Mesenchymal Stromal Cells for the treatment of Ulcerative Colitis

• Register: EUCTR
• Last refreshed on: 30 April 2018
• Main ID: EUCTR2017-003524-75-NL
• Date of registration: 19/02/2018
• Prospective Registration: Yes
• Primary sponsor: Leiden University Medical Center
• Public title: Mesenchymal Stromal Cells for the treatment of Ulcerative Colitis
• Scientific title: Allogeneic Bone Marrow Derived Mesenchymal Stromal Cells for the Treatment of Refractory Proctitis in Ulcerative Colitis - BMMSCproctitis
• Date of first enrolment: 27/03/2018
• Target sample size: 14
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-003524-75
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: First seven patients will be treated with the same dose, next seven patients with double dose If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Netherlands

Contacts

• Name: A.E. van der Meulen - de Jong
• Affiliation: Leiden University Medical Center/ Principal Investigator

• Name: A.E. van der Meulen - de Jong
• Affiliation: Leiden University Medical Center/ Principal Investigator

Key inclusion & exclusion criteria

Inclusion criteria:
a) Men and women = 18 years of age;
b) Patient must have UC confirmed by endoscopic and histologic evidence;
c) Inflammation must be limited to the rectum (up to 15 cm beyond the anal verge), confirmed by endoscopy maximum 3 months before baseline (slight inflammation in other parts of the colon is accepted with a maximum Mayo Score of 1);
d) Moderate to severe proctitis indicated by a Mayo Score of 2 or 3;
e) Proctitis must be refractory to conventional medical therapy. Which means that at some time during the course of the disease, patient must have received rectal 5-ASA therapy and rectal corticosteroid therapy for at least 4 weeks which did not result in an adequate response to treatment;
f) If treated with rectal therapy, therapy must be stopped two weeks before endoscopic implantation of MSCs and only restarted after 6 weeks;
g) If treated with oral 5-ASA therapy, dose must be stable for 4 weeks prior to study entry and remain on same dose during the first 6 weeks after MSC treatment;
h) If treated with oral corticosteroids, dose must be stable for 2 weeks prior to study entry and remain on same dose during the first 6 weeks after MSC treatment;
i) If treated with 6-mercaptopurine, methotrexate, azathioprine, vedolizumab or anti-TNF therapy patients must have been on medication for 3 months and a stable dose for 2 months prior to study entry and remain on same dose during the first 6 weeks after MSC treatment;
j) If female and of child-bearing age, patient must be non-pregnant, non-breastfeeding, and use adequate contraception;
k) 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 12
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion criteria:
a) Patients suffering from renal- or hepatic failure;
b) Use of any investigational drug within 1 month prior to screening or within 5 half-lives of the investigational agent, whichever is longer;
c) Positive stool culture for enteric pathogens (salmonella, shigella, and campylobacter), positive C. difficile toxin, or positive stool ova and parasite exam;
d) All active infections requiring treatment;
e) Patients who had tuberculosis or an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis) within 6 months prior to screening;
f) 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);
g) Any dysplasia in the colon in the past 5 years;
h) Very severe proctitis; expected to result in hospitalization/ surgery within 3 months;
i) Previous treatment with allogeneic MSCs;
j) Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study;
k) 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

Ulcerative Colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: Mesenchymal stromal cells
Product Code: MSC
Pharmaceutical Form: Suspension for injection in pre-filled syringe
INN or Proposed INN: n.a.
CAS Number: n.a.
Current Sponsor code: Freshly harvested_BMMSC_P3
Other descriptive name: MESENCHYMAL CELLS
Concentration unit: Other
Concentration type: equal
Concentration number: 10000000 -

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 6.
After the first 7 patients there will be an interim analyses. The results will be reviewed by the DSMB.

Main Objective: To assess the safety, tolerability and feasibility of endoscopic injected MSCs in the distal colon of patients with refractory proctitis after 6 weeks.

Primary end point(s): Local MSC therapy in patients with UP will be found safe when no SAEs, related to endoscopic MSC therapy, are reported in the 14 patients treated with MSC therapy after 6 weeks. Evaluation of tolerability will be based upon AE monitoring, measurements of vital signs as well as the patient’s and investigator’s global judgment of tolerability. The therapy will be found tolerable when >80% of the patients after the treatment procedure and at week 6 will define the adverse events and procedure as tolerable. Evaluation of the feasibility will be based upon practical problems and complaints that are encountered in the execution of the study. The therapy will be found feasible when there are <20% practical dropouts.

Secondary Objective: At 2, 6 and 24 weeks

1. To assess changes in the Mayo Score (appendix C) before and after BMMSC treatment; as an indication of efficacy.

At 2, 6, 12 and 24 weeks

2. To assess changes in patient-reported outcome measures (PROMs) using the mHealth index (appendix D) [71].
3. To summarize the changes in serum c-reactive protein (CRP) and fecal calprotectin.

At 6 and 24 weeks
4. To compare histologic disease activity before and after local BMMSC treatment using the Geboes score (appendix E).
5. To evaluate the effects of this intervention on immunological parameters and local MSC persistence.

At 6, 12, 24 weeks

6. To evaluate the effect of local treatment with allogeneic BMMSCs on the quality of life using the 12-item Short Form Health Survey (SF-36) (appendix F) and the short Inflammatory Bowel Disease Questionnaire (sIBDQ) (appendix G).

Secondary Outcome(s)

Secondary end point(s): At 2, 6 and 24 weeks

1. To assess changes in the Mayo Score (appendix C) before and after BMMSC treatment; as an indication of efficacy.

At 2, 6, 12 and 24 weeks

2. To assess changes in patient-reported outcome measures (PROMs) using the mHealth index (appendix D) [71].
3. To summarize the changes in serum c-reactive protein (CRP) and fecal calprotectin.

At 6 and 24 weeks
4. To compare histologic disease activity before and after local BMMSC treatment using the Geboes score (appendix E).
5. To evaluate the effects of this intervention on immunological parameters and local MSC persistence.

At 6, 12, 24 weeks

6. To evaluate the effect of local treatment with allogeneic BMMSCs on the quality of life using the Short Form Health Survey (SF-36) (appendix F) and the short Inflammatory Bowel Disease Questionnaire (sIBDQ) (appendix G).

Timepoint(s) of evaluation of this end point: Week 2, 6, 12 and 24

Secondary ID(s)

LUMC-MDLZ-MSCIBD03

Source(s) of Monetary Support

Leiden University Medical Center