Crohn's Disease
Conditions
Keywords
T. suis ova, Crohn's disease
Brief summary
This is a sequential dose-escalation (with up to 3 dose levels of TSO, ie, 500, 2500, and 7500 TSO), randomized (within each of 3 periods, with a ratio of 3:1 for TSO to placebo), double-blind, placebo-controlled study to evaluate the safety of a single dose of oral CNDO-201 Trichuris suis ova suspension, as compared to placebo, in patients with Crohn's Disease.
Interventions
BIOLOGICALTrichuris suis ova
single dose
OTHERPlacebo
Sponsors
Coronado Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Males or females, 18 to 55 years old. 2. Patient has confirmed diagnosis of Crohn's Disease by established criteria with a minimum disease duration of 3 months. 3. If patient is using concomitant medications, the dose/regimen is stable and remains stable for the two weeks of close observation following TSO administration. Concomitant medications may include: 1) Oral sulfasalazine, mesalazine (5-ASA), or mesalazine derivative, if receiving it for \>6 weeks and if receiving the same dose for at least 4 weeks; 2) Oral prednisone up to 15 mg/day, if receiving it for \>4 weeks and if receiving the same dose for at least 2 weeks; and 3) Azathioprine or 6-mercaptopurine if receiving it for \>3 months and if receiving the same dose for at least 8 weeks. 4. Hemoglobin ≥ 12 g/dL at screening. 5. Normal white blood cell count and normal lymphocyte count at screening. 6. Platelet count \> lower limit of normal at screening. 7. For females of childbearing potential, negative serum pregnancy test during the screening period, not breastfeeding for study duration, and willingness to use accepted forms of reliable birth control for study duration \[including bilateral tubal ligation, use of oral contraceptives, double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera®, hormonal implants, partner vasectomy, and total abstinence\]. Pregnancy tests are not required (indicate N/A) for males or females not of childbearing potential (post-menopausal with last menstrual period \>1 year ago or total hysterectomy). 8. Patient must have the ability to provide informed consent.
Exclusion criteria
1. Patient with ulcerative colitis, indeterminate colitis, or ulcerative proctitis. 2. Bowel surgery in past 6 months. 3. Resection of more than 50 cm of the ileum. 4. Ileostomy colostomy. 5. Septic complications. 6. Patient who is hospitalized or exhibiting signs of toxicity (sepsis), has significant or multiple strictures, or impending obstruction (as evidenced by abdominal distension, severe abdominal tenderness, fever, nausea, vomiting, or tachycardia) or anticipating a need for blood transfusion for gastrointestinal bleeding or in whom surgical intervention may be imminent. 7. Patient with gastrointestinal abscess, perforation, active draining fistulae or fistulae that are considered clinically significant or perianal lesions. 8. Patient with history of colorectal cancer or colorectal dysplasia. 9. Parenteral or tube feeding. 10. Patient with evidence of infectious colitis, e.g., Clostridium difficile, Amoebiasis, Giardia lamblia or stools positive for other enteric pathogens, ova or parasites at Screening. 11. Female patient who is pregnant or breastfeeding or wishing to become pregnant during study participation or unwilling to use birth control. 12. Patient with serum creatinine ≥ 2.0 mg/dL; blood urea nitrogen \>40 mg/dL; alkaline phosphatase \> 250 U/L; aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 100 U/L; or total bilirubin \>1.5 mg/dL. 13. Patient with white blood count \<5,000 or \>15,000/mm3; platelet count \<150,000 per μl; or iron or vitamin B12 deficiency. Correction of lab exclusion is allowed provided that medical condition is not deemed to put patient at risk and stability of result is sustained for a minimum of 30 days. 14. Patient with active hepatitis B virus, hepatitis C virus, liver cirrhosis or portal hypertension, cytomegalovirus, Epstein Barr Virus or herpes simplex virus or is known to be human immunodeficiency virus (HIV) positive. 15. Patient with primary sclerosing cholangitis. 16. Patient with active malignancy or treatment with anticancer drugs in the past 5 years. 17. Patient received cyclosporine, anti-TNF or other immunomodulatory agents other than azathioprine/6-mercaptopurine 12 weeks prior to Screening. 18. Patient received methotrexate 4 weeks prior to Screening. 19. Patient received metronidazole 2 weeks prior to Screening. 20. Patient received non-steroidal anti-inflammatory drugs (NSAIDS) within 2 weeks before Baseline visit for more than 3 consecutive days, except acetylsalicylic acid ≤ 350 mg/d which is allowed. 21. Patient received antibiotic, antifungal or antiparasitic medication in the last 2 weeks prior to Screening and/or would potentially require this during the study treatment period. 22. Patient with history of drug or alcohol abuse within 6 months prior to Screening. 23. Patient with evidence of poor compliance with medical advice and instruction including diet or medication. 24. Patient is unable or unwilling to swallow study medication suspension. 25. Patient with a significant medical condition which puts the patient at risk for study participation and/or for any reason is considered by the Investigator to be an unsuitable candidate to receive CNDO-201 TSO or is potentially put at risk by study procedures. 26. Patients who has participated in another clinical trial within 30 days of Screening for this trial and/or any experimental treatment for this population.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events | 6 mo | Comparison of safety and tolerability was performed across the dose levels by evaluating the post-dose tolerability of TSO in patients with Crohn's Disease via incidence of adverse events (i.e. # events) with a specific focus on reported gastrointestinal signs and symptoms |
Countries
United States
Participant flow
Recruitment details
A total of 8 clinical sites were initiated, all in the United States, with 6 of these sites enrolling at least one patient. Patients were enrolled from Nov, 2011 to Jan 30, 2012.
Pre-assignment details
All patients were immediately assigned to a treatment group upon enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo: single dose | 9 |
| TSO 500 Trichuris suis ova : single dose | 9 |
| TSO 2500 Trichuris suis ova : single dose | 9 |
| TSO 7500 Trichuris suis ova : single dose | 9 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | TSO 500 | TSO 2500 | Placebo | TSO 7500 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 9 Participants | 9 Participants | 9 Participants | 36 Participants |
| Age Continuous | 30.8 years STANDARD_DEVIATION 3.19 | 31.1 years STANDARD_DEVIATION 3.36 | 43.0 years STANDARD_DEVIATION 3.11 | 36.9 years STANDARD_DEVIATION 3.27 | 32.9 years STANDARD_DEVIATION 1.9 |
| Region of Enrollment United States | 9 participants | 9 participants | 9 participants | 9 participants | 36 participants |
| Sex: Female, Male Female | 6 Participants | 3 Participants | 4 Participants | 5 Participants | 18 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 5 Participants | 4 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 9 | 4 / 9 | 1 / 9 | 6 / 9 |
| serious Total, serious adverse events | 2 / 9 | 0 / 9 | 0 / 9 | 1 / 9 |
Outcome results
Primary
Incidence of Adverse Events
Comparison of safety and tolerability was performed across the dose levels by evaluating the post-dose tolerability of TSO in patients with Crohn's Disease via incidence of adverse events (i.e. # events) with a specific focus on reported gastrointestinal signs and symptoms
Time frame: 6 mo
Population: All patients who were randomized were treated according to the protocol and therefore were all included in the Safety Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Incidence of Adverse Events | 7 events |
| TSO 500 | Incidence of Adverse Events | 4 events |
| TSO 2500 | Incidence of Adverse Events | 1 events |
| TSO 7500 | Incidence of Adverse Events | 7 events |