A Study to Evaluate the Safety of PRV-300 in Adult Subjects With Moderately to Severely Active Ulcerative Colitis (PULSE)

A Phase 1b Study to Evaluate the Safety of PRV-300 Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis

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.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Biological: Placebo; Biological: PRV-300

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• Georgia
  • Tbilisi, Georgia
    • Clinical Site
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
    • Clinical Site
• Ukraine
  • Kapitanivka, Ukraine
    • Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PRV-300; Subjects in this arm will receive the study drug, PRV-300, via IV infusion, followed by an 8-week follow-up period.	Biological: PRV-300; Treatment
PLACEBO_COMPARATOR: Placebo; Subjects in this arm will receive placebo via IV infusion, followed by an 8-week follow-up period.	Biological: Placebo; Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-emergent adverse events (TEAEs),	Assessment of safety and tolerability	12 weeks

Collaborators and Investigators

• Sponsor: Provention Bio, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 21, 2018
• Primary Completion (ACTUAL): March 1, 2019
• Study Completion (ACTUAL): March 1, 2019

Study Registration Dates

• First Submitted: February 17, 2019
• First Submitted That Met QC Criteria: February 19, 2019
• First Posted (ACTUAL): February 21, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 13, 2020
• Last Update Submitted That Met QC Criteria: February 12, 2020
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Ulcerative Colitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: PRV-300-UC1b

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No