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Study of ExoFlo for the Treatment of Medically Refractory Ulcerative Colitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05176366
Recruitment Status : Not yet recruiting
First Posted : January 4, 2022
Last Update Posted : January 5, 2022
Sponsor:
Information provided by (Responsible Party):
Direct Biologics, LLC

Brief Summary:
A Phase I study of ExoFlo, an ex vivo culture-expanded adult allogeneic bone marrow mesenchymal stem cell derived extracellular vesicle product, for the treatment of medically refractory ulcerative colitis

Condition or disease Intervention/treatment Phase
Ulcerative Colitis Drug: ExoFlo Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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 Ulcerative Colitis
Estimated Study Start Date : January 1, 2022
Estimated Primary Completion Date : January 1, 2024
Estimated Study Completion Date : March 1, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 15ml of ExoFlo at Day 0, 2, 4 Week 2, 6, and every 8 weeks after that to week 46
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).
Drug: ExoFlo
A Phase I study of ExoFlo, an ex vivo culture-expanded adult allogeneic bone marrow mesenchymal stem cell derived extracellular vesicle product, for the treatment of medically refractory ulcerative colitis

Experimental: 15ml of ExoFlo at Day 0, 2, 4 Week 2, 6, and every 4 weeks after that to week 46
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).
Drug: ExoFlo
A Phase I study of ExoFlo, an ex vivo culture-expanded adult allogeneic bone marrow mesenchymal stem cell derived extracellular vesicle product, for the treatment of medically refractory ulcerative colitis




Primary Outcome Measures :
  1. Number of subjects who tolerate intravenous ExoFlo in those subjects with moderately to severely active Ulcerative colitis who have failed or are intolerant to one or more monoclonal antibodies. [ Time Frame: 70 weeks ]
    Number of subjects who tolerate intravenous ExoFlo in those subjects with moderately to severely active Ulcerative colitis who have failed or are intolerant to one or more monoclonal antibodies.

  2. Number of adverse events in subjects who received intravenous ExoFlo in those subjects with moderately to severely active Ulcerative colitis who have failed or are intolerant to one or more monoclonal antibodies. [ Time Frame: 70 weeks ]
    Number of adverse events in subjects who received intravenous ExoFlo in those subjects with moderately to severely active Ulcerative colitis who have failed or are intolerant to one or more monoclonal antibodies.


Secondary Outcome Measures :
  1. Number of subjects with improvement with intravenous ExoFlo in inducing clinical remission in those subjects with moderately to severely active Ulcerative colitis who have failed or are intolerant to one or more monoclonal antibodies. [ Time Frame: 70 weeks ]
    Number of subjects with improvement with intravenous ExoFlo in inducing clinical remission in those subjects with moderately to severely active Ulcerative colitis who have failed or are intolerant to one or more monoclonal antibodies.

  2. Number of subjects with improvement with intravenous ExoFlo in inducing clinical response in those subjects with moderately to severely active Ulcerative colitis who have failed or are intolerant to one or more monoclonal antibodies. [ Time Frame: 70 weeks ]
    Number of subjects with improvement with intravenous ExoFlo in inducing clinical response in those subjects with moderately to severely active Ulcerative colitis who have failed or are intolerant to one or more monoclonal antibodies.

  3. Number of subjects with improving disease-specific health-related quality of life after receiving intravenous ExoFlo. [ Time Frame: 70 Weeks ]
    Number of subjects with improving disease-specific health-related quality of life after receiving intravenous ExoFlo.

  4. Measurement of subject's C-reactive protein (CRP) [ Time Frame: 70 Weeks ]
    Measurement of subject's C-reactive protein (CRP)

  5. Measurement of subject fecal calprotectin [ Time Frame: 70 weeks ]
    Measurement of subject fecal calprotectin

  6. Measurement of subject fecal lactoferrin [ Time Frame: 70 weeks ]
    Measurement of subject fecal lactoferrin



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and Females 18-75 years of age
  • Ulcerative colitis of at least 6 months duration with medically refractory symptoms
  • Failed to have improvement of disease while receiving at least one monoclonal antibody (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab) or tofacitinib for 8 weeks duration prior to enrollment.
  • Or has a contra-indication to monoclonal antibodies
  • 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.
  • If AZA, 6-MP, or MTX has been recently discontinued, it must have been stopped for atleast 4 weeks.
  • 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 equivalentand must have been stable for at least 4 weeks.
  • If receiving budesonide, the dose must have been stable for at least 2 weeks.
  • If oral 5-ASA compounds or oral corticosteroids (including budesonide) have been recently discontinued, they must have been stopped for at least 2 weeks.
  • 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.
  • 6-thioguanine (6-TG) must have been discontinued for at least 4 weeks.
  • Rectal corticosteroids (ie, 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 (ie, 5-ASAs administered to the rectum or sigmoid colon viafoam or enema or suppository) for at least 2 weeks.
  • Parenteral corticosteroids for at least 2 weeks.
  • Total parenteral nutrition (TPN) for at least 2 weeks.
  • Antibiotics for the treatment of UC (eg, ciprofloxacin, metronidazole, or rifaximin) for atleast 2 weeks.
  • No colonic dysplasia and malignancy as ruled out by colonoscopy within 30 days of MSC delivery
  • Ability to comply with protocol
  • Competent and able to provide written informed consent
  • Stated willingness to comply with all study procedures and availability for the duration of the study
  • If patient is of reproductive capacity, willing to use adequate birth control measures while they are in the study

Exclusion Criteria:

  • 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
  • eGRF < 60
  • HbA1C > 8%
  • Subjects with abnormal coagulation studies:
  • Prothrombin time (PT) > 1.5 times the upper limits of normal
  • Partial thromboplastin time (PTT) > 1.5 times the upper limits of normal
  • International normalized ratio (INR) > 1.5 times the upper limits of normal
  • 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.
  • Subjects with abnormal vital signs as defined by any of the following:
  • Systolic blood pressure >160 or <90 mmHg
  • Diastolic blood pressure >90 or <60 mmHg
  • Pulse <60 or >105 bpm
  • Respiratory Rate <9 and >25 breaths per minute
  • Temperature: >100.4 degrees Fahrenheit
  • SpO2 : <92%
  • History of cancer including melanoma (with the exception of localized skin cancers) within 5 years of study enrollment
  • Investigational drug within one year of study enrollment
  • Pregnant or breast feeding.
  • If patient is of reproductive capacity, unwilling to use adequate birth control measures while they are in the study
  • Fulminant colitis requiring emergency surgery
  • Concurrent active clostridium difficile infection of the colon
  • Concurrent CMV infection of the colon
  • Evidence of colonic perforation
  • Massive hemorrhage from the colon requiring emergent surgery
  • Crohn's colitis or indeterminate colitis
  • Microscopic, ischemic or infectious colitis
  • Neoplasia of the colon and preoperative biopsy
  • Presence of an ostomy
  • Prior small bowel resection
  • Previous colonic resection
  • Colonic stricture that unable to pass an adult colonoscope
  • Active or latent tuberculosis
  • Unable to wean off corticosteroids
  • Patients with extra colonic ulcerative colitis including primary sclerosing cholangitis
  • 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
  • Patients with known allergy to local anesthetics
  • Patients taking anticoagulant medications (e.g. warfarin, heparin) or clopidogrel (Plavix) to reduce the risk of bleeding/ hemarthrosis
  • Individuals with inherited or acquired hypercoagulable states, history of thromboembolic events or bleeding disorders
  • Electrocardiogram demonstrating cardiac arrhythmia, except for sinus tachycardia within the predefined limit of no greater than 105 bpm.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05176366


Contacts
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Contact: Heidi Moran 800-791-1021 hmoran@directbioloics.com

Sponsors and Collaborators
Direct Biologics, LLC
Investigators
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Principal Investigator: Vikram Sengupta, MD Direct Biologics
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Responsible Party: Direct Biologics, LLC
ClinicalTrials.gov Identifier: NCT05176366    
Other Study ID Numbers: DB-EF-ULCERATIVE-0004
First Posted: January 4, 2022    Key Record Dates
Last Update Posted: January 5, 2022
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Direct Biologics, LLC:
EXOFLO
ULCERATIVE COLITIS
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases