What side effects are associated with this type of intervention?

Common treatments for Ulcerative Colitis include mesalamine, sulfasalazine, corticosteroids, and biologics such as anti-TNF agents. Mesalamine and sulfasalazine can cause nausea, headache, fever, rash, pancreatitis, and pneumonitis. Corticosteroids are associated with systemic side effects like adrenal suppression, osteoporosis, and increased infection risk. Anti-TNF agents may lead to infections, infusion reactions, and potential malignancy risks. Mesenchymal stem cell treatments, including extracellular vesicles, are still under investigation, but potential side effects may include infection, immune reactions, and local site reactions.

What prior FDA approvals exist?

The FDA has approved several treatments for Ulcerative Colitis, including biologics like infliximab, adalimumab, and vedolizumab, which target specific components of the immune system to reduce inflammation. While mesenchymal stem cell-derived therapies like ExoFlo are still under investigation, the FDA has shown interest in innovative treatments, including stem cell-based therapies, for various conditions. These approvals reflect a broader trend towards personalized and advanced therapeutic options in managing inflammatory bowel diseases.

What other types of research exist?

Promising novel alternatives to ExoFlo for Ulcerative Colitis patients include: 1) Ustekinumab, a monoclonal antibody targeting interleukin-12 and interleukin-23, which has shown efficacy in treating immune-mediated disorders. 2) Vedolizumab, an integrin receptor antagonist that has demonstrated benefits in patients with UC. 3) Risankizumab, another monoclonal antibody targeting interleukin-23, which has shown positive results in recent clinical trials for Crohn's disease and may be applicable to UC. These therapies offer targeted mechanisms of action and have been supported by clinical evidence for their effectiveness in managing UC.

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Mesenchymal Stem Cell Therapy

ExoFlo for Ulcerative Colitis

Phase 1

Waitlist Available

Led By Vikram Sengupta, MD

Research Sponsored by Direct Biologics, LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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 via foam 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

Ulcerative colitis of at least 6 months duration with medically refractory symptoms

Must not have

Fulminant colitis requiring emergency surgery

Patients taking anticoagulant medications (e.g. warfarin, heparin) or clopidogrel (Plavix) to reduce the risk of bleeding/ hemarthrosis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up week 6 and week 46

Awards & highlights

No Placebo-Only Group

Summary

This trial tests ExoFlo, a bone marrow cell-derived treatment, on patients with severe ulcerative colitis who haven't responded to other treatments. ExoFlo aims to reduce inflammation and heal the gut.

Who is the study for?

Adults aged 18-75 with medically refractory ulcerative colitis can join this trial. They must have tried certain medications without improvement and be on stable doses of others if used. Participants need to use birth control if applicable, not have colon cancer or dysplasia, and cannot be pregnant or breastfeeding.

What is being tested?

The trial is testing ExoFlo, a mesenchymal stem cell-derived product for treating ulcerative colitis that hasn't responded to standard treatments. It's an open-label Phase I study conducted at multiple sites over approximately 58 weeks per participant.

What are the potential side effects?

As this is a Phase I trial primarily assessing safety, specific side effects are not listed but may include typical reactions related to immune modulation such as infusion-related reactions, potential allergic responses, or other unforeseen complications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have had ulcerative colitis for over 6 months and my symptoms haven't improved with treatment.

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I didn't improve after 8 weeks on specific drugs or can't take them due to side effects or health reasons.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I needed emergency surgery for severe colitis.

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I am on blood thinners like warfarin or clopidogrel.

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I have ulcerative colitis that affects more than just my colon.

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I have a colon tumor and had a biopsy before surgery.

Select...

I had emergency surgery for severe bleeding in my colon within the last 6 months.

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I am unable to understand and give consent for treatment.

Select...

I have a confirmed diagnosis of HIV, Hepatitis B, or Hepatitis C.

Select...

I have been diagnosed with a type of colitis.

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I have tuberculosis, whether active or not.

Select...

I currently have an active C. difficile infection in my colon.

Select...

I have had part of my colon surgically removed.

Select...

I cannot stop taking corticosteroids.

Select...

I have a known blood clotting disorder.

Select...

I have Crohn's colitis or indeterminate colitis.

Select...

I have had surgery to remove part of my small intestine.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ week 6 and week 46

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~week 6 and week 46

This trial's timeline: 3 weeks for screening, Varies for treatment, and week 6 and week 46 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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.

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 study objectives

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

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

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

+1 more

Side effects data

From 2021 Phase 2 trial • 102 Patients • NCT04493242

35%

Acute Respiratory Failure

26%

Anxiety

24%

Hypotension

24%

Hypokalaemia

15%

Respiratory Failure

12%

Cardiac Arrest

12%

Hyperkalaemia

Anaemia

Leukocytosis

Hyperglycaemia

Constipation

Pyrexia

Agitation

Pneumonia

Embolism

Hypertension

Multiple Organ Dysfunction Syndrome

Sepsis

Hypoalbuminaemia

Thrombocytopenia

Atrial Fibrillation

Type 2 Diabetes Mellitus

Fluid Overload

Hypophosphataemia

Upper Respiratory Tract Infection

Myalgia

Confusional State

Acute Kidney Injury

Hypothermia

Septic Shock

Dyspepsia

Cough

Nasal Congestion

Rales

Fungal Skin Infection

Bradycardia

Pancreatitis

Musculoskeletal Chest Pain

Encephalopathy

Renal Ischemia

Renal Tubular Necrosis

Pneumothorax

Atrial Flutter

Myocardial Ischaemia

Tachycardia

Blood Glucose Increased

Diabetes Mellitus

Abdominal Pain

Diarrhoea

Nausea

Oropharyngeal Pain

Pharyngeal Haemorrhage

Fall

Hypocalcaemia

Oedema Peripheral

Fungaemia

Wound Infection

Hypernatraemia

Hyperphosphataemia

Malnutrition

Syncope

Acidosis

Troponin I Increased

Dehydration

Epistaxis

Enterococcal Infection

100%

80%

60%

40%

20%

Study treatment Arm

Experimental Dose 1

Placebo

Experimental Dose 2

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: 15ml at Day 0, 2, 4, 30 ml at Week 2, Week 6, and every 4 weeks after to week 46Experimental Treatment1 Intervention

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).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

ExoFlo

2020

Completed Phase 2

~110

0 / 18Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Ulcerative Colitis (UC) include mesalamine, corticosteroids, immunomodulators, and biologics. Mesalamine works by reducing inflammation directly in the colon lining. Corticosteroids suppress the overall immune response to decrease inflammation. Immunomodulators like azathioprine alter the immune system to prevent it from attacking the colon. Biologics, such as anti-TNF agents, target specific proteins involved in the inflammatory process. Emerging treatments like mesenchymal stem cell-derived extracellular vesicles (similar to ExoFlo) offer a novel approach by potentially modulating the immune response and promoting tissue repair. These mechanisms are crucial for UC patients as they aim to reduce inflammation, promote healing, and maintain remission, thereby improving quality of life.

Emerging Therapies for Inflammatory Bowel Diseases.