Clinical trial NCT00739986: Semapimod for Treatment of Moderate to Severe Crohn's Disease 1 or 3 Days' Treatment Versus Placebo
Official title: A Randomized, Double-Blind, Placebo-controlled Study of CNI-1493 for Treatment of Moderate to Severe Crohn's Disease 1 or 3 Days' Treatment vs. Placebo
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Crohn's Disease
Keywords: Crohn's Disease
TNF-alpha
IL-6
MAP Kinase
CNI-1493
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-08-22
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Assessment of the number of days' treatment with semapimod necessary for efficacy, as measured by response rate to CNI-1493 as compared to placebo, in patients with moderate to severe Crohn's disease (CD).


Eligibility criteria: Inclusion Criteria:

1. Men and women at least 18 years of age.
2. Baseline Crohn's Disease Activity Index (CDAI) 250-400.
3. Crohn's disease of at least 3 months duration, with colitis, ileitis, or ileocolitis, confirmed by radiography and/or endoscopy.
4. Those of childbearing potential were to use a barrier method (diaphragm or condom) of contraception and continue doing so for at least 3 months after last study medication. It was recommended that two forms be used.
5. Patients receiving medications for CD were to be on each medication for at least 8 weeks prior to screening and on stable doses of each for at least 2 weeks prior to screening, with the following exceptions:

   * those on methotrexate had to be on a stable dose for at least 4 weeks and not be receiving more than 25 mg/wk
   * those on azathioprine or 6-mercaptopurine on a stable dose for at least 10 weeks
   * those on steroids had to have been on steroids for at least 2 weeks and on a stable dose for those 2 weeks. They were not to be receiving more than 20 mg/day prednisone or equivalent
   * those on mesalazine had to have been on for at least 6 weeks and on a stable dose for at least 2 weeks
   * those on antibiotics for CD had to have been on for at least 2 weeks and on a stable dose for those 2 weeks
6. Any CD medication which had been discontinued was to have been discontinued at least 4 weeks prior to screening, with the exception of infliximab, which was to have been discontinued at least 8 weeks prior to screening.
7. The screening laboratory tests were to meet the following criteria:

   Hgb \>= 8.5 g/dL (5.3 mmol/L) WBC 3.5-20 x 109/L Neutrophils \>= 1.5 x 109/L Platelets \>= 100 x 109/L ALT (SGPT) \<1.5 x the upper limit of normal range Alkaline phosphatase \<2.5 x the upper limit of normal range Bilirubin \<25 mmol/L (1.5 mg/dl) Creatinine \<110 mol/L (1.2 mg/dl)
8. Patients were to be able to adhere to the study visit schedule and/or protocol requirements.
9. Patients were to be able to give informed consent and the consent was to be obtained prior to any study specific screening procedures.

Exclusion Criteria:

1. Treatment with any other experimental therapeutics within the last 4 weeks before enrolment.
2. History of tuberculosis, either clinically or as evidenced by a positive chest x-ray (exclusion criterion #8) or PPD.
3. Patients who had received anti-TNF therapy, such as infliximab, within 8 weeks of screening for this study. Patients who had received anti-TNF therapy \>8 weeks prior to screening were eligible.
4. Patients with any ostomy, extensive bowel resection (e.g., more than 100cm of small bowel, proctocolectomy or colectomy with ileorectal anastomosis). Segmental colectomy was permitted.
5. Patients immediately in need of surgery for active gastrointestinal bleeding, peritonitis, intestinal obstruction, or intra-abdominal or pancreatic abscess requiring surgical drainage.
6. Patients with known severe fixed symptomatic stenosis of the small or large intestine.
7. Evidence at the time of enrolment of bowel obstruction or history within the preceding six months as confirmed by radiography, endoscopy, or surgery.
8. Patients with a clinically significant abnormality or granulomata or any other evidence of primary tuberculosis infection on chest X-ray
9. Patients with current signs or symptoms of clinically significant hematologic, endocrine, pulmonary, cardiac, neurologic or cerebral disease.
10. Patients with previous diagnosis of, or known, malignancies.
11. Patients with serious infections, such as hepatitis, HIV, pneumonia or pyelonephritis, within 3 months prior to screening.
12. History of opportunistic infections such as herpes zoster within 2 months prior to screening, evidence of active CMV, active Pneumocystis carinii, drug resistant atypical mycobacterium.
13. Patients with stool examination positive for enteric pathogens, pathogenic ova or parasites, or Clostridium difficile toxin.
14. Women who were pregnant or breast-feeding.
15. A psychiatric, addictive, or any disorder that compromises ability to give truly informed consent for participation in this study.
16. Patients who had received CNI-1493 in the past.
17. More than three doses of NSAIDs, including aspirin and COX-2 inhibitors, within the two weeks prior to start of study medication

Primary outcomes:
measure: Crohn's Disease Activity Index (CDAI) score
timeFrame: Day 29
Secondary outcomes:
measure: Inflammatory Bowel Disease Questionnaire (IBDQ)
timeFrame: Day 29
measure: Crohn's disease endoscopic index of severity (CDEIS)
timeFrame: Day 29
measure: Change in level of C-reactive protein (CRP)
timeFrame: Day 29
measure: Safety (Adverse events)
timeFrame: Days 29 and 57
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Institute of Healthcare Assessment
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates
state: Georgia
city: Suwanee
country: United States
facility: Advanced Gastroenterology Associates
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Great Neck
country: United States
facility: Long Island Clinical Research Associates
state: New York
city: New York
country: United States
facility: Asher Kornbluth, MD
state: New York
city: Rochester
country: United States
facility: Rochester General Hospital
state: New York
city: Bristol
country: United States
facility: Gastroenterology Associates
state: Tennessee
city: Kingsport
country: United States
facility: Gastroenterology Associates
state: Tennessee
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: Academic Hospital Gasthuisberg
city: Berlin
country: Germany
facility: Benjamin Franklin University
city: Hannover
country: Germany
facility: Medizinischen Hochschule-Hannover
city: Heidelberg
country: Germany
facility: Universitats Klinikum Heidelberg
city: Kiel
country: Germany
facility: University of Kiel
city: Minden
country: Germany
facility: Gastroenterologische Fachpraxis
city: Muenster
country: Germany
facility: University of Munster
city: Munchen
country: Germany
facility: Stadtisches Krankenhaus Munchen-Bogenhausen
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Hospital
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Tel Hashomer
country: Israel
facility: Chaim Sheba Medical Center
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Amsterdam
country: Netherlands
facility: Free University (Vrije Universiteit)
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
Study officials:
affiliation: Academic Medical Center, Netherlands
name: Daan Hommes, MD
role: PRINCIPAL_INVESTIGATOR
References: