a randomized, double-blind, placebo-controlled dose-escalation study to determine the safety and efficacy of intravenous infusion of human placenta-derived cells (pda001) for the treatment of crohn's disease

Conditions: Crohns Disease

Summary: to assess the safety and efficacy of intravenous (iv) pda001 infused every two weeks for up to 5 total infusions in subjects with crohn's disease who are refractory to one or more standard crohn's disease therapies.

this is a randomized, double-blind, placebo-controlled, dose-escalation study to study 3 cohorts of subjects with crohn's disease including (but not limited to) those with colonic involvement. each cohort (n = 9) will include pda001 treated subjects (n = 6) as well as placebo (vehicle control) treated subjects (n = 3). cohorts will be enrolled sequentially, beginning with the lowest dose cohort (1/4 unit pda001) and progressing until the maximum tolerated dose of iv pda001 is determined.

Eligibility criteria:
inclusion criteria: * • males and females 18 - 75 years of age at the time of signing the informed consent document. * minimum weight of subject is 40 kg at screening. * subject must have inflammatory crohn's disease (cd) diagnosed at least 6 months but no greater than 15 years prior to treatment with investigational product (ip). * subject must have confirmation of ongoing cd by ileocolonoscopy at screening. * subject must have a crohn's disease activity index (cdai) score ≥ 220 and ≤ 450 as assessed between visit 1 and visit 2. exclusion criteria: * subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study including but not limited to * liver function tests aspartate aminotransferase (ast) or alanine aminotransferase (alt) \> 2.5 x the upper limit of normal at screening. * serum creatinine concentration \> 2.0 mg/dl at screening. alkaline phosphatase \> 2.5 x the upper limit of normal at screening. * bilirubin level \> 2 mg/dl (unless subject has known gilbert's disease). * pregnant or lactating females. * morbidly obese subjects body mass index (bmi) \> 35 at screening). * subject has untreated chronic infection including clostridium difficile toxin positive at screening or treatment of any infection with antibiotics within 4 weeks prior to dosing with ip (other than a treated urinary tract infection or drained perianal abscess). note: stable doses of antibiotics used to treat crohn's disease are allowed. * subject has organic heart disease (eg, congestive heart failure), clinically significant arrhythmia or clinically significant abnormal findings on electrocardiograms (ecg). * subject has a history of other malignancies within 5 years (except basal cell carcinoma of the skin that is surgically cured, remote history of cancer now considered cured or positive pap smear with subsequent negative follow up). * subject has had a stricture of the bowel requiring hospitalization within 182 days prior to treatment with ip. * subject has had bowel surgery other than perianal (for example, fistulotomy, seton placement, or abscess drainage) or previous abscess drainage within 182 days prior to treatment with ip. * subject has had any surgery within 28 days prior to treatment with ip. * subject has a colostomy, ileostomy or ileal pouch anal anastomosis. * subject has received an investigational agent -an agent or device not approved by fda for marketed use in any indication-within 90 days (or 5 half-lives, whichever is longer) prior to treatment with investigational product. * subject has received previous cell therapy. * subject is expecting to have elective surgery at any time between visit 1 (screening) and visit 7 (end of induction phase). * subject has concurrent diagnosis of ulcerative colitis. * subjects with protein c or s deficiency. * subjects with prior history of thrombophlebitis or other pathological arterial or venous thrombosis.

Keywords: crohn's disease fistula diarrhea colon stem cells