Clinical Study of Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Moderate and Severe Crohn's Disease

NCT05262829 | Unknown

• 1 other identifier: DFSC-2021(CR)-07
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-arm, open-ended study to evaluate the efficacy and safety of human umbilical cord MSCs in the treatment of refractory moderate-to-severe Crohn's disease. The study protocol is either MSC injection into the patient's diseased intestinal mucosa or intravenous MSC injection + MSC injection into the patient's diseased intestinal mucosa. Follow-up time points were pre-treatment (week 0), week 4, week 8, week 12, and week 24 post-treatment, and the primary evaluation at follow-up was the number of subjects with clinical and endoscopic response or remission.

Conditions

Crohn Disease

Keywords

Human Umbilical Cord Mesenchymal Stem Cells; Crohn Disease

Outcome Measures

Primary Outcomes (2)

• Crohn's disease activity index score

  The Crohn's Disease Activity Index (CDAI) was used to assess the severity of CD disease, and a CDAI \<150 was considered clinically remitting; a decrease in CDAI ≥70 was considered clinically effective, also known as clinical response.

  Changes from baseline to week 4, week 8, week 12 and week 24 after stem cell treatment.

• simplified endoscopic score for Crohn's disease

  Endoscopic response was defined as at least 50% improvement in the simplified endoscopic score for Crohn's disease (SES-CD) from baseline, and endoscopic remission was defined as a SES-CD score ≤2.

  Changes from baseline to week 4, week 8, week 12 and week 24 after stem cell treatment.

Secondary Outcomes (5)

• Inflammatory Bowel Disease Questionnaire

  Changes from baseline to week 4, week 8, week 12 and week 24 after stem cell treatment.

• Albumin

  Changes from baseline to week 4, week 8, week 12 and week 24 after stem cell treatment.

• Hemoglobin

  Changes from baseline to week 4, week 8, week 12 and week 24 after stem cell treatment.

• Fecal calprotectin

  Changes from baseline to week 4, week 8, week 12 and week 24 after stem cell treatment.

• body mass index (BMI)

  Changes from baseline to week 4, week 8, week 12 and week 24 after stem cell treatment.

Study Arms (1)

MSCs local treatment group/combined treatment group

EXPERIMENTAL

In the local treatment group, 60 million umbilical cord MSCs were injected into the diseased intestinal mucosa on the first day. In the combined treatment group, 60 million umbilical cord MSCs were injected into the diseased intestinal mucosa on the first day; on the second day, 1 million cells/kg of body weight were administered intravenously.

Biological: Human Umbilical Cord Mesenchymal Stem Cells

Interventions

Human Umbilical Cord Mesenchymal Stem Cells BIOLOGICAL

MSCs treatment by intestinal submucosal injection/MSCs treatment by intravenous drip + MSCs treatment by intestinal submucosal injection

MSCs local treatment group/combined treatment group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects aged between 18 and 70 years (including borderline values), of either sex.
• Subjects with a comprehensive diagnosis of Crohn's disease for more than 3 months based on the patient's clinical presentation, endoscopy, imaging and pathology, with reference to the Consensus Opinion on the Diagnosis and Treatment of Inflammatory Bowel Disease in China (2018-Beijing).
• Failure to respond to existing conventional therapy, or to primary or secondary treatment with TNF alpha monoclonal antibody, vedolizumab or ustekinumabd.
• Current Crohn's disease with a Crohn's Disease Activity Index (CDAI) score ≥ 220 and ≤ 450.
• Evidence of active inflammation and ulceration confirmed by endoscopy during screening.
• Subjects must be free of active, latent, or undertreated Mycobacterium tuberculosis infection.
• All women of childbearing potential and all men must be willing to use at least one highly effective method of contraception at the time of signing the consent form and throughout the study period until 1 month after the last dose of study drug.
• Subjects who are willing and able to undergo treatment and follow-up, laboratory tests, and other study procedures as planned.
• Subjects who are able to sign (and date) an informed consent form indicating that the subject has been informed of all relevant parts of the study
• Subjects receiving non-disabling combination therapy for any reason must maintain a stable treatment regimen, defined as no stem cell therapy given or no dose change within 7 days or 5 half-lives (whichever is longer) prior to the initial stem cell injection.

You may not qualify if:

• Presence of a complication of Crohn's disease, such as short bowel syndrome or any other manifestation that might be expected to require surgery, that prevents the use of CDAI to assess treatment response, or that might confound the assessment of the efficacy of MSC therapy.
• Subjects with evidence of pathogenic intestinal infection. Subjects with Clostridium difficile or other intestinal infections within 30 days of endoscopic screening, or subjects who screen positive for C. difficile toxin assay or other pathogens.
• Subjects with total bilirubin, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above 2 times the upper limit of normal at the screening visit. Patients with cirrhosis will be excluded.
• Subjects with eGFR ≤ 60 mL/min (as calculated by Cockcroft-Gault) or patients receiving hemodialysis.
• Subjects with a current or clinically significant infection within 1 month prior to baseline, or history of more than one prior occurrence of herpes zoster, disseminated zoster (one occurrence) and other infections that the investigator believes may be exacerbated by participation in the study, or any infection requiring antimicrobial therapy within 2 weeks of screening.
• Subjects who may currently be receiving any live virus vaccination or who have received any live virus vaccination within 8 weeks prior to baseline.
• Subjects with a first-degree relative with a hereditary immunodeficiency.
• History of any lymphoid proliferative disease (e.g., EBV-associated lymphoid proliferative disease), lymphoma, leukemia, myeloproliferative disease, multiple myeloma, or signs and symptoms suggestive of presenting lymphoid system disease.
• Subjects who have received prior treatment with any lymphocyte depleting agent/therapy. Subjects with prior treatment with rituximab or other selective B lymphocyte depleting agents, but who have not received such treatment for at least 1 year prior to baseline, are eligible for the study.
• Pregnant or lactating women or female subjects who are pregnant during planned enrollment in the study.
• Prior history of alcohol or drug abuse and less than 6 months of abstinence prior to baseline.
• Subjects with clinically relevant abnormalities confirmed by 12-lead ECG during the screening period that would affect their safety if enrolled in this study or affect the interpretation of the study results.
• Subjects who have donated more than 500 mL of blood in the 2 months prior to baseline.
• Subjects who have experienced major trauma or undergone major surgery within 4 weeks of the screening visit.
• Subjects with a body temperature ≥38°C during the screening period or baseline period.

Sponsors & Collaborators

• Shanghai East Hospital: lead

Study Sites (1)

Shanghai East Hospital

Shanghai, Pudong New Area, China

RECRUITING

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Lan Zhong, MD

  Shanghai East Hospital

  STUDY DIRECTOR

Central Study Contacts

Lan Zhong, MD

CONTACT

+86-13162099450; lanzhong@tongji.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2022
• First Posted: March 2, 2022
• Study Start: February 28, 2022
• Primary Completion: August 31, 2024
• Study Completion: January 31, 2025
• Last Updated: February 17, 2023

Record last verified: 2023-02

Locations

CN (1)