Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Fistulas in Patients with Refractory Perianal Crohn’s Disease - allo bmMSCs CD fistula

• Register: EUCTR
• Last refreshed on: 16 February 2015
• Main ID: EUCTR2009-015680-14-NL
• Date of registration: 27/07/2010
• Prospective Registration: No
• Primary sponsor: Leiden University Medical Center
• Public title: Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Fistulas in Patients with Refractory Perianal Crohn’s Disease - allo bmMSCs CD fistula
• Scientific title: Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Fistulas in Patients with Refractory Perianal Crohn’s Disease - allo bmMSCs CD fistula
• Date of first enrolment: 18/05/2010
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-015680-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: surgical approach without intralesional injection of IMP

Countries of recruitment

Netherlands

Key inclusion & exclusion criteria

Inclusion criteria:
a) Men and women ? 18 years of age;
b) Patient must have had CD (for at least 3 months from the time of initial diagnosis). The diagnosis of CD must have been confirmed by endoscopic and histologic evidence;
c) CDAI score of <250 at screening and baseline;
d) Peri-anal fistulas must be refractory to conventional medical therapy. Which means that at some time during the course of the disease, patient must have received both steroids and immunosuppressive agents (for example, azathioprine, 6-mercaptopurine, methotrexate, or infliximab) which did not result in an adequate response to treatment;
e) Patients with previous surgical attempts to eradicate perianal fistulas are eligible for inclusion as are patients with setons in situ. Setons will be removed during the surgical procedure.
f) Patients included in the study might be receiving 5-aminosalicylic acid (5-ASA), steroids, azathioprine, 6-mercaptopurine (6-MP), methotrexate, or any similar drug at the time of enrolment and is allowed to have a history of infliximab treatment, provided the following conditions are fulfilled at screening:
? The dose of 5-ASA (both oral and rectal) must have been stable for at least 4 weeks prior to enrolment.
? The dose of steroids must be stable for at least 4 weeks prior to enrolment.
? The dose of immunosuppressants (for example azathioprine, 6MP, or methotrexate) must have been stable for at least 8 weeks prior to enrolment and the patient on therapy for at least three months prior to enrolment.
? The last dose of infliximab or other anti-TNF drug is > 8 weeks prior to enrolment;
g) No need for immediate surgery (obstruction, strictures or abscess);
h) If female and of child-bearing age, patient must be non-pregnant, non-breastfeeding, and use adequate contraception;
i) Patient is willing to participate in the study and has signed the informed consent. Consent must be obtained prior to any study procedure.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
a) Patients with evidence of acute peri-anal infection, presence of peri-anal abscesses larger than 2 cm, and anal or rectal stricture;
b) Patients with evidence of any infections needing antibiotic treatment.
c) Rectovaginal fistulas, or complex peri-anal fistulas with more than two internal openings;
d) Patients suffering from renal- or hepatic failure.
e) Use of any investigational drug within 1 month prior to screening or within 5 half-lives of the investigational agent, whichever is longer;
f) Patient is allergic to gadolinium (MRI contrast agent);
g) Patient with severe renal insufficiency defined as patients with a glomerular filtration rate (GFR) below 60 mL/min/1.73 m2. GFR = 186.3 x (serum creatinine)-1.154 x (age in years)-0.203 x 1.212 (if patient is black) x 0.742 (if female);
h) Due to the high strength electromagnetic fields that will be used during MRI there is a risk of interference with any metallic implants in the body. The following conditions will disqualify patients from having an MRI and will be excluded from this study:
? electronically, magnetically, and mechanically activated implants
? ferromagnetic or electronically operated stapedial implants
? cardiac pacemakers/carotid sinus pacemaker implant
? hemostatic clips
? metallic splinters in the orbit
? insulin pumps and nerve stimulators
? lead wires or similar wires
? metal intrauterine device
i) Change in concomitant medication:
? Steroids must be stable for at least 4 weeks prior to enrolment,
? 5-ASA should be on a stable dose > 4 weeks prior to enrolment,
? Immunosuppressants (e.g. azathioprine, 6MP or methotrexate) should be on a stable dose > 8 weeks prior to enrolment,
? Infliximab or other anti-TNF antibody therapy should not be administered < 8 weeks prior to enrolment.
j) Clausterphobia;
k) Documented HIV infection. Active hepatitis B, hepatitis C or TB;
l) Patients who currently have or who have had an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening;
m) Serious infections (such as pneumonia or pyelonephritis) in the previous 3 months. Less serious infections (such as acute upper respiratory tract infection [colds] or simple urinary tract infection) need not be considered exclusions at the discretion of the investigator;
n) Malignancy within the past 5 years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence);
o) History of lymphoproliferative disease including lymphoma;
p) Patient is unwilling or unable to comply with the study procedures.



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

Health Condition(s) or Problem(s) studied

single or multiple draining perianal fistulas as a result of Crohn's Disease
MedDRA version: 12.1 Level: LLT Classification code 10011401 Term: Crohn's disease

Intervention(s)

Product Name: Bone Marrow Derived Mesenchymal Stem cells (MSCs)
Product Code: NA
Pharmaceutical Form: Injection*

Primary Outcome(s)

Primary end point(s): 1. Safety will be assessed in terms of the incidence of adverse events and changes in vital signs and routine laboratory measures. Patients will be monitored for adverse events during MSC administration and at each study visit according to WHO criteria.

2. Patients will undergo MRI at baseline and 12 weeks after bmMSC administration. MRI classifications will be assessed by a blinded independent radiologist. The reduction in the number of draining fistulas is defined as absence of discharge upon pressure and absence of collections of =2 cm directly related to the treated fistulas tracts as measured by MRI.

Main Objective: 1. To assess the safety (incidence of intervention related [serious] adverse events) and tolerability of the surgical intervention alone or the surgical intervent with local administration of different doses of allogeneic MSCs in fistula tracts of patients with refractory CD.
2. To document the efficacy of different doses of allogeneic bmMSCs in the induction of response for active fistulizing CD.

Secondary Objective: At 12 weeks
1. To assess changes in the Crohn’s Disease Activity Index (CDAI), the Perianal Disease Activity Index (PDAI) and the adapted Vaizey fecal incontinence score before and after MSC treatment;
2. To compare endoscopic changes before and after local bmMSC treatment using the Crohn’s Disease Endoscopic Index of Severity (CDEIS) and simplified endoscopic activity score for Crohn’s disease (SES-CD);
3. To evaluate the effect of local treatment with autologous bmMSCs on the quality of life of patients with fistulizing CD using the short Inflammatory Bowel Disease Questionnaire (sIBDQ) and Short Form (SF)-36 score;
4. To summarize the changes from baseline compared to 12 weeks in serum CRP.

At 12 and 24 weeks
5. To assess the incidence of surgical intervention and infections.

Secondary ID(s)

allo bmMSCs CD fistula