.g., heart failure [New York Heart Association status of Class III or IV], hypokalemia, family history of Long QT Syndrome).
• Infected with human immunodeficiency virus (HIV), hepatitis B or hepatitis C viruses:
  • Participants who are hepatitis C virus (HCV) antibody (Ab) positive require further testing with HCV ribonucleic acid (RNA) polymerase chain reaction (PCR) and are allowed to enroll if HCV RNA PCR is negative;
  • Participants who are hepatitis B surface antigen (HBsAg) positive are not eligible for the study;
  • Participants who are HBsAg negative and hepatitis B core antibody (HBcAb) positive should be reflex tested for hepatitis B surface antibody (HBsAb) and if HBsAb is positive, may be enrolled in the study; if HBsAb is negative, the participant is :not eligible for the study.
• Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat, if deemed necessary:
  • Hemoglobin < 9.0 g/dL or hematocrit < 30% (< 0.30 v/v);
  • Absolute lymphocyte count (ALC) < 1.0 x 109 /L (< 1000/mm^3);
  • Absolute neutrophil count (ANC) < 1.5 x 10^9 /L (< 1500/mm^3);
  • Platelet count < 100 x 10^9 /L (< 100,000/mm^3 );
  • < eGFR < 60 mL/min/1.73 m^2 using SCr or cystatin C based calculation;
  • ≥ AST or ALT ≥ 1.5 times the upper limit of normal (ULN);
  • ≥ Total bilirubin ≥ 1.5 time the ULN (for participants with a history of Gilbert’s syndrome: direct bilirubin ULN);
  • Creatinine kinase (CK) > 3 times the ULN and positive urine myoglobin;
  • Positive urine drug screen;
  • In the opinion of the investigator or sponsor, any uncontrolled clinically significant laboratory abnormality that would affect interpretation of study data or the participant’s participation in the study.
• History of alcohol or substance abuse, unless in full remission for greater than 6 months prior to Day 1.
• Donation of blood in excess of 500 mL within 8 weeks prior to Day 1.
• In the opinion of the investigator or sponsor, the participant is inappropriate for study entry.
• Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study.