Overview
Study of ExoFlo for the Treatment of Medically Refractory Ulcerative Colitis
Status:
Not yet recruiting
Not yet recruiting
Trial end date:
2024-03-01
2024-03-01
Target enrollment:
0
0
Participant gender:
All
All
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 colitisPhase:
Phase 1Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Direct Biologics, LLC
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.