Cristcot Announces Positive Phase 3 Results for Novel Hydrocortisone Acetate Suppository Administered with the Sephure® Suppository Applicator for the Treatment of Ulcerative Colitis of the Rectum

Pivotal Phase 3 Data Met Pre-defined Outcomes - Achieving a  Clinical Response by Day 15 and  Clinical Remission by Day 29

On Track for NDA Submission in Q1 2025

CONCORD, Mass., Jan. 9, 2025 /PRNewswire/ -- Cristcot, a clinical-stage pharmaceutical company advancing innovative therapies for gastrointestinal diseases, today announced positive topline results from its pivotal Phase 3 cessa clinical trial evaluating its novel hydrocortisone acetate (HCA) suppository administered with the Sephure® suppository applicator in patients with ulcerative colitis (UC) of the rectum.

The cessa Phase 3 trial was constructed to evaluate the safety and efficacy of Cristcot's investigational  HCA suppository formulation designed to halt acute flares in UC. The study examined the treatment for use alone as monotherapy or with other maintenance therapies (e.g., 5-ASAs, biologics, anti-TNFs, Jak inhibitors, etc.).

Key Phase 3 Study Results: 

The cessa Phase 3 trial randomized 171 patient subjects, meeting the study protocol criteria, who were experiencing moderate to severe active UC of the rectum at the time of enrollment. The study was conducted at multiple research sites around the world and patient subjects were randomized to receive either once-daily (QD), twice-daily (BID) dosing of the 90 mg hydrocortisone acetate suppository or placebo for 28 days, followed by a 10-day taper period.

• Primary Endpoint: Clinical Remission by Day 29 (Visit 7)
  • The trial achieved its primary endpoint of clinical remission, defined as a Modified Mayo Score of 0-2, which includes rectal bleeding sub-score of 0, reduction of stool frequency from baseline with sub-scores of 0 or 1 and mucosal healing as determined by an endoscopic sub-score of 0 or 1.
  • In the once-daily (QD) treatment arm, 23.0% of patients achieved clinical remission by Day 29.
  • In the twice-daily (BID) treatment arm, 17.5% of patients achieved clinical remission by Day 29.
  • When pooling both treatment active treatment arms, 20.2% of patients receiving active treatment reached clinical remission, compared to only 2.1% in the placebo group, demonstrating a statistically significant benefit.
    
    
• Secondary Endpoints: Clinical Response by Day 15 (Visit 5)
  • Rapid clinical response for both, rectal bleeding = 0 and reduction of stool frequency = 0 or 1, was observed in both active treatment arms by Day 15.
    
    
• Safety Profile
  • The treatment was well-tolerated, with no adverse events of statistical significance reported across treatment arms.
  • Side effects observed were generally mild and consistent with those typically associated with corticosteroid use.
    
    
• Patient Compliance
  • Notably, the trial demonstrated high compliance rates across treatment arms, with 97% compliance for the once-daily regimen.

"UC patients are urgently in need of a therapeutic  option to manage intermittent and acute flares, inherent in the disease profile, as current therapies often take several months to induce clinical response and up to 52 weeks to achieve remission," said Jennifer Davagian, Founder and Chief Executive Officer, Cristcot. "During the first quarter of 2025 we will be finalizing our NDA submission as we continue to build our manufacturing and commercial capabilities to bring this potentially transformative therapy to patients in the U.S. We are also evaluating marketing partnerships that would help accelerate the commercialization of the drug to market. We look forward to providing further updates in the coming months."

"Subject to FDA approval, the ability for patients to achieve symptomatic relief in as little as two weeks and clinical remission in just four weeks will be a significant advancement for UC patients," added Dr. Monika Fischer, MD, MSc, FACG, AGAF, Chief Fellow in the Division of Gastroenterology and Hepatology, Indiana University Department of Medicine. "This novel therapy is positioned to fill a critical gap in the treatment of ulcerative colitis and possibly related conditions. A novel topical steroid therapy can allow physicians to better manage acute crisis episodes and/or transition patients from one maintenance therapy to another, while reducing the burden to both patients and payers. These results demonstrate Cristcot's potential to transform how we approach flare management and change the treatment paradigm for ulcerative colitis. Cristcot's new product is a potential new best-in-class therapy that delivers better efficacy through its unique release and absorption profile."

About the cessa Trial 
This pivotal Phase 3 trial was designed to evaluate the safety and efficacy of Cristcot's hydrocortisone acetate 90-milligram suppository in patients with ulcerative colitis of the rectum. This was a randomized, multi-center, double-blind, three arm placebo-controlled study in male and non-pregnant, non-lactating female subjects aged 18 years and older. Conducted across multiple global sites, the trial enrolled 784 patient subjects with 171 meeting the criteria of the protocol who received twice-daily dosing of the suppository for 28 days, followed by a 10-day taper period. The study's primary endpoint was clinical remission at Day 29, defined by a Modified Mayo score of 0-2 including zero bleeding, reduction of stool frequency and mucosal healing. Secondary endpoints included rapid symptom relief, with significant clinical response of a reduction in both bleeding and stool frequency observed as early as Day 15.

Baseline Characteristics:

• Male or non-pregnant, non-lactating females aged 18 years and older.
• Subjects with a confirmed diagnosis of UC with an endoscopic score 2-3 extending no further than 15 centimeters (cm) from the anal verge as assessed by endoscopic procedure performed at Visit 2.
  • Note: Subjects may have a history of more extensive UC (e.g., pancolitis), but have an endoscopic score of 2-3 only in the rectum at the time of the screening endoscopy (endoscopic score 0-1 beyond 15 cm from the anal verge is not exclusionary).
• Modified Mayo sub-score for stool frequency of 1-3.
• Modified Mayo sub-score for rectal bleeding of 0-2.
• Modified Mayo endoscopic sub-score of 2-3.
• Total Modified Mayo Score (without physician global assessment) of 4-8.

About Cristcot's HCA Suppository 
Cristcot's investigational HCA suppository formulation is a novel therapy delivered using the Sephure® suppository applicator, the small-volume suppository ensures precise placement, minimizing discomfort and leakage. This innovative delivery system may likely enhance patient compliance. Unlike traditional corticosteroid treatments, the suppository's differentiated mechanism of action allows for rapid metabolism and localized efficacy, reducing systemic exposure.

About Ulcerative Colitis
UC is a life-long, chronic gastrointestinal autoimmune disease characterized by inflammation and ulcers in the lining of the large intestine, including the rectum and sometimes, all or part of the colon. Symptoms often include rectal bleeding, profuse diarrhea, bowel urgency, tenesmus, and abdominal pain significantly impacting patients' quality of life. UC flares originate in the rectum, and untreated inflammation can progress to more extensive disease, leading to hospitalization or surgery. There is no cure for UC and breakthrough flares, even while taking maintenance medication, is a known characteristic of the disease profile. Over 55% of UC patients experience 3-5 flares annually, with many reporting debilitating effects on daily activities, work, and mental health. Despite existing treatments, patients experience intermittent flares and often change therapies as a measure to treat increased disease activity. The time of transition between one treatment to another is further complicated while waiting for the new therapy to reach full efficacy potential. Gaps remain in addressing flares quickly and effectively, highlighting the need for targeted therapies that can provide rapid symptom relief and remission.

About Cristcot 
Cristcot is a clinical-stage pharmaceutical company dedicated to advancing targeted therapies for gastrointestinal diseases. The Company's lead asset, a novel hydrocortisone acetate suppository, is positioned to become the first line therapy for  ulcerative colitis. . Cristcot's diversified pipeline includes investigational development programs for ulcerative colitis, acute pancreatitis, hemorrhoid disease and other inflammatory gastrointestinal indications with an emphasis on innovative, patient-centric solutions. The company is headquartered in Austin, Texas.

For more information, please visit www.cristcot.com and connect with us Linkedin.

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Contacts

Mark C. Ensign, COO/CSO
[email protected]

Tanner Kaufman / Shana Marino
FTI Consulting
[email protected] / [email protected]

SOURCE Cristcot