Clinical trial NCT03849599: A Study to Evaluate the Safety of PRV-300 in Adult Subjects With Moderately to Severely Active Ulcerative Colitis
Official title: A Phase 1b Study to Evaluate the Safety of PRV-300 Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ulcerative Colitis
Keywords: Ulcerative Colitis
Lead sponsor: Provention Bio, Inc.
Sponsor class: INDUSTRY
First posted: 2019-02-21
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

Primary outcomes:
measure: Incidence of Treatment-emergent adverse events (TEAEs),
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Tbilisi
country: Georgia
facility: Clinical Site
city: Chisinau
country: Moldova, Republic of
facility: Clinical Site
city: Kapitanivka
country: Ukraine
facility: Clinical Site
Study officials:
affiliation: Provention Bio
name: Provention Bio, MD
role: STUDY_DIRECTOR
References: