Study of ExoFlo for the Treatment of Medically Refractory Crohn's Disease

NCT05130983 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: DB-EF-CD-01
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief Summary

Protocol Summary

• Title: A Phase I study of ExoFlo, an ex vivo culture-expanded adult allogeneic bone marrow mesenchymal stem cell derived extracellular vesicle isolate product, for the treatment of medically refractory Crohn's disease.
• Short Title: ExoFlo for Crohn's Disease
• Phase: 1
• Methodology: Open label
• Study Duration: 24 months
• Subject Participation: 58 weeks
• Single or Multi-Site: Multi-Site

Conditions

Crohn Disease; Inflammatory Bowel Diseases

Keywords

ExoFlo; Inflammatory Bowel Diseases; Crohn's Disease; Extracelluar Vesicle

Outcome Measures

Primary Outcomes (2)

• Safety of intravenous ExoFlo in subjects with medically refractory Crohn's disease who have failed, or are intolerant, or have a contraindication to one or more monoclonal antibodies.

  Safety will be defined as lack of serious adverse events or adverse advents related to treatment with the study therapeutic.

  58 Weeks

• Feasibility of intravenous ExoFlo in subjects with medically refractory Crohn's disease who have failed, or are intolerant, or have a contraindication to one or more monoclonal antibodies.

  The study will not be considered feasible if more than three subjects are not capable of receiving the ExoFlo based on ability to release or deliver the cells. If a subject misses any single dose of ExoFlo, they will be withdrawn and not replaced.

  58 Weeks

Secondary Outcomes (6)

• To evaluate the efficacy of intravenous ExoFlo in inducing clinical remission at week 6 and week 46.

  Week 6 and Week 46

• To evaluate the efficacy of intravenous ExoFlo in inducing clinical response at week 6 and week 46.

  Week 6 and Week 46

• To evaluate endoscopic remission and endoscopic response.

  58 Weeks

• To evaluate the efficacy of intravenous ExoFlo in improving disease-specific health-related quality of life.

  58 Weeks

• To evaluate the pharmacokinetics and pharmacodynamics of ExoFlo therapy, including changes in C-reactive protein (CRP) and fecal calprotectin.

  58 Weeks

Study Arms (1)

15ml at Day 0, 2, 4, 30 ml at Week 2, Week 6, and every 4 weeks after to week 46

EXPERIMENTAL

IV administration of 15 mL study agent at Day 0, Day 2, Day 4 and 30 mL at Week 2, Week 6 and every 4 weeks thereafter to week 46 (total # doses = 15).

Biological: ExoFlo

Interventions

ExoFlo BIOLOGICAL

Intravenous administration of bone marrow mesenchymal stem cell derived extracellular vesicles

15ml at Day 0, 2, 4, 30 ml at Week 2, Week 6, and every 4 weeks after to week 46

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females 18-75 years of age
• Crohn's colitis of at least 6 months duration with medically refractory symptoms who has failed one monoclonal antibody therapy (failed to have improvement of disease while receiving at least one monoclonal antibody for 8 weeks duration prior to enrollment, including, but not limited to, Infliximab, Adalimumab, Certolizumab, Golimumab, Vedolizumab, Ustekinumab and Tofacitinib), or is intolerant, or has a contraindication to monoclonal antibody therapy with a next step of subtotal colectomy or escalation in medical management
• Patient with medically refractory Crohn's disease as defined by a CDAI score ≥150 and/or SES-CD score ≥ 3
• Exposure to corticosteroids, 5-ASA drugs, thiopurines, methotrexate, anti-TNF therapy, anti-integrin and anti-interleukin in the past are permitted but a washout period of 8 weeks for any monoclonal antibody is necessary.
• If receiving conventional immunomodulators (ie, AZA, 6-MP, or MTX), must have been taking them for ≥12 weeks, and on a stable dose for at least 4 weeks prior to receiving the first dose of the study drug.
• If AZA, 6-MP, or MTX has been recently discontinued, it must have been stopped for at least 4 weeks prior to receiving the first dose of study drug.
• If receiving oral 5-ASA compounds, the dose must have been stable for at least 4 weeks. If receiving oral corticosteroids, the dose must be ≤20 mg/day prednisone or its equivalent and must have been stable for at least 4 weeks prior to receiving the first dose of study drug.
• If receiving budesonide, the dose must have been stable for at least 2 weeks prior to receiving the first dose of study drug.
• If oral 5-ASA compounds or oral corticosteroids (including budesonide) have been recently discontinued, they must have been stopped for at least 2 weeks prior to receiving the first dose of study drug.
• The following medications/therapies must have been discontinued before first administration of study agent:
• TNF-antagonist therapy (e.g., infliximab, etanercept, certolizumab, adalimumab, golimumab), vedolizumab, ustekinumab for at least 8 weeks.
• Cyclosporine, tacrolimus, or sirolimus, for at least 4 weeks.
• thioguanine (6-TG) must have been discontinued for at least 4 weeks.
• Rectal corticosteroids (i.e., corticosteroids \[including budesonide\] administered to the rectum or sigmoid colon via foam or enema or suppository) for at least 2 weeks.
• Rectal 5-ASA compounds (i.e., 5-ASAs administered to the rectum or sigmoid colon via foam or enema or suppository) for at least 2 weeks.

You may not qualify if:

• Inability to give informed consent.
• Clinically significant medical conditions within the six months before administration of ExoFlo: e.g., myocardial infarction, active angina, congestive heart failure or other conditions that would, in the opinion of the investigators, compromise the safety of the patient.
• Patients with confirmed HIV, Hepatitis B, or Hepatitis C infections
• Abnormal AST or ALT at screening defined as AST \>100 or ALT \> 100
• Abnormal basic laboratory values with the following cut-offs:
• Alkaline phosphate \>200
• WBC \>13
• Hemoglobin \<7
• Platelets \<50 or \> 1 million
• eGFR \< 60
• HbA1C \> 8%
• Subjects with abnormal coagulation studies:
• Prothrombin time (PT) \> 1.5 times the upper limits of normal
• Partial thromboplastin time (aPTT) \> 1.5 times the upper limits of normal
• International normalized ratio (INR) \> 1.5 times the upper limits of normal

Sponsors & Collaborators

• Direct Biologics, LLC: lead

Study Sites (2)

Direct Biologics Investigational Site

Los Angeles, California, 90048, United States

Location

Direct Biologics Investigational Site

New York, New York, 10016, United States

Location

Related Links

• Direct Biologics, LLC

MeSH Terms

Conditions

Crohn Disease; Inflammatory Bowel Diseases

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Bill Arana

  Direct Biologics, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2021
• First Posted: November 23, 2021
• Study Start: January 23, 2023
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: February 11, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)