Colitis, Ulcerative
Conditions
Keywords
Ulcerative colitis (UC), Inflammatory Bowel Disease (IBD), Trichuris suis ova (TSO)
Brief summary
The purpose of this study is to evaluate the safety and effectiveness of trichuris suis ova (TSO) in ulcerative colitis (UC). We will look at how TSO affects the body's immune response and if there are related changes in participants' UC.
Detailed description
The cause of UC, an inflammatory bowel disease (IBD), is not well understood. It is believed to be caused from an abnormal immune response to the normal bacteria that live in the gut (intestines and colon). This response acts as an attack on the healthy tissue of the bowel by a person's own immune cells which leads to disease. It is well known that autoimmune diseases such as IBD, asthma, diabetes, and multiple sclerosis are more common in industrialized, well-developed countries with better sanitation and hygiene, as in the United States. These cleaner environments reduce exposure to germs and parasites naturally found in the environment. This reduced exposure may trigger responses in the body that make people more prone to diseases such as UC. People in non-industrialized countries and the tropics, where parasites are common, rarely develop these diseases. This observation has led researchers to want to better understand the relationship between the lack of natural bacteria in the gut and the onset of autoimmune diseases like as UC.
Interventions
BIOLOGICALTrichuris suis ova (TSO)
Six doses of TSO orally over a ten-week period (e.g., every 2 weeks x 10 weeks for a total of 6 total doses)
BIOLOGICALPlacebo
Six doses of TSO placebo orally over a ten-week period (e.g., every 2 weeks x 10 weeks for a total of 6 total doses)
Sponsors
Coronado Biosciences, Inc.
Autoimmunity Centers of Excellence
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Subject has provided written informed consent 2. Diagnosis of UC (newly diagnosed or established patients) as determined by medical history, endoscopic and histological confirmation with the proximal disease extent limited to the left colon (distal to the splenic flexure), and accessible by flexible sigmoidoscopy. Patients with left-sided disease and the presence of a periappendiceal red patch (limited cecal inflammation) will be eligible as long as there is no intervening evidence of colitis between the cecal base and the upper boundary of inflammation in the left colon. 3. Mayo score \>/= 4, as scored at Screen 2 4. If taking the following medications at Screen 1, subjects must meet the following criteria: 1. Oral Corticosteroids: stable treatment for at least 4 weeks prior to Day 0 with a maximum dose equivalent to \<\\=15 mg/day of prednisone 2. Immunosuppressants (azathioprine (AZA) or 6-mercaptopurine (6-MP)): treatment for at least 12 weeks with a stable dose, not exceeding 2.5 mg/kg/day of AZA or 1.5 mg/kg/day of 6-MP, during the 4 weeks prior to Day 0 3. Aminosalicylates: stable oral doses up to 4.8 g/day for at least 4 weeks prior to Day 0.
Exclusion criteria
1. Subjects whose UC is anticipated to require surgical, endoscopic, or radiologic intervention during study participation 2. Uncontrolled GI bleeding 3. Subjects who have disease limited to the rectum (maximum disease extent of less than 15 cm) 4. Women who are pregnant, breast-feeding, or planning to become pregnant during the study. All women of childbearing potential must have a negative serum pregnancy test at Screen 2 prior to randomization of treatment. 5. Women of childbearing potential not using adequate birth control measures (e.g., total abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, surgical sterilization, Depo-Provera, or hormonal implants). 6. Current or recent serious systemic disorder including clinically significant impairment in cardiac, pulmonary, liver, renal, endocrine, hematologic, or neurologic function, based on investigator discretion 7. Subjects currently receiving the following concomitant medications: 1. Prednisone or its equivalent at unstable doses or at doses exceeding 15 mg/day within 4 weeks prior to Day 0 2. Local steroids such as budesonide, Colifoam, or Predsol enemas within 2 weeks prior to Screen 2 3. Topical therapies, either mesalamine or steroids, taken within 2 weeks of Screen 2 4. Non-steroidal anti-inflammatory drugs (NSAIDs), Cyclooxygenase (COX)-2 inhibitors, or aspirin \>100 mg/day within 2 weeks prior to Screen 2 5. Tumor necrosis factor (TNF)-alpha inhibitors including but not limited to infliximab (Remicade) or adalimumab (Humira) within 12 weeks of Day 0 6. Any biological agent within 12 weeks of Day 0 7. Metronidazole within 4 weeks of Day 0 8. Receipt of any investigational agent within the 12 weeks prior to Day 0 9. Antibacterial or oral antifungal agents within 4 weeks of Screen 2 10. Interferon (IFN) therapy 11. Anticoagulants 12. Methotrexate 8. Blood transfusion within the 12 weeks prior to Day 0 9. Presence of any of the following abnormal laboratory parameters at Screen 1: 1. Hemoglobin \< 10.0 g/dL 2. White Blood Count (WBC) \< 4,000 or \> 20,000/L (equivalent to WBC \< 4 or \> 20 x109/L) 3. Platelets \< 100,000 or \> 800,000/L (equivalent to platelets \< 100 or \> 800 x109/L) 4. Total bilirubin \> 1.5 × Upper limit of normal (ULN) 5. Alanine transaminase (ALT) \> 2 × ULN 6. Aspartate transaminase (AST) \> 2 × ULN 7. Alkaline phosphatase (ALK) \> 1.5 × ULN 8. Gamma-glutamyl transferase (GGT) \> 1.5 × ULN 9. Creatinine \> 1.5 × ULN 10. History of drug or alcohol abuse within one year prior to Day 0 11. Inability to understand the nature and requirements of the study, or to comply with the study procedures or planned schedule of study visits 12. Evidence of infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C 13. Active infection with C. difficile, bacterial enteric pathogens, or pathogenic ova/parasites 14. History of malignancy within the last 5 years, except for resected basal or squamous cell carcinoma, treated cervical dysplasia, or treated in situ cervical cancer Grade I 15. History of colonic dysplasia 16. Any social or medical condition that, in the opinion of the investigator, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved a Clinical Response at Week 12 | Week 12 | Clinical response is defined as a reduction in the Mayo score of at least 3 points and at least a 30% reduction from Baseline, along with either a decrease from Baseline in the rectal bleeding subscore of more than 1 point or a rectal bleeding subscore of 0 or 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With Healed Colonic Mucosa at Week 12 | Week 12 | Healed colonic mucosa is defined as a Mayo endoscopy score of 0 or 1. |
| Percent of Participants With a Modified Clinical Response | From Day 0 through time of first clinical response or end of follow-up, whichever comes first, up to 12 Weeks | Modified clinical response is defined as a reduction in the modified Mayo score (i.e., minus the endoscopy component) of at least 2 points from baseline. |
| Time to Modified Clinical Response | From Baseline through the day that modified clinical response is reached. Week 16 is the last visit that the modified Mayo score is assessed. | Number of days to reach a modified clinical response. Modified clinical response is defined as a reduction in the modified Mayo score (i.e., minus the endoscopy component) of at least 2 points from baseline. |
| Percent of Participants Who Achieved Remission at Week 12 | Week 12 | Remission is defined as a Mayo score of less than or equal to 1 with absence of rectal bleeding and endoscopy score of 0 or 1. |
| Percent of Participants With Increase in Diarrhea | From Day 0 through end of follow-up, up to 36 weeks | An increase in diarrhea is defined as an increase in the Mayo Score's Stool Frequency score by at least 1 point from baseline at any time during follow-up. |
| Percent of Participants With Increase in Concurrent Ulcerative Colitis (UC) Medications or New Rescue Medications Added | From Day 0 through Week 16 | New or increase in UC medications is defined as a need for dose-escalation of concurrent medications or need for rescue medications to treat UC through Week 16. |
| Percent of Participants With Colonoscopic Evidence of Visible Worm | From Day 0 through end of follow-up, up to 36 weeks | Stool evaluations for ova and parasites confirmed the absence of T. suis. If evidence suggested a presence of T. suis, a colonoscopy would be performed to confirm invasion with a visible worm. |
Countries
United States
Participant flow
Recruitment details
Of all the participating sites, nine reached the study intervention randomization phase for \>=one participant.The first site was activated in November 2013 and the last participant was randomized in March 2015.
Participants by arm
| Arm | Count |
|---|---|
| TSO 7500 Participants were randomized to receive six doses of 7500 viable, embryonated Trichuris suis ova (TSO) in liquid suspension orally over a 10-week period. | 9 |
| Placebo Participants were randomized to receive six doses of placebo in liquid suspension orally over a 10-week period. | 7 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Decision of Sponsor | 0 | 1 |
| Overall Study | Disease Exacerbation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo | TSO 7500 |
|---|---|---|---|
| Age, Continuous | 42.1 years STANDARD_DEVIATION 10 | 44.7 years STANDARD_DEVIATION 11.4 | 40.0 years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 6 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Mayo Score for Assessment of Ulcerative Colitis Activity | 8.3 Total Mayo Score STANDARD_DEVIATION 1.5 | 7.4 Total Mayo Score STANDARD_DEVIATION 1.3 | 9.0 Total Mayo Score STANDARD_DEVIATION 1.2 |
| Percentage of Participants at Baseline Who Were Taking a Corticosteroid | 25.0 percentage of participants | 14.3 percentage of participants | 33.3 percentage of participants |
| Percentage of Participants at Baseline Who Were Taking Thiopurine | 6.3 percentage of participants | 0.0 percentage of participants | 11.1 percentage of participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 7 Participants | 7 Participants |
| Region of Enrollment United States | 16 participants | 7 participants | 9 participants |
| Sex: Female, Male Female | 6 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 10 Participants | 5 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 8 | 4 / 7 |
| serious Total, serious adverse events | 0 / 8 | 0 / 7 |
Outcome results
Primary
Percentage of Participants Who Achieved a Clinical Response at Week 12
Clinical response is defined as a reduction in the Mayo score of at least 3 points and at least a 30% reduction from Baseline, along with either a decrease from Baseline in the rectal bleeding subscore of more than 1 point or a rectal bleeding subscore of 0 or 1.
Time frame: Week 12
Population: The Modified Intent-to-Treat (mITT) population included all randomized subjects who received at least one dose of either TSO or placebo. Only mITT subjects with clinical response results at Week 12 are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TSO 7500 | Percentage of Participants Who Achieved a Clinical Response at Week 12 | 57.1 percentage of participants |
| Placebo | Percentage of Participants Who Achieved a Clinical Response at Week 12 | 50.0 percentage of participants |
p-value: 1Fisher Exact
Secondary
Percent of Participants Who Achieved Remission at Week 12
Remission is defined as a Mayo score of less than or equal to 1 with absence of rectal bleeding and endoscopy score of 0 or 1.
Time frame: Week 12
Population: The Modified Intent-to-Treat (mITT) population included all randomized subjects who received at least one dose of either TSO or placebo. Only mITT subjects with remission results at Week 12 are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TSO 7500 | Percent of Participants Who Achieved Remission at Week 12 | 14.3 percentage of participants |
| Placebo | Percent of Participants Who Achieved Remission at Week 12 | 16.7 percentage of participants |
p-value: 1Fisher Exact
Secondary
Percent of Participants With a Modified Clinical Response
Modified clinical response is defined as a reduction in the modified Mayo score (i.e., minus the endoscopy component) of at least 2 points from baseline.
Time frame: From Day 0 through time of first clinical response or end of follow-up, whichever comes first, up to 12 Weeks
Population: The Modified Intent-to-Treat (mITT) population included all randomized subjects who received at least one dose of either TSO or placebo. Only mITT subjects with baseline and at least one post-baseline modified clinical response result are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TSO 7500 | Percent of Participants With a Modified Clinical Response | 88.9 percentage of participants |
| Placebo | Percent of Participants With a Modified Clinical Response | 71.4 percentage of participants |
p-value: 0.55Fisher Exact
Secondary
Percent of Participants With Colonoscopic Evidence of Visible Worm
Stool evaluations for ova and parasites confirmed the absence of T. suis. If evidence suggested a presence of T. suis, a colonoscopy would be performed to confirm invasion with a visible worm.
Time frame: From Day 0 through end of follow-up, up to 36 weeks
Population: The Safety population included all subjects for whom study treatment was initiated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TSO 7500 | Percent of Participants With Colonoscopic Evidence of Visible Worm | 0 percentage of participants |
| Placebo | Percent of Participants With Colonoscopic Evidence of Visible Worm | 0 percentage of participants |
Secondary
Percent of Participants With Healed Colonic Mucosa at Week 12
Healed colonic mucosa is defined as a Mayo endoscopy score of 0 or 1.
Time frame: Week 12
Population: The Modified Intent-to-Treat (mITT) population included all randomized subjects who received at least one dose of either TSO or placebo. Only mITT subjects with a Mayo endoscopy score at Week 12 are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TSO 7500 | Percent of Participants With Healed Colonic Mucosa at Week 12 | 66.7 percentage of participants |
| Placebo | Percent of Participants With Healed Colonic Mucosa at Week 12 | 16.7 percentage of participants |
p-value: 0.242Fisher Exact
Secondary
Percent of Participants With Increase in Concurrent Ulcerative Colitis (UC) Medications or New Rescue Medications Added
New or increase in UC medications is defined as a need for dose-escalation of concurrent medications or need for rescue medications to treat UC through Week 16.
Time frame: From Day 0 through Week 16
Population: The Safety population included all subjects for whom study treatment was initiated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TSO 7500 | Percent of Participants With Increase in Concurrent Ulcerative Colitis (UC) Medications or New Rescue Medications Added | 44.4 percentage of participants |
| Placebo | Percent of Participants With Increase in Concurrent Ulcerative Colitis (UC) Medications or New Rescue Medications Added | 28.6 percentage of participants |
p-value: 0.633Fisher Exact
Secondary
Percent of Participants With Increase in Diarrhea
An increase in diarrhea is defined as an increase in the Mayo Score's Stool Frequency score by at least 1 point from baseline at any time during follow-up.
Time frame: From Day 0 through end of follow-up, up to 36 weeks
Population: The Safety population included all subjects for whom study treatment was initiated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TSO 7500 | Percent of Participants With Increase in Diarrhea | 11.1 percentage of participants |
| Placebo | Percent of Participants With Increase in Diarrhea | 28.6 percentage of participants |
p-value: 0.55Fisher Exact
Secondary
Time to Modified Clinical Response
Number of days to reach a modified clinical response. Modified clinical response is defined as a reduction in the modified Mayo score (i.e., minus the endoscopy component) of at least 2 points from baseline.
Time frame: From Baseline through the day that modified clinical response is reached. Week 16 is the last visit that the modified Mayo score is assessed.
Population: The Modified Intent-to-Treat (mITT) population included all randomized subjects who received at least one dose of either TSO or placebo. Only mITT subjects who achieved a modified clinical response are included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TSO 7500 | Time to Modified Clinical Response | 34.5 Days |
| Placebo | Time to Modified Clinical Response | 28.0 Days |