a study to evaluate the safety of prv-300 in adult subjects with moderately to severely active ulcerative colitis

Conditions: Ulcerative Colitis

Summary: the purpose of this study is to evaluate the safety and tolerability of prv-300 for 12 weeks in subjects with active ulcerative colitis. subjects will receive either prv-300 or placebo treatment. each group will receive study drug over a total of 12 weeks, followed by an 8-week safety follow-up period.

this is a phase 1b, randomized, double-blind, placebo-controlled, parallel-group, multicenter study in adult subjects with moderately to severely active uc. randomization will be stratified by mayo score. subjects will receive either prv-300 or placebo treatment. each group will receive study drug over a total of 12 weeks, followed by an 8-week safety follow-up period. the total duration of the study will be 20 weeks, excluding the screening period. the primary objective is to evaluate the safety and tolerability of prv-300 for 12 weeks in subjects with active uc. the secondary objectives are to evaluate the effect of prv-300 for 12 weeks in subjects with active uc on: * pharmacodynamics: changes in gene scores in colonic biopsies over the course of treatment. * pharmacokinetics: peak (cmax) and trough (cmin) serum concentrations of prv-300 in subjects with active uc. * immunogenicity: immunogenicity of prv-300 in subjects with active uc * endoscopic: trends in endoscopic disease activity in subjects with active uc.

Eligibility criteria:
inclusion criteria: 1. subject must be a man or woman aged 18-75 years, inclusive. 2. subject has a clinical diagnosis of uc at least 3 months before screening. 3. subject has moderately to severely active uc, defined as a mayo score of 6 to 12, inclusive, at screening. 4. subject has a mayo endoscopic subscore of ≥2 based on central read of the video sigmoidoscopy at screening. 5. subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol. exclusion criteria: 1. subject has severe extensive colitis as evidenced by any of the following: 1. current hospitalization for the treatment of uc. 2. investigator judgment that the subject is likely to require a colectomy within 12 weeks of baseline. 3. temperature ≥37.8 ºc (oral or tympanic) and a heart rate \>90 bpm. 2. subject has uc limited to \<15 cm of the colon. 3. subject has a diagnosis of cd or the presence or history of fistula or indeterminate colitis. 4. presence of a gastrostomy, jejunostomy, ileostomy or colostomy. 5. subject has had or is expected to have surgery for active gastrointestinal bleeding, peritonitis, intestinal obstruction, or intra-abdominal or pancreatic abscess requiring surgical drainage, or other conditions that may confound study evaluations from 2 months before screening through the end of this study. 6. presence of symptomatic colonic or small bowel obstruction 7. history of colonic resection 8. history of colonic mucosal high-grade dysplasia 9. subject has chronic or recurrent infectious disease 10. subject has positive serology to human immunodeficiency virus (hiv) 1 or 2, hepatitis b virus (hbv) or hepatitis c virus (hcv) at screening. 11. subject has any known malignancy or has a history of malignancy (with the exception of basal cell carcinoma; squamous cell carcinoma in situ of the skin; or cervical carcinoma in situ that has been treated with no evidence of recurrence; or squamous cell carcinoma of the skin that has been treated with no evidence of recurrence within 5 years before screening). 12. subject has ever received prv-300 (or cnto 3157) or has known allergies, hypersensitivity, or intolerance to prv-300 or its excipients; or known or suspected intolerance or hypersensitivity to any biologic medication or known allergies or clinically significant reactions to murine, chimeric, or human proteins, to monoclonal antibodies or antibody fragments; or a history of severe allergic reactions, angioedema, or anaphylaxis that might suggest risk for a reaction to a biologic agent. 13. subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.

Keywords: ulcerative colitis