Clinical Trial: A Study To Investigate The Safety And Possible Clinical Benefit Of Multistem(r) In Patients With Moderate To Severe Ulcerative Colitis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 2 Randomized, Double-blind, Placebo-controlled, Parallel Group, Multi-center Study To Investigate The Safety And Efficacy Of Multistem (Pf-05285401) In Subjects With Moderate To Severe

Brief Summary: MultiStem(r) is a new biological product, manufactured from human stem cells obtained from adult bone marrow or other nonembryonic tissue sources. Factors expressed by MultiStem cells are believed to reduce inflammation and regulate immune system function, protect damaged or injured cells and tissue, promote formation of new blood vessels, and augment tissue repair and healing. MultiStem cell treatment resulted in significant efficacy in a mouse model of Graft versus Host Disease with almost complete reversal of gastrointestinal pathology (similar to pathology that would be expected in Ulcerative Colitis). These data, together with safety data generated in 2 other clinical trials, suggest that MultiStem has the potential to be a new treatment option for patients with ulcerative colitis. This is the first study of MultiStem in this patient population and will cautiously explore the safety/toleration and potential benefit of this new treatment in patients with moderate to severe disease.

Detailed Summary:
Sponsor: Pfizer

Current Primary Outcome:

  • Change From Baseline in Endoscopic Score (as Measured by Modified Baron Score) at Week 8 [ Time Frame: Baseline and Week 8 ]
    Modified Baron Score is an instrument designed to measure endoscopic activity of ulcerative colitis. It classifies the mucosal inflammation in 4 grades (0=normal, 1=granular mucosa with an abnormal vascular pattern, 2=friable mucosa, 3=microulceration with spontaneous bleeding, 4=gross ulceration with spontaneous bleeding).
  • Change From Baseline in Rectal Bleeding Mayo Subscore at Week 4 [ Time Frame: Baseline and Week 4 ]
    Mayo Score is an instrument designed to measure disease activity of ulcerative colitis. Mayo subscores for rectal bleeding range from 0 to 3, with higher scores indicating more severe disease.
  • Change From Baseline in Rectal Bleeding Mayo Subscore at Week 8 [ Time Frame: Baseline and Week 8 ]
    Mayo Score is an instrument designed to measure disease activity of ulcerative colitis. Mayo subscores for rectal bleeding range from 0 to 3, with higher scores indicating more severe disease.
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Week 52 ]
    An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treat

    Original Primary Outcome:

    • Incidence and severity of adverse events (at Week 4 as well as at Week 8). [ Time Frame: 8 weeks ]
    • Change from baseline of endoscopic score at Week 8 as measured by modified Baron score. [ Time Frame: 8 weeks ]
    • Change from baseline of Mayo rectal bleeding sub-score at Week 8. [ Time Frame: 8 weeks ]


    Current Secondary Outcome:

    • Change From Baseline in Rectal Bleeding Mayo Subscore at Week 12 and Week 16 [ Time Frame: Baseline, Week 12, Week 16 ]
      Mayo Score is an instrument designed to measure disease activity of ulcerative colitis. Mayo subscores for rectal bleeding range from 0 to 3, with higher scores indicating more severe disease.
    • Number of Participants With Laboratory Test Abnormalities [ Time Frame: Baseline up to Week 24 ]
      The total number of participants with laboratory test abnormalities with or without regard to baseline abnormality was assessed. Laboratory parameters included: hematology (hemoglobin, hematocrit, red blood cell [RBC] count, platelet count, white blood cell [WBC] count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, erythrocyte sedimentation rate); chemistry (blood urea nitrogen and creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein; urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, microscopy (only if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase); other (follicle-stimulating hormone, human chorionic gonadotropin, stool microbiology, creatinine kinase, direct bilirubin, indirect bilirubin, gamma-glutamyl transferase, international normalized ratio.
    • Number of Participants With Potentially Clinically Significant Vital Signs Findings [ Time Frame: Baseline up to Week 52 ]
      Vital signs assessment included pulse rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP). Criteria for vital sign values meeting potential clinical concern included: SBP <90 millimeters of mercury (mm Hg) and >=30 mm Hg increase/decrease from baseline, DBP <50 mm Hg and >=20 mm Hg increase/decrease from baseline, pulse rate <40 or >120 beats per minute (bpm),
    • Fold Change From Baseline in Fecal Calprotectin at Weeks 4, 8, 12, and 16 [ Time Frame: Baseline, Weeks 4, 8, 12 and 16 ]
      Fecal calprotectin, a very stable marker, is a 36kDa calcium and zinc binding protein which is neutrophil-derived. It represents 60% of cytosolic proteins in granulocytes and is a measurement of neutrophil migration to the gastrointestinal tract.
    • Fold Change From Baseline in C-Reactive Protein (CRP) at Weeks 4, 8, 12, and 16 [ Time Frame: Baseline, Weeks 4, 8, 12 and 16 ]
      CRP is an acute-phase protein which provides an objective criterion of inflammatory activity. CRP has a short half-life (19 hours) and therefore rises early after the onset of inflammation and rapidly decreases after resolution of the inflammation. It is induced by interleukin-6, TNF-alpha and other pro-inflammatory cytokines that are produced within the intestinal lamina propria.
    • Percentage of Participants With Rectal Bleeding Mayo Subscore of Zero at Weeks 4, 8, 12, and 16 [ Time Frame: Week 4, 8, 12 and 16 ]
      Mayo subscores for rectal bleeding range from 0 to 3 (0=no blood seen; 1=streaks of blood with stool less than half the time; 2=obvious blood with stool most of the time; 3=blood alone passes).
    • Percentage of Participants in Endoscopic Remission at Week 8 [ Time Frame: Week 8 ]
      Modified Baron Score is an instrument designed to measure endoscopic activity of ulcerative colitis. It classifies the mucosal inflammation in 4 grades (0=normal, 1=granular mucosa with an abnormal vascular pattern, 2=friable mucosa, 3=microulceration with spontaneous bleeding, 4=gross ulceration with spontaneous bleeding). Endoscopic remission is defined as modified Baron Endoscopic Score equal to 0.
    • Percentage of Participants in Clinical Remission at Week 8 [ Time Frame: Week 8 ]
      Clinical remission is defined as a total Mayo score of 2 points or lower, with no individual subscores exceeding 1 point.
    • Percentage of Participants With Decrease From Baseline of at Least 1 Point in Rectal Bleeding Mayo Subscore at Weeks 4, 8, 12, and 16 [ Time Frame: Baseline, Weeks 4, 8, 12 and 16 ]
      Mayo subscores for rectal bleeding range from 0 to 3 (0=no blood seen; 1=streaks of blood with stool less than half the time; 2=obvious blood with stool most of the time; 3=blood alone passes). A decrease from baseline score indicates improvement.
    • Percentage of Participants With Endoscopic Response at Week 8 [ Time Frame: Week 8 ]
      Endoscopic response is defined as a decrease in modified Baron endoscopic score from baseline of at least 2 points.
    • Percentage of Participants in Clinical Response at Week 8 [ Time Frame: Week 8 ]
      Clinical response is defined as a decrease in total Mayo score from baseline of at least 3 points and at least 30 percent (%), with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1.


      • Original Secondary Outcome:

      • Changes in laboratory measurements of safety and vital signs (at Week 4 as well as at Week 8). [ Time Frame: 8 weeks ]
      • Changes from baseline at Week 4 as well as at Week 8 in the following biomarker levels: fecal calprotectin, CRP. [ Time Frame: 8 weeks ]
      • Proportion of subjects with a Mayo rectal bleeding sub-score equal 0 at Week 4 as well as at Week 8. [ Time Frame: 8 weeks ]
      • Proportion of subjects in endoscopic remission at Week 8 [ Time Frame: 8 weeks ]
      • Proportions of subjects in clinical remission at Week 8 [ Time Frame: 8 weeks ]
      • Proportions of subjects with a decrease from baseline of at least one point in Mayo rectal bleeding sub-score at Week 4 as well as at Week 8. [ Time Frame: 8 weeks ]
      • Proportion of subjects with an endoscopic response at Week 8 [ Time Frame: 8 weeks ]
      • Proportion of subjects with clinical response at Week 8 [ Time Frame: 8 weeks ]
      • Change from baseline in total Mayo score at Week 8. [ Time Frame: 8 weeks ]
      • Changes from baseline in partial Mayo score at Week 2, Week 4, Week 6, as well as at Week 8. [ Time Frame: 8 weeks ]
      • Daily patient-reported rectal bleeding scores, to be modeled longitudinally. [ Time Frame: 8 weeks ]
      • Change from baseline of Mayo rectal bleeding sub-score at Week 4. [ Time Frame: 4 weeks ]
      • Changes in biopsy histology score at Week 8 (measured by Riley Index). [ Time Frame: 8 weeks ]


      Information By: Pfizer

      Dates:
      Date Received: November 10, 2010
      Date Started: February 2011
      Date Completion:
      Last Updated: January 26, 2016
      Last Verified: January 2016