Ulcerative ColitisPhase 1NCT05176366
Study of ExoFlo for the Treatment of Medically Refractory Ulcerative Colitis
A Phase 1 study testing ExoFlo in people with Ulcerative Colitis and Inflammatory Bowel Diseases, run by Direct Biologics, LLC at 2 sites in United States.
Trial 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 ulcerative colitis. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Ulcerative Colitis, Inflammatory Bowel Diseases
- What is being tested?
- ExoFlo
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 2 sitesUnited States
- Study dates
- 19 Dec 2022to 1 Dec 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 is intolerant 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 be on a stable dose for at least 4 weeks prior to receiving the first dose of the study drug.
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- 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 the study drug.
- If receiving oral 5-ASA compounds, the dose must have been stable for at least 4 weeks prior to receiving the first dose of the study drug.
- 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 the study drug.
- If receiving budesonide, the dose must have been stable for at least 2 weeks prior to receiving the first dose of the 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 the 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.
- 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 at least 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
Who cannot join
- 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
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- 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
- 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 prior to first ExoFlo delivery 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 via colonic biopsy with CMV stain taken within 90 days
- Evidence of colonic perforation
- Massive hemorrhage from the colon requiring emergent surgery in the 6 months prior to screening.
- 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 previously diagnosed, known inherited or acquired hypercoagulable states
- Electrocardiogram demonstrating cardiac arrhythmia, except for sinus tachycardia within the predefined limit of no greater than 105 bpm.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Direct Biologics Investigational Site
Los Angeles, California, 90048
Direct Biologics Investigational Site
New York, New York, 10016
About this study
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
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 ulcerative colitis.
- Short Title: ExoFlo for ulcerative colitis
- Phase: 1
- Methodology: Open label
- Study Duration: 24 months
- Subject Participation: 58 weeks
- Single or Multi-Site: Multi-Site
Read the detailed description
Primary Objectives:
- To evaluate the feasibility of intravenous ExoFlo in subjects with medically refractory ulcerative colitis who have failed, or are intolerant, or have a contraindication to one or more monoclonal antibodies.
- To evaluate the safety of intravenous ExoFlo in subjects with medically refractory ulcerative colitis who have failed, or are intolerant, or have a contraindication to one or more monoclonal antibodies.
Secondary Objectives:
- To evaluate the efficacy of intravenous ExoFlo in inducing clinical remission in subjects with medically refractory ulcerative colitis who have failed, or are intolerant, or have a contraindication to one or more monoclonal antibodies.
- To evaluate the efficacy of intravenous ExoFlo in inducing clinical response in subjects with medically refractory ulcerative colitis who have failed, or are intolerant, or have a contraindication 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) and fecal calprotectin.
Number of Subjects: 10
Diagnosis and Main Inclusion Criteria: Subjects must have medically refractory ulcerative colitis and have no prior intestinal surgery for ulcerative colitis.
Study Product, Dose, Route, Regimen:
IV administration of 15 mL of 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 (n=10), (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.
- Conditions
- Ulcerative Colitis, Inflammatory Bowel Diseases
- Being tested
- ExoFlo
- Keywords
- ExoFlo, Ulcerative Colitis, Extracellular Vesicle, Inflammatory Bowel Diseases
- Medical subject headings
- Colitis, Ulcerative, Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExoFloBiological
Intravenous administration of bone marrow mesenchymal stem cell derived extracellular vesicles
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Biological: ExoFlo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of intravenous ExoFlo in subjects with medically refractory ulcerative colitis 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.
Measured: 58 Weeks
Feasibility of intravenous ExoFlo in subjects with medically refractory ulcerative colitis 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.
Measured: 58 Weeks
Secondary outcomes (4)
To evaluate the efficacy of intravenous ExoFlo in inducing clinical remission or response at week 6 and week 46.
Efficacy will be evaluated as:
- Clinical remission: Mayo Score of less than or equal to 2 with no individual sub score greater than 1.
- Clinical response: Reduction in Mayo Score of greater than or equal to 3 points and greater than or equal to 30 percent from baseline with an accompanying decrease in rectal bleeding sub score of greater than or equal to 1 point or absolute rectal bleeding sub score of less than or equal to 1 point.
Measured: Week 6 and Week 46
To evaluate the efficacy of intravenous ExoFlo in improving disease-specific health related quality of life.
Efficacy will be evaluated as:
- Improvement on the 36 Item Short Form Health Survey (SF-36)
- Improvement on the EuroQol 5 Dimensions Survey (EQ-5D)
Measured: 58 Weeks
To evaluate the pharmacokinetics and pharmacodynamics of ExoFlo therapy, including changes in C-reactive protein (CRP) and fecal calprotectin.
Evaluated as:
Measuring changes in C-reactive protein (CRP) and fecal calprotectin.
Measured: 58 Weeks
To evaluate treatment failure as defined by disease worsening, need for rescue medications or surgical intervention for treatment of UC, or study drug-related adverse event leading to discontinuation from the study.
Evaluated as:
Number of subjects with disease worsening, needing rescue medications or surgical intervention for treatment of UC, or study drug-related adverse events leading to discontinuation of study.
Measured: 58 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2022
- Study start19 Dec 2022
- Primary completion1 Dec 2024
- Study completion1 Dec 2024
Why it stopped: Enrollment challenges.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Direct Biologics, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bill Arana, Study director, Direct Biologics, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05176366
- Sponsor's protocol ID
- DB-EF-UC-01
- Status last verified
- Feb 2025
- First submitted
- 17 Nov 2021
- Last updated
- 11 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05176366
- Acronym / sponsor ID
- DB-EF-UC-01
- Conditions
- Ulcerative Colitis, Inflammatory Bowel Diseases
- Keywords
- ExoFlo, Ulcerative Colitis, Extracellular Vesicle, Inflammatory Bowel Diseases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Enrollment challenges.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Direct Biologics, LLCIndustry (pharma, biotech, devices)
- Study start
- 19 Dec 2022 (actual)
- Primary completion
- 1 Dec 2024 (actual)
- Study completion
- 1 Dec 2024 (actual)
- First posted
- 4 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 ulcerative colitis.
- Short Title: ExoFlo for ulcerative colitis
- Phase: 1
- Methodology: Open label
- Study Duration: 24 months
- Subject Participation: 58 weeks
- Single or Multi-Site: Multi-Site
Detailed description
Primary Objectives:
- To evaluate the feasibility of intravenous ExoFlo in subjects with medically refractory ulcerative colitis who have failed, or are intolerant, or have a contraindication to one or more monoclonal antibodies.
- To evaluate the safety of intravenous ExoFlo in subjects with medically refractory ulcerative colitis who have failed, or are intolerant, or have a contraindication to one or more monoclonal antibodies.
Secondary Objectives:
- To evaluate the efficacy of intravenous ExoFlo in inducing clinical remission in subjects with medically refractory ulcerative colitis who have failed, or are intolerant, or have a contraindication to one or more monoclonal antibodies.
- To evaluate the efficacy of intravenous ExoFlo in inducing clinical response in subjects with medically refractory ulcerative colitis who have failed, or are intolerant, or have a contraindication 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) and fecal calprotectin.
Number of Subjects: 10
Diagnosis and Main Inclusion Criteria: Subjects must have medically refractory ulcerative colitis and have no prior intestinal surgery for ulcerative colitis.
Study Product, Dose, Route, Regimen:
IV administration of 15 mL of 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 (n=10), (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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 15ml at Day 0, 2, 4, 30 ml at Week 2, Week 6, and every 4 weeks after to week 46 | Experimental | Biological: ExoFloIV 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). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Males and Females 18-75 years of age
- Ulcerative colitis of at least 6 months duration with medically refractory symptoms
- 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.
- The following medications/therapies must have been discontinued before first administration of study agent:
- No colonic dysplasia and malignancy as ruled out by colonoscopy within 30 days of MSC delivery
Key exclusion criteria (47 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ExoFloIntravenous administration of bone marrow mesenchymal stem cell derived extracellular vesicles | Biological | 15ml at Day 0, 2, 4, 30 ml at Week 2, Week 6, and every 4 weeks after to week 46 |
Primary outcome
Safety of intravenous ExoFlo in subjects with medically refractory ulcerative colitis who have failed, or are intolerant, or have a contraindication to one or more monoclonal antibodies.
Time frame: 58 Weeks
Safety will be defined as lack of serious adverse events or adverse advents related to treatment with the study therapeutic.
Feasibility of intravenous ExoFlo in subjects with medically refractory ulcerative colitis who have failed, or are intolerant, or have a contraindication to one or more monoclonal antibodies.
Time frame: 58 Weeks
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.
4 secondary outcomes
To evaluate the efficacy of intravenous ExoFlo in inducing clinical remission or response at week 6 and week 46.
Time frame: Week 6 and Week 46
To evaluate the efficacy of intravenous ExoFlo in improving disease-specific health related quality of life.
Time frame: 58 Weeks
To evaluate the pharmacokinetics and pharmacodynamics of ExoFlo therapy, including changes in C-reactive protein (CRP) and fecal calprotectin.
Time frame: 58 Weeks
To evaluate treatment failure as defined by disease worsening, need for rescue medications or surgical intervention for treatment of UC, or study drug-related adverse event leading to discontinuation from the study.
Time frame: 58 Weeks
Results and safety
The study was stopped early (reason given: Enrollment challenges.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2025.
- Direct Biologics, LLCLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bill Arana study director
Direct Biologics, LLC
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ExoFlo in people with Ulcerative Colitis and Inflammatory Bowel Diseases, run by Direct Biologics, LLC at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 47 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Enrollment challenges.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of intravenous ExoFlo in subjects with medically refractory ulcerative colitis who have failed, or are intolerant, or have a contraindication to one or more monoclonal antibodies. (time frame: 58 Weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2025.