Semapimod for Treatment of Moderate to Severe Crohn's Disease 1 or 3 Days' Treatment Versus Placebo

Inclusion criteria

• Men and women at least 18 years of age.
• Baseline Crohn's Disease Activity Index (CDAI) 250-400.
• Crohn's disease of at least 3 months duration, with colitis, ileitis, or ileocolitis, confirmed by radiography and/or endoscopy.
• 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.
• 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
• 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.
• 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)

• Patients were to be able to adhere to the study visit schedule and/or protocol requirements.
• 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

• Treatment with any other experimental therapeutics within the last 4 weeks before enrolment.
• History of tuberculosis, either clinically or as evidenced by a positive chest x-ray (exclusion criterion #8) or PPD.
• 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.
• 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.
• Patients immediately in need of surgery for active gastrointestinal bleeding, peritonitis, intestinal obstruction, or intra-abdominal or pancreatic abscess requiring surgical drainage.
• Patients with known severe fixed symptomatic stenosis of the small or large intestine.
• Evidence at the time of enrolment of bowel obstruction or history within the preceding six months as confirmed by radiography, endoscopy, or surgery.
• Patients with a clinically significant abnormality or granulomata or any other evidence of primary tuberculosis infection on chest X-ray
• Patients with current signs or symptoms of clinically significant hematologic, endocrine, pulmonary, cardiac, neurologic or cerebral disease.
• Patients with previous diagnosis of, or known, malignancies.
• Patients with serious infections, such as hepatitis, HIV, pneumonia or pyelonephritis, within 3 months prior to screening.
• 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.
• Patients with stool examination positive for enteric pathogens, pathogenic ova or parasites, or Clostridium difficile toxin.
• Women who were pregnant or breast-feeding.
• A psychiatric, addictive, or any disorder that compromises ability to give truly informed consent for participation in this study.
• Patients who had received CNI-1493 in the past.
• More than three doses of NSAIDs, including aspirin and COX-2 inhibitors, within the two weeks prior to start of study medication