A First Time in Human Study in Healthy Volunteers and Patients

A Four Part, Phase 1, First Time in Human, Single Centre Study in Healthy Male Subjects, Patient Volunteers With Crohn's Disease and in Healthy Patient Volunteers With a Terminal Ileostomy

A multi-part study to investigate the safety, tolerability and local and systemic pharmacokinetics of V565

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: V565; Drug: V565; Drug: V565; Drug: V565; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 1YR
    • Quintiles Drug Research Unit at Guy's Hospital, Quintiles Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Parts 1 and 2

  1. Adult male subjects aged 18 to 45 years inclusive.
  2. Body mass index (BMI) between 18.0 and 32.0 kg/m2 inclusive.
  3. Body weight between 50.0 and 100.0 kg inclusive.
  4. Subjects who are healthy as determined by pre study medical history, physical examination and 12-lead ECG, and clinical laboratory tests

• Part 3

  1. Adult male or female subjects aged 18 to 65 years.
  2. Ileostomy for a minimum of 18 months for a non malignant disease indication.
  3. A BMI between 18.0 and 32.0 kg/m2 inclusive.
  4. Body weight between 50.0 and 100.0 kg inclusive.
  5. Subjects who are healthy as determined by pre study medical history, physical examination and 12-lead ECG, and clinical laboratory tests

• Part 4

  1. Adult male or female subjects aged 18 to 65 years.
  2. A confirmed diagnosis of Crohn's disease for a minimum of 6 months.
  3. A BMI between 15.0 and 32.0 kg/m2 inclusive.
  4. Subjects who have no other significant co-morbidity (other than those associated with Crohn's disease).
  5. Subjects whose medical history, physical examination, clinical laboratory test results and 12-lead ECG have no clinically relevant abnormalities (other than those associated with Crohn's disease).

Exclusion Criteria:

• Parts 1 and 2

  1. A clinically significant abnormal medical history or clinically significant abnormal physical examination, including history of febrile illness within 1 week prior to the first dose.
  2. A history of severe allergies, non-allergic drug reactions, or multiple drug allergies.
  3. A known hypersensitivity to TNF inhibitors or any of the inactive ingredients of the study treatment.
  4. A history of significant gastrointestinal (GI) disease, including GI motility disorders, GI malignancy or of polyposis coli.
  5. Previous surgery to the GI tract with the exception of appendectomy.
  6. A history of malignancy.
  7. Any other condition which in the investigator's opinion will interfere with the trial or interpretation of the results.

• Part 3

  1. A history of Crohn's disease.
  2. A clinically significant abnormal medical history (other than the condition leading to ileostomy) or clinically significant abnormal physical examination, including history of febrile illness within 1 week prior to the first dose.
  3. A history of severe allergies, non-allergic drug reactions, or multiple drug allergies.
  4. A known hypersensitivity or contraindication to TNF inhibitors or any of the inactive ingredients of the study treatment.
  5. A known history of heart disease.
  6. Any clinical evidence of active inflammatory bowel disease.
  7. Any other condition which in the investigator's opinion will interfere with the trial or interpretation of the results.

• Part 4

  1. Subjects with severe Crohn's disease such as: those requiring surgery; those with a current abscess; those with a non inflammatory stricture; those with a history of obstruction.
  2. Having ever received anti-TNF-α therapy or other biologics.
  3. Required an increase in dose of either steroids or immunosuppressant therapy within the past 6 weeks.

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part 1; Single ascending dose of oral V565	Drug: V565; single ascending dose of V565; Drug: V565; Multiple dose; Drug: V565; Open-label single dose; Drug: V565; Open-label single ascending dose
EXPERIMENTAL: Part 2 - V565; Single dose level of oral V565 TID for 14 days	Drug: V565; single ascending dose of V565; Drug: V565; Multiple dose; Drug: V565; Open-label single dose; Drug: V565; Open-label single ascending dose
PLACEBO_COMPARATOR: Part 1 and 2 - placebo; Oral placebo single dose (Part 1) or TID for 14 days (Part 2)	Drug: Placebo; Single and multiple dose
EXPERIMENTAL: Part 3; Single dose of V565 in patient volunteers	Drug: V565; single ascending dose of V565; Drug: V565; Multiple dose; Drug: V565; Open-label single dose; Drug: V565; Open-label single ascending dose
EXPERIMENTAL: Part 4; Single ascending dose of V565 in patients with Crohn's Disease	Drug: V565; single ascending dose of V565; Drug: V565; Multiple dose; Drug: V565; Open-label single dose; Drug: V565; Open-label single ascending dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety & tolerability: treatment-emergent AEs including clinically significant changes in physical examinations, safety lab tests, ECGs or vital signs	Up to 14 days
Measurement of the concentrations of V565 in ileal fluid following a single dose	24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Evaluation of pharmacokinetic parameter of V565: Cmax	72 hours
Evaluation of pharmacokinetic parameter of V565: AUC	72 hours
Evaluation of pharmacokinetic parameter of V565: tmax	72 hours

Collaborators and Investigators

• Sponsor: VHsquared Ltd.

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (ACTUAL): March 1, 2016
• Study Completion (ACTUAL): March 1, 2016

Study Registration Dates

• First Submitted: December 12, 2016
• First Submitted That Met QC Criteria: January 4, 2017
• First Posted (ESTIMATE): January 5, 2017

Study Record Updates

• Last Update Posted (ESTIMATE): January 5, 2017
• Last Update Submitted That Met QC Criteria: January 4, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: V56501

Plan for Individual participant data (IPD)

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