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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

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ClinicalTrials.gov Identifier: NCT05130983
Recruitment Status : Not yet recruiting
First Posted : November 23, 2021
Last Update Posted : December 22, 2021
Sponsor:
Information provided by (Responsible Party):
Direct Biologics, LLC

Tracking Information
First Submitted Date  ICMJE November 16, 2021
First Posted Date  ICMJE November 23, 2021
Last Update Posted Date December 22, 2021
Estimated Study Start Date  ICMJE January 1, 2022
Estimated Primary Completion Date January 1, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 16, 2021)
  • • To evaluate the feasibility of intravenous ExoFlo in subjects with moderately to severely active Crohn's disease who have failed or are intolerant to one or more monoclonal antibodies. [ Time Frame: 70 weeks ]
    • To evaluate the feasibility of intravenous ExoFlo in subjects with moderately to severely active Crohn's disease who have failed or are intolerant to one or more monoclonal antibodies.
  • monoclonal antibodies. • To evaluate the safety of intravenous ExoFlo in subjects with moderately to severely active Crohn's disease who have failed or are intolerant to one or more monoclonal antibodies. [ Time Frame: 70 weeks ]
    To evaluate the safety of intravenous ExoFlo in subjects with moderately to severely active Crohn's disease who have failed or are intolerant to one or more monoclonal antibodies.
    • To evaluate the feasibility of intravenous ExoFlo in subjects with moderately to severely active Crohn's disease who have failed or are intolerant to one or more monoclonal antibodies.
    • To evaluate the safety of intravenous ExoFlo in subjects with moderately to severely active Crohn's disease who have failed or are intolerant to one or more monoclonal antibodies.
    • To evaluate the feasibility of intravenous ExoFlo in subjects with moderately to severely active Crohn's disease who have failed or are intolerant to one or more monoclonal antibodies.
    • To evaluate the safety of intravenous ExoFlo in subjects with moderately to severely active Crohn's disease who have failed or are intolerant to one or more monoclonal antibodies.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 16, 2021)
  • • To evaluate the efficacy of intravenous ExoFlo in inducing clinical remission in subjects with moderately to severely active Crohn's disease who have failed or are intolerant to one or more monoclonal antibodies. [ Time Frame: 70 weeks ]
    • To evaluate the efficacy of intravenous ExoFlo in inducing clinical remission in subjects with moderately to severely active Crohn's disease who have failed or are intolerant to one or more monoclonal antibodies.
  • • To evaluate the efficacy of intravenous ExoFlo in inducing clinical response in subjects with moderately to severely active Crohn's disease who have failed or are intolerant to one or more monoclonal antibodies. [ Time Frame: 70 weeks ]
    • To evaluate the efficacy of intravenous ExoFlo in inducing clinical response in subjects with moderately to severely active Crohn's disease who have failed or are intolerant to one or more monoclonal antibodies.
  • • To evaluate the efficacy of intravenous ExoFlo in improving disease-specific health-related quality of life. [ Time Frame: 70 weeks ]
    • To evaluate the efficacy of intravenous ExoFlo in improving disease-specific health-related quality of life.
  • • To evaluate the pharmacokinetics and pharmacodynamics of ExoFlo therapy, including changes in C-reactive protein (CRP), fecal calprotectin, fecal lactoferrin, and other pharmacodynamic biomarkers. [ Time Frame: 70 weeks ]
    • To evaluate the pharmacokinetics and pharmacodynamics of ExoFlo therapy, including changes in C-reactive protein (CRP), fecal calprotectin, fecal lactoferrin, and other pharmacodynamic biomarkers.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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: 70 weeks Single or Multi-Site: Single site Primary Objectives: • To evaluate the feasibility of intravenous ExoFlo in subjects with moderately to severely active Crohn's disease who have failed or are intolerant to one or more monoclonal antibodies.

• To evaluate the safety of intravenous ExoFlo in subjects with moderately to severely active Crohn's disease who have failed or are intolerant to one or more monoclonal antibodies.

Secondary Objectives: • To evaluate the efficacy of intravenous ExoFlo in inducing clinical remission in subjects with moderately to severely active Crohn's disease who have failed or are intolerant to one or more monoclonal antibodies.

  • To evaluate the efficacy of intravenous ExoFlo in inducing clinical response in subjects with moderately to severely active Crohn's disease who have failed or are intolerant to one or more monoclonal antibodies.
  • To evaluate the efficacy of intravenous ExoFlo in improving disease-specific health-related quality of life.
  • To evaluate the pharmacokinetics and pharmacodynamics of ExoFlo therapy, including changes in C-reactive protein (CRP), fecal calprotectin, fecal lactoferrin, and other pharmacodynamic biomarkers.

Number of Subjects 10

Diagnosis and Main Inclusion Criteria: Subjects must have colitis, ileitis, or ileocolitis previously confirmed at any time in the past by radiography, histology, and/or endoscopy, and must allow a 8-week washout for prior TNF antagonist use.

Study Product, Dose, Route, Regimen: Arm 1: IV administration of study agent at Day 0, Day 2, Day 4, Week 2, Week 6 and every 8 weeks thereafter to week 46 (n=5), (total # doses = 10).

Arm 2: IV administration of study agent at Day 0, Day 2, Day 4, Week 2, Week 6 and every 4 weeks thereafter to week 46 (n=5), (total # doses = 15).

Statistical Methodology: This is a safety study with exploratory assessment of efficacy. The study has insufficient power to confirm efficacy. All assessments of efficacy will be exploratory for the purpose of hypothesis-generation in larger sample sizes.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Crohn Disease
  • IBD - Irritable Bowel Disease
Intervention  ICMJE Drug: Bone Marrow MSC Derived Extracellular Vesicle Isolate
ExoFlo 15ml, IV
Study Arms  ICMJE
  • Experimental: 15ml of ExoFlo at Day 0, 2, 4 Week 2, 6, and every 8 weeks after that to week 46
    Arm 1: IV administration of study agent at Day 0, Day 2, Day 4, Week 2, Week 6 and every 8 weeks thereafter to week 46 (n=5), (total # doses = 10).
    Intervention: Drug: Bone Marrow MSC Derived Extracellular Vesicle Isolate
  • Experimental: 15ml of ExoFlo at Day 0, 2, 4 Week 2, 6, and every 4 weeks after that to week 46
    Arm 2: IV administration of study agent at Day 0, Day 2, Day 4, Week 2, Week 6 and every 4 weeks thereafter to week 46 (n=5), (total # doses = 15).
    Intervention: Drug: Bone Marrow MSC Derived Extracellular Vesicle Isolate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: November 16, 2021)
10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 1, 2024
Estimated Primary Completion Date January 1, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 1. Males and females 18-75 years of age 2. Crohn's colitis of at least 6 months duration with medically refractory symptoms who has failed one anti-TNF therapy (failed to have improvement of disease while receiving at least one monoclonal antibody for 8 weeks duration prior to enrollment, including Infliximab, Adalimumab, Certolizumab, Golimumab, Vedolizumab, Ustekinumab, and Tofacitinib), with a next step of subtotal colectomy or escalation in medical management 3. Patient with moderately to severely active Crohn's disease as defined by a CDAI score >220 and SES-CD score ≥ 6 (or ≥4 isolated ileal disease) 4. 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

    1. 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.
    2. If AZA, 6-MP, or MTX has been recently discontinued, it must have been stopped for at least 4 weeks.
    3. 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.
    4. If receiving budesonide, the dose must have been stable for at least 2 weeks.
    5. If oral 5-ASA compounds or oral corticosteroids (including budesonide) have been recently discontinued, they must have been stopped for at least 2 weeks.

      5. The following medications/therapies must have been discontinued before first administration of study agent:

    1. TNF-antagonist therapy (e.g., infliximab, etanercept, certolizumab, adalimumab, golimumab), vedolizumab, ustekinumab for at least 8 weeks.
    2. Cyclosporine, tacrolimus, or sirolimus, for at least 4 weeks.
    3. 6-thioguanine (6-TG) must have been discontinued for at least 4 weeks.
    4. 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.
    5. 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.
    6. Parenteral corticosteroids for at least 2 weeks.
    7. Total parenteral nutrition (TPN) for at least 2 weeks.
    8. Antibiotics for the treatment of CD (e.g., ciprofloxacin, metronidazole, or rifaximin) for at least 2 weeks.

      6. No colonic dysplasia and malignancy as ruled out by colonoscopy within 90 days of first ExoFlo delivery 7. Ability to comply with protocol 8. Competent and able to provide written informed consent 9. Stated willingness to comply with all study procedures and availability for the duration of the study 10. If patient is of reproductive capacity, willing to use adequate birth control measures while they are in the study

Exclusion Criteria:

  • 1. Inability to give informed consent. 2. 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.

    3. Patients with confirmed HIV, Hepatitis B, or Hepatitis C infections 4. Abnormal AST or ALT at screening defined as AST >100 or ALT > 100 5. Abnormal basic laboratory values with the following cut-offs:

    1. Alkaline phosphate >200
    2. WBC >13
    3. Hemoglobin <7
    4. Platelets <50 or > 1 million
    5. eGRF < 60
    6. HbA1C > 8% 6. Subjects with abnormal coagulation studies:

    a. Prothrombin time (PT) > 1.5 times the upper limits of normal b. Partial thromboplastin time (PTT) > 1.5 times the upper limits of normal c. International normalized ratio (INR) > 1.5 times the upper limits of normal 7. Subjects with hyperbilirubinemia and evidence of liver disease as defined by AST > 100 or ALT > 100 or PT > 1.5 times the upper limits or normal or PT/INR > 1.5 time the upper limits of normal.

    8. Subjects with abnormal vital signs as defined by:

    1. Systolic blood pressure >160 or <90 mmHg
    2. Diastolic blood pressure >90 or <60 mmHg
    3. Pulse <60 or >105 bpm
    4. Respiratory Rate <9 and >25 breaths per minute
    5. Temperature: >100.4 degrees Fahrenheit
    6. SpO2 : <92% 9. History of cancer including melanoma (with the exception of localized skin cancers) within 5 years of study enrollment 10. Investigational drug within one year of study enrollment 11. Pregnant or breast feeding. 12. If patient is of reproductive capacity, unwilling to use adequate birth control measures while they are in the study 13. Fulminant colitis requiring emergency surgery 14. Concurrent active clostridium difficile infection of the colon 15. Concurrent CMV infection of the colon 16. Evidence of colonic perforation 17. Massive hemorrhage from the colon requiring emergent surgery 18. Ulcerative colitis or indeterminate colitis 19. Microscopic, ischemic or infectious colitis 20. Neoplasia of the colon on preoperative biopsy 21. Presence of an ostomy 22. Three or more prior small bowel resections 23. Previous colonic resection 24. Colonic stricture that unable to pass an adult colonoscope 25. Active or latent tuberculosis 26. Unable to wean off corticosteroids 27. Patients with primary sclerosing cholangitis 28. Patients with history of or current evidence of alcohol or drug abuse or dependence, recreational use of illicit drug or prescription medications, or have use of medical marijuana within 90 days of study entry 29. Patients with known allergy to local anesthetics 30. Patients taking anticoagulant medications (e.g. warfarin, heparin) or clopidogrel (Plavix) to reduce the risk of bleeding/ hemarthrosis 31. Individuals with inherited or acquired hypercoagulable states, history of thromboembolic events or bleeding disorders 32. Electrocardiogram demonstrating cardiac arrhythmia, except for sinus tachycardia within the predefined limit of no greater than 105 bpm.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Heidi Moran 800-791-1021 hmoran@directbiologics.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05130983
Other Study ID Numbers  ICMJE DB-EF-CROHNS-0004
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Direct Biologics, LLC
Study Sponsor  ICMJE Direct Biologics, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Vikram Sengupta, MD Direct Biologics
PRS Account Direct Biologics, LLC
Verification Date December 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP