Phase 3 Study to Evaluate the Safety and Efficacy of Hydrocortisone Acetate Suppositories

Hydrocortisone acetate 90 mg or placebo will be administered as a rectal suppository with a Sephure suppository applicator. Two arms of the study will receive different dosage regimens of hydrocortisone acetate, and the third arm will receive placebo. All subjects will administer the study drug twice a day; once in the morning and once in the evening for 28 days.

The study population will consist of male and non pregnant, non lactating females aged 18 years and older with a confirmed diagnosis of active ulcerative colitis of the rectum.

• Twice daily 90 mg hydrocortisone acetate suppository administered with Sephure applicator (Combination product), also known as Twice Daily - Active: Twice daily 90 mg hydrocortisone acetate suppository administered with Sephure applicator
• Once daily 90 mg hydrocortisone acetate or placebo suppository administered with Sephure applicator (Combination product), also known as Once Daily - Active: Once daily 90 mg hydrocortisone acetate or placebo suppository administered with Sephure applicator
• Twice daily placebo suppository administered with Sephure applicator (Combination product), also known as Twice Daily - Placebo: Twice daily placebo suppository administered with Sephure applicator

Primary outcomes

• Clinical Remission [29 days]: The primary efficacy endpoint was specified as the between-treatment group (HCA Suppository 90 mg bid versus placebo and HCA Suppository 90 mg qd versus placebo) difference in the proportion of subjects with clinical remission at the End of Treatment visit (Day 29). Clinical remission was defined as a Modified Mayo Total Score of 0 to 2, with stool frequency subscore of 0 or 1 (minimum 1 point decrease from baseline), rectal bleeding subscore of 0, and endoscopic subscore of 0 or 1.

Secondary outcomes

• Reduction of Stool Frequency [29 days]: Reduction of stool frequency measured using Mayo Scoring sub score of stool frequency to assess the change in stool frequency from Baseline (Day 1) to End of Treatment (Day 29) and from Baseline (Day 1) to Follow-up (Day 15).
• Rectal Bleeding [29 days]: Rectal Bleeding measured using Mayo Scoring sub-score of rectal bleeding equal to assess the change in rectal bleeding in active treatment groups vs. placebo group from Baseline (Day 1) to End of Treatment (Day 29) and from Baseline (Day 1) to Follow-up (Day 15).

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Male or non pregnant, non lactating females aged 18 years and older.
* Able to provide informed consent.
* Subjects with a confirmed diagnosis of active UC of the rectum, extending no more than 15 centimeters (cm) (5.9 inches) proximal to the anal verge as assessed by colonoscopy performed at Visit 2. Note: Subjects may have a history of more extensive UC (e.g., pancolitis), but have active disease only in the rectum at the time of enrollment.
* 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.

Exclusion Criteria:

* History or current diagnosis of bacterial or other infectious colitis, radiation enteritis and radiation proctitis, Crohn's disease, collagenous colitis and indeterminate colitis.
* Prior gastrointestinal surgery except appendectomy, cholecystectomy, and hernia.
* Concomitant active lower gastrointestinal disease (except Irritable Bowel Syndrome) or distortion of intestinal anatomy.
* Bleeding hemorrhoids at the time of enrollment.
* Acute diverticulitis at the time of enrollment.
* Acute or chronic pancreatitis at the time of enrollment.
* Unmanaged celiac disease at the time of enrollment.
* Positive stool test for enteric pathogens, Clostridium difficile, or presence of ova and parasites.
* Taking a prohibited medication.

Participant flow

Outcome results

• Clinical Remission (Primary), Count of participants, Participants: Twice Daily - Active 11 (1.3126 to 60.7941); Once Daily - Active 14 (1.5305 to 69.1744); Placebo 1 (p 0.0005)
• Reduction of Stool Frequency (Secondary), Number, participants: Twice Daily - Active 34; Once Daily - Active 38; Placebo 26 (p 0.0550)
• Rectal Bleeding (Secondary), Number, Participants: Twice Daily - Active 34; Once Daily - Active 31; Placebo 10 (p .0001)

Adverse events

Time frame: Adverse events were reported from time of screening until end of trial (Safety and Symptom Follow-up Visit), 73 days.

Other adverse events by term

89 more sites not listed.

• Study Protocol and Statistical Analysis Plan (PDF, 2023-09-08)

• Jennifer Davagian, Study director, Cristcot LLC

NIH grants: 2019