Safety, Tolerability, Efficacy Study of PUR 0110 Rectal Enema in Mild-to-Moderate Distal Ulcerative Colitis
Condition: Left-Sided Ulcerative Colitis; Proctosigmoiditis
MeSH terms: Colitis; Colitis, Ulcerative; Proctocolitis; Ulcer
Study type: Interventional
Phase: Phase 2

Summary: 
      PUR 0110 is a 100% natural novel investigational medicinal product that has been demonstrated
      in several in vitro and in vivo pharmacology studies to have potent anti-inflammatory,
      anti-oxidative and immunomodulatory effects. This exploratory Phase 2a study is a
      first-in-patient study to evaluate the safety, tolerability, biomarker effect and efficacy of
      PUR 0110 rectal enema in patients with active mild-to-moderate distal ulcerative colitis
      (UC).

      The study is a multicenter, randomized, double-blind, parallel-group, dose-ranging,
      placebo-controlled study. To be eligible for inclusion into the study, patients must either
      be newly diagnosed or have on-going active mild-to-moderate distal ulcerative colitis of at
      least 3 months duration confirmed in either case by flexible sigmoidoscopy and biopsy at the
      Screening Visit. In addition, patients must have a modified Mayo score of ≥5 to ≤10 including
      a sigmoidoscopy inflammation grade and rectal bleeding scores of ≥2 each. Eligible patients
      will be randomly assigned to receive either PUR 0110 250 mg, 500 mg or 1000 mg or placebo
      rectal enema in a 1:1:1:1 ratio. Patients will self-administer the assigned study medication
      intrarectally once-daily at bedtime (10:00 p.m +/- 1 hour) for 2 weeks.

      Patients will be evaluated for safety by adverse events, clinical laboratory tests, vital
      signs, physical examination, electrocardiogram (ECG), and concomitant medications. Efficacy
      evaluations will include the modified Mayo score, patient-defined response and remission,
      Investigator Assessment of Ulcerative Colitis Symptom Score, Inflammatory Bowel Disease
      Questionnaire (IBDQ), and biomarkers of inflammation, apoptosis and total cell death, lipid
      peroxidation and in vivo oxidative stress, and antioxidant defense mechanisms in plasma,
      serum, urine, feces and biopsy tissue. Patients will have a flexible sigmoidoscopy and biopsy
      12 hours after the last dose of study medication.
    

Detailed description: 
      Safety/Primary Outcome Parameters:

        -  Incidence, nature and severity of adverse events

        -  Incidence, nature and severity of clinical laboratory test abnormalities

      Efficacy/Secondary Outcome Parameters:

        -  Clinical remission defined as an endoscopy score of ≤ 1, a rectal bleeding score of 0,
           and an improvement or no change from baseline in the stool frequency score at the end of
           2 weeks of treatment / withdrawal visit;

        -  Clinical response rate defined as the percentage of patients with a drop of ≥3 points
           from the baseline overall modified Mayo score;

        -  Patient defined response and remission rates;

        -  Change from baseline in the overall modified Mayo score (Disease Activity Index);

        -  Change from baseline in each of the 4 individual sub-scores of the modified Mayo score;

        -  Change from baseline in Investigator Assessment of UC Symptom Score (total and
           individual symptom scores)

        -  Change from baseline in IBDQ score (total and the 4 individual dimension scores)

        -  Proportion of patients with treatment failure;

        -  Change from baseline in serum lutein levels;

        -  Change from baseline in C-reactive protein (CRP), high sensitivity CRP (hs-CRP),
           erythrocyte sedimentation rate (ESR), fecal calprotectin (FCP), and fecal lactoferrin
           (FL).

        -  Change from baseline in exploratory biomarkers including: serum interleukin-2 (IL-2),
           IL-6, IL-8, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-α),
           transforming growth factor-beta (TGF-beta), IL-4, IL-10, IL-17, IL-23, human
           beta-Defensin-2 (hBD-2), malondialdehyde (MDA), lipoxin A4 (LXA4), glutathione (GSH),
           M30 and M65 apoptosomes in serum and biopsies, and plasma and urinary isoprostane
           levels.
    

Intervention name(s): PUR 0110 Rectal Enema 250 mg; PUR 0110 Rectal Enema 500 mg; PUR 0110 Rectal Enema 1000 mg; Placebo Enema
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): PUR 0110 Rectal Enema 250 mg, once-daily, intrarectally; PUR 0110 Rectal Enema 500 mg, once-daily, intrarectally; PUR 0110 Rectal Enema 1000 mg, once-daily, intrarectally; Placebo Enema, once-daily, intrarectally
Other intervention name(s): Active treatment arm; Active treatment arm; Active treatment arm; Placebo arm
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: PUR 0110; PUR 0110 Rectal Enema; Distal Ulcerative Colitis; Left-Sided Ulcerative Colitis; Mild; Moderate