Study of safety and effectiveness of human-derived stem cells (multistem, also known as PF-05285401) in the treatment of ulcerative colitis

• Register: EUCTR
• Last refreshed on: 6 January 2015
• Main ID: EUCTR2010-022766-27-HU
• Date of registration: 05/12/2011
• Prospective Registration: Yes
• Primary sponsor: Pfizer Limited, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK
• Public title: Study of safety and effectiveness of human-derived stem cells (multistem, also known as PF-05285401) in the treatment of ulcerative colitis
• Scientific 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 ULCERATIVE COLITIS
• Date of first enrolment: 07/02/2012
• Target sample size: 128
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022766-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Belgium, Canada, Germany, Hungary, Italy, Poland, Slovakia, Sweden, United States

Contacts

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

Inclusion criteria:
Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study. The selection of patients is based on the data available from Screening. Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1.Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, lifestyle guidelines and other study procedures.
3. Subject must be at least 18 years of age.
4. Males and females with a documented diagnosis (endoscopic or radiographic) of UC =6 months prior to screening.
5. For Cohort 1 and 2 only: Active moderate-to-severe UC defined as Mayo score of =6 and <11.
6. For Cohort 3 only: Active moderate-to-severe UC defined as Mayo score of =6.
7. Modified Baron endoscopic score of =2 determined within 21 days of first dosing for Cohort 1 and within 7 days of first dosing for Cohorts 2 and 3 (flexible sigmoidoscopy unless surveillance colonoscopy clinically indicated).
8. Subjects must have failed or be intolerant (as determined by the investigator) of at least one of the following treatments for UC: Oral corticosteroids, azathioprine or 6-mercaptopurine (6-MP), or anti-tumor necrosis factor (TNF) therapy, eg, infliximab or adalimumab.
9. Subjects currently receiving the following treatment regimens for UC are eligible providing they are on stable dose for designated period of time:
a. 5-ASA or sulfasalazine stable dose for at least 3 weeks prior to Day 1 and during the study treatment period.
b. Corticosteroids or equivalent at a stable dose for at least 2 weeks prior to Day 1 study visit (Prednisolone =25 mg/day, or equivalent). NOTE: Tapering of corticosteroids or equivalent may only commence at Week 8 (see “Concomitant Medications” section of the protocol).
c. Antibiotics (eg, metronidazole, rifaximin) stable dose for at least 2 weeks prior to Day 1 study visit and during the study treatment period ie, up to Week 8.
d. Rectally administered formulation of corticosteroids or 5-ASA stable dose for at least
2 weeks prior to Day 1 study visit and during the study treatment period ie, up to Week 8.
e. Methotrexate (up to 15 mg/week subcutaneously), azathioprine (up to 2.5 mg/kg/day) and 6-mercaptopurine (up to 1.5 mg/kg/day) stable for at least 2 months prior to Day 1 study visit and during the study treatment period, ie, up to Week 8.
NOTE: excluded medications include anti-TNF therapies used within 8 weeks of Day 1 study visit or cyclosporine, mycophenolate, or tacrolimus used within 4 weeks of Day 1 study visit as described in the exclusion criteria.
10.Subjects willing to use double contraception during the study treatment period and until completion of follow-up procedures ie, Week 52: (a) If the subject is a sexually active woman of childbearing potential, she and her male partner are required to simultaneously use 2 effective contraceptive methods as listed in Section 4.4.2 of the protocol. Female subjects who wish to use non-hormonal contraception must have done so for at least 14 days prior to the Day 1 study visit. (b) Non-vasectomized males with female partners of child bearing potential must be willing to use a condom in addition to ha
Exclusion criteria:
Subjects presenting with any of the following will not be included in the study:
1. Subjects who are investigational site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial.
2. Abnormal organ and marrow function as defined: (a) leukocytes <4,000/µL. (b) Platelets <150,000/µL. (c) AST (SGOT) or ALT (SGPT) >3x institutional upper limit of normal. (d) Bilirubin >upper institutional limit of normal. (e) Creatinine >1.2 mg/dL.
3. Diagnosis of indeterminate colitis, or clinical findings suggestive of Crohn’s disease, including Crohn’s enterocolitis, ischaemic colitis, radiation colitis, diverticular disease associated colitis as well as microscopic colitis.
4. Subjects with UC, which is confined to a proctitis defined as inflammation limited to less than 15 cm from the anal verge on a flexible sigmoidoscopy.
5. Subjects who meet Truelove-Witts criteria for severe UC. Diarrhea >6 times/day, bloody and any one of the items: (a) Hemoglobin 75% or below of normal value. (b) Evening temperature >37.5?C. (c) Pulse rate >90 beats/min. (d) ESR >30 mm/h.
6. Subjects who have received i.v. steroids or TPN or have been hospitalized due to UC within 3 weeks prior to screening.
7. Subjects displaying clinical signs of toxic megacolon, ischemic colitis or fulminant colitis.
8. Known allergies to bovine or porcine products, dextran or H1 blockers.
9. 9. Known intolerance to corticosteroids.
10. Subjects who have previously participated in any study of an allogeneic cell therapy, with the exception of erythrocyte transfusions.
11. Subjects who have received any investigational drug or device within 3 months (or as determined by the local requirement, whichever is longer) prior to Day 1 study visit.
12. History of symptomatic obstructive strictures, an ostomy, extensive bowel resection
(>100 cm) or short bowel syndrome.
13. History of bowel surgery within 6 months prior to Day 1 study visit.
14. Subject who have had surgery as a treatment for UC or, in the opinion of the investigator, are likely to require surgery within 16 weeks of informed consent.
15. Subjects diagnosed with primary sclerosing cholangitis.
16. Subjects with active inflammatory eye disease.
17. Subjects with spondylarthropathy and active musculoskeletal manifestation.
18. Subjects with active pyoderma gangrenosum or erythema nodosum lesions.
19. Subjects with clinically significant pulmonary disease (eg, subjects with COPD GOLD stage III or IV).
20. Subjects with NYHA class IV congestive heart failure.
21. Subjects with active systemic or severe local infections.
22. Fecal culture indicating presence of pathogenic infection; positive C. difficile toxin, or positive stool ova and parasite exam.
23. Subjects likely to require any type of surgery within 16 weeks from informed consent.
24. Known collection or abscess on MRI of the pelvis.
25. Pregnant or lactating women.
26. History of alcohol or drug abuse with less than 6 months of abstinence prior to Day 1 study visit.
27. Screening 12-lead ECG that demonstrates clinically relevant abnormalities which may affect subject safety or interpretation of study results.
28. Subjects with a temperature of 38?C (100.4?F) or higher at screening.
29. Subjects with malignancies or with a history of malignancies with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin.
30. Significant trauma or major surgery within 4 we

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Ulcerative Colitis
MedDRA version: 14.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Intervention(s)

Product Name: MultiStem
Product Code: PF-05285401
Pharmaceutical Form: Suspension for infusion
Current Sponsor code: PF-05285401
Other descriptive name: Multistem
Concentration unit: Other
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Product Name: MultiStem
Product Code: PF-05285401
Pharmaceutical Form: Suspension for infusion
Current Sponsor code: PF-05285401
Other descriptive name: Multistem
Concentration unit: Other
Concentration type: equal
Concentration number: 750 -
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Promiten
Pharmaceutical Form: Solution for injection
Other descriptive name: DEXTRAN 1 FOR INJECTION
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Main Objective: • To evaluate the safety and tolerability of intravenous doses of MultiStem in moderate-to-severe ulcerative colitis.

• To study the efficacy of a single intravenous dose of MultiStem in moderate-to-severe ulcerative colitis measured by an effect on endoscopic and rectal bleeding scores.

Primary end point(s): - Incidence and severity of adverse events (at Weeks, 4, 8, 12 and 16).

- Change from baseline of endoscopic score at Week 8 as measured by modified Baron score.

- Change from baseline of Mayo rectal bleeding sub-score at Week 4.

- Change from baseline of Mayo rectal bleeding sub-score at Week 8.

Secondary Objective: • To study the effect of a single intravenous dose of MultiStem on disease severity measured by total and partial Mayo score.

• To study the effect of repeat intravenous dose of MultiStem on disease measured by partial Mayo score and by rectal bleeding.

• To study the effect of intravenous doses of MultiStem on fecal calprotectin and C-reactive protein (CRP) levels.

Timepoint(s) of evaluation of this end point: Weeks 4, 8, 12 and 16.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Weeks 4, 8, 12 and 16.

Secondary end point(s): • Change from baseline of Mayo rectal bleeding sub-score at Weeks 12 and 16.
• Changes in laboratory measurements of safety and vital signs (at Weeks 4, 8, 12, and 16).
• Changes from baseline at Weeks 4, 8, 12 and 16 in the following biomarker levels: fecal calprotectin, CRP.
• Proportion of subjects with a Mayo rectal bleeding sub-score equal 0 at Weeks 4, 8, 12 and 16.
• Proportion of subjects in endoscopic remission at Week 8 (defined as subjects with a modified Baron endoscopic score equal 0).
• Proportions of subjects in clinical remission at Week 8 (defined as a total Mayo score of 2 points or lower, with no individual sub-score exceeding 1 point).
• Proportions of subjects with a decrease from baseline of at least one point in Mayo rectal bleeding sub-score at Weeks 4, 8, 12 and 16.
• Proportion of subjects with an endoscopic response at Week 8 (defined as a decrease in modified Baron endoscopic score from baseline of at least 2 points).
• Proportion of subjects with a clinical response at Week 8 (defined as a decrease in total Mayo score from baseline in Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the sub-score for rectal bleeding of at least 1 point or an absolute sub-score for rectal bleeding of 0 or 1).
• Changes from baseline in total Mayo score at Week 8.
• Changes from baseline in partial Mayo score at Weeks 4, 8, 12 and 16.
• Patient-reported rectal bleeding scores, to be modeled longitudinally up to and including Week 16.
• Changes in biopsy histology score at Week 8 (measured by Riley Index).

Secondary ID(s)

2010-022766-27-SE

B3041001

NCT01240915

Source(s) of Monetary Support

Pfizer Ltd