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ZEPOSIA® for UC Header Image ZEPOSIA® for UC Header Image

TRUE NORTH
Study Design
for ZEPOSIA

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ZEPOSIA® for UC Header Image ZEPOSIA® for UC Header Image

TRUE NORTH
Study Design
for ZEPOSIA

ZEPOSIA was evaluated in 2 multicenter, randomized, double-blind, placebo-controlled clinical studies1

TRUE NORTH Study Design1-3
2 multicenter, randomized, double-blind, placebo-controlled clinical studies in adult patients with moderately to severely active UC 2 multicenter, randomized, double-blind, placebo-controlled clinical studies in adult patients with moderately to severely active UC

OLE endpoints were evaluated at Week 46 for all patients who entered the OLE from the TRUE NORTH parent study and for a subset of patients in clinical remission or clinical response at Week 52 and had continuous ZEPOSIA exposure.4,5d The mean exposure to ZEPOSIA in the OLE was 1.5 years.4

UC Study 1 (10-week induction): 645 patients were randomized 2:1 to either ZEPOSIA 0.92 mg given orally once daily or placebo for 10 weeks, beginning with a dosage titration. The trial included patients who had an inadequate response or were intolerant to any of the following: oral aminosalicylates, corticosteroids, immunomodulators, or a biologic. Patients were required to be on stable doses of oral aminosalicylates and/or corticosteroids.1

UC Study 2 (42-week maintenance): 457 patients who received ZEPOSIA in either UC Study 1 or in an open-label arm and achieved clinical response at Week 10 were re-randomized 1:1 and were treated with either ZEPOSIA 0.92 mg (n=230) or placebo (n=227) for 42 weeks (UC Study 2), for a total of 52 weeks of treatment.1

  • aPatients who had a clinical response while they were on placebo at the end of the induction period continued to receive double-blind placebo during the maintenance period and could enter the extension trial at Week 52 or after disease relapse.2
  • bResponders are those who achieved clinical response, defined as a reduction from baseline in the 3-component Mayo score of ≥2 and ≥35%, and a reduction from baseline in the RBS of ≥1 or an absolute RBS of 0 or 1.1
  • cTRUE NORTH OLE is an ongoing trial that enrolled participants who were nonresponders at the end of induction, experienced disease relapse during maintenance, or completed maintenance treatment in the Phase 3 TRUE NORTH study or remained at study closure and received once-daily oral ZEPOSIA 0.92 mg in the Phase 2 TOUCHSTONE OLE.4,6
  • dEndpoints include clinical remission, clinical response, endoscopic improvement, and CS-free remission.4

CS=corticosteroid; OLE=open-label extension; RBS=rectal bleeding subscore; UC=ulcerative colitis.

Select Endpoint Definitions1

Primary Endpoint1

Clinical Remission

3-component Mayo score consisting of rectal bleeding subscore (RBS)=0, stool frequency subscore (SFS) 0 or 1 (and a decrease of ≥ 1 point from baseline SFS), and endoscopy subscore 0 or 1 without friability

Key Secondary Endpoints1

Clinical Response

A reduction from baseline in the 3-component Mayo score of ≥2 points and ≥35%, and a reduction from baseline in RBS of ≥1 point or an absolute RBS of 0 or 1

Endoscopic Improvement

Mayo endoscopy subscore of 0 or 1 point without friability

Endoscopic-Histologic Mucosal Improvement

Mayo endoscopy subscore of 0 or 1 without friability and histologic improvement of colonic tissue (defined as no neutrophils in the epithelial crypts or lamina propria and no increase in eosinophils, no crypt destruction, and no erosions, ulcerations, or granulation tissue, ie, Geboes <2.0)

CS-free Clinical Remission

Clinical remission at Week 52 while off corticosteroids for ≥12 weeks

Key Inclusion Criteria1,2
  • Moderately to severely active UC (Mayo score of 6 to 12)
    • With endoscopy subscore ≥2
    • With RBS ≥1
    • With SFS ≥1
  • An inadequate response or intolerance to any of the following: oral aminosalicylates, corticosteroids, immunomodulators, or a biologic
  • Patients were required to be on stable doses of oral aminosalicylates and/or corticosteroids (prednisone daily dose up to 20 mg equivalent or budesonide extended-release tablets)
Key Exclusion Criteria1,3
  • Clinically relevant cardiovascular conditions or other relevant diseases that could impact the implementation or interpretation of the trial, or put the patient at risk
  • History of uveitis or macular edema
  • Concomitant use of biologics or immunomodulators
  • Pregnant or lactating women

Among the patients considered for the UC studies, 98.8% (2152/2178)
passed protocol-defined preexisting cardiac
disorder screening7e

eIncludes UC Study 1 from the TRUE NORTH trial and the phase 2 TOUCHSTONE trial. ZEPOSIA was not studied in patients who had1,7:

  • A myocardial infarction, unstable angina, stroke, TIA, or decompensated heart failure requiring hospitalization within the last 6 months
  • New York Heart Association Class III/IV heart failure
  • Cardiac conduction or rhythm disorders, including sick sinus syndrome, significant QT prolongation (QTcF >450 msec in males, >470 msec in females), risk factors for QT prolongation, or other conduction abnormalities or cardiac condition that in the opinion of the treating investigator could jeopardize the patient's health
  • Other preexisting stable cardiac conditions without clearance from a cardiologist
  • Severe untreated sleep apnea
  • A resting heart rate less than 55 beats per minute (bpm) at baseline

QT=an extended interval between the heart contracting and relaxing; QTcF=corrected QT interval by Fridericia; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TIA=transient ischemic attack.

UC Study 1 Baseline Characteristics1,2

Baseline Patient Characteristics1,2
Male ~60%
Age ~42 years
Time Since UC Diagnosis ~7 years
Total Mayo Score ~9
Disease Severity  
Moderate Disease
(Mayo Score 6-10)
86%
Severe Disease
(Mayo Score 11-12)
14%
Concomitant Medication Use  
Mesalamine 71%
Sulfasalazine 13%
Oral Corticosteroids 33%
Prior Medication Use  
TNFi (Previous
Failure or Intolerance)
30%
Of these patients,
47% were exposed
to vedolizumab
 

At entry to UC Study 2 (maintenance),
35% of patients were in clinical remission;
29% of patients were on CS; and 31% of patients
had an inadequate response, loss of response,
or intolerance to TNFi.1

CS=corticosteroid; RBS=rectal bleeding subscore; TNFi=tumor necrosis factor inhibitor.

Explore the Efficacy
Data for ZEPOSIA

Review the
Demonstrated
Safety Profile1

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