Crohn's Disease
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of V565 in participants with active Crohn's Disease (CD).
Detailed description
This study will be a multiple-site, double-blind, placebo-controlled, parallel-group study in approximately 126 subjects with a confirmed diagnosis of CD for at least three months and have CD involving the ileum and/or colon. Following a screening period of up to 28 days, subjects will be randomly allocated into one of two treatment arms: either V565 or placebo using a 2:1 active:placebo ratio for a treatment period of 6 weeks. Subjects will be treated with study drug as an add-on to any permitted stable medications already being taken for CD.
Interventions
DRUGV565
Daily dosing of V565 three times a day orally for 6 weeks
DRUGPlacebo
Daily dosing of placebo three times a day orally for 6 weeks
Sponsors
VHsquared Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* History of Crohn's Disease of at least 3 months duration prior to screening * Crohn's Disease Activity Index (CDAI) score of ≥220 to ≤450 during screening * C-reactive protein (CRP) ≥5 mg/L (or, if CRP is normal, faecal calprotectin (FCP) ≥250 µg/g) at screening * Permitted CD medication regimen expected to remain stable during the period of the study
Exclusion criteria
* Previous lack of response or current contra-indication to an anti-tumour necrosis factor α (anti-TNFα) agent * Certain complications of Crohn's Disease that would make it hard to assess response to study drug * Known history or suspicion of inflammatory bowel disease other than Crohn's disease * History of tuberculosis (TB) or latent TB infection that has not been treated * Any significant illness or condition which would preclude effective participation in the study * GI infection as demonstrated by presence of enteric pathogens * Pregnant or lactating women * Abdominal surgery in the previous 6 months * Unsuitable for inclusion in the study in the opinion of the investigator or sponsor for any reason that may compromise the subject's safety or confound data interpretation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Achieving Response to Therapy, Defined as Reduction in the CDAI Score and in Inflammatory Markers CRP or FCP at Day 42. | Day 42 | Number of responders at Day 42, defined as subjects achieving both CDAI ≥ 70-point reduction from baseline or CDAI score \< 150, and a reduction of ≥ 40% from the baseline value of CRP or FCP. Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI \< 150, and very severe disease is defined as CDAI \> 450. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Achieving Response to Therapy, Defined as Reduction in the CDAI Score and in Inflammatory Markers CRP or FCP at Day 42. | Day 42 | Number of subjects achieving a ≥ 100-point reduction in CDAI score and a concomitant reduction of at least 50% in CRP or FCP at Day 42 Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI \< 150, and very severe disease is defined as CDAI \> 450. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Improvement in Endoscopic Mucosal Appearance | Day 42 | Subjects with a pre-treatment endoscopy Simple Endoscopic Score for Crohn's Disease (SES-CD) of at least 7 (4 if disease was confined to ileum) had a post-treatment endoscopy to evaluate changes in mucosal appearance. The central reader of the endoscopies, blinded to treatment and sequence, was asked to grade if video A was better or worse than video B. Pre- and post-treatment videos were randomly assigned to A and B. The endpoint is the number of subjects whose post-treatment endoscopy was better than their pre-treatment endoscopy. |
| Number of Subjects Achieving CRP Levels Within Normal Limits at Days 14 and 42 | Days 14 and 42 | The number of subjects who entered the study with an elevated CRP who had a CRP level within normal limits at Days 14 and 42. Normal levels defined as CRP less than or equal to 5mg/L |
| Number of Subjects Achieving FCP Levels Within Normal Limits at Day 14 and 42 | Days 14 and 42 | The number of subjects who entered the study with an elevated FCP who had an FCP level within normal limits at Days 14 and 42. Normal limits of FCP defined as less than or equal to 250µg/g |
Countries
Austria, Canada, Czechia, Germany, Hungary, Netherlands, Norway, Poland, Serbia, Slovakia, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| V565 V565 TID PO for 6 weeks
V565: Daily dosing of V565 three times a day orally for 6 weeks | 82 |
| Placebo Placebo TID PO for 6 weeks
Placebo: Daily dosing of placebo three times a day orally for 6 weeks | 43 |
| Total | 125 |
Baseline characteristics
| Characteristic | Total | V565 | Placebo |
|---|---|---|---|
| Age, Continuous | 37.5 years STANDARD_DEVIATION 13.36 | 37.7 years STANDARD_DEVIATION 14.05 | 37.2 years STANDARD_DEVIATION 12.08 |
| Baseline C-Reactive Protein (CRP) | 20.8 mg/L STANDARD_DEVIATION 17.13 | 59 mg/L STANDARD_DEVIATION 21.9 | 18.7 mg/L STANDARD_DEVIATION 14.56 |
| Baseline Crohn's Disease Activity Index | 309.69 units on a scale STANDARD_DEVIATION 69.379 | 316.34 units on a scale STANDARD_DEVIATION 71.283 | 296.69 units on a scale STANDARD_DEVIATION 64.334 |
| Baseline Faecal Calprotectin (FCP) | 1085.224 µg/g STANDARD_DEVIATION 843.5207 | 1082.619 µg/g STANDARD_DEVIATION 804.2154 | 1091.217 µg/g STANDARD_DEVIATION 974.0855 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 121 Participants | 82 Participants | 39 Participants |
| Region of Enrollment Austria | 3 participants | 3 participants | 0 participants |
| Region of Enrollment Canada | 2 participants | 1 participants | 1 participants |
| Region of Enrollment Czechia | 29 participants | 18 participants | 11 participants |
| Region of Enrollment Germany | 6 participants | 4 participants | 2 participants |
| Region of Enrollment Hungary | 5 participants | 4 participants | 1 participants |
| Region of Enrollment Netherlands | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Norway | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Poland | 14 participants | 9 participants | 5 participants |
| Region of Enrollment Serbia | 6 participants | 5 participants | 1 participants |
| Region of Enrollment Slovakia | 8 participants | 6 participants | 2 participants |
| Region of Enrollment Ukraine | 34 participants | 22 participants | 12 participants |
| Region of Enrollment United Kingdom | 9 participants | 4 participants | 5 participants |
| Region of Enrollment United States | 7 participants | 4 participants | 3 participants |
| Sex: Female, Male Female | 51 Participants | 32 Participants | 19 Participants |
| Sex: Female, Male Male | 74 Participants | 50 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 82 | 0 / 43 |
| other Total, other adverse events | 30 / 82 | 16 / 43 |
| serious Total, serious adverse events | 3 / 82 | 2 / 43 |
Outcome results
Primary
Number of Subjects Achieving Response to Therapy, Defined as Reduction in the CDAI Score and in Inflammatory Markers CRP or FCP at Day 42.
Number of responders at Day 42, defined as subjects achieving both CDAI ≥ 70-point reduction from baseline or CDAI score \< 150, and a reduction of ≥ 40% from the baseline value of CRP or FCP. Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI \< 150, and very severe disease is defined as CDAI \> 450.
Time frame: Day 42
Population: Intent-to-treat population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| V565 | Number of Subjects Achieving Response to Therapy, Defined as Reduction in the CDAI Score and in Inflammatory Markers CRP or FCP at Day 42. | 29 Participants |
| Placebo | Number of Subjects Achieving Response to Therapy, Defined as Reduction in the CDAI Score and in Inflammatory Markers CRP or FCP at Day 42. | 16 Participants |
Secondary
Number of Subjects Achieving Response to Therapy, Defined as Reduction in the CDAI Score and in Inflammatory Markers CRP or FCP at Day 42.
Number of subjects achieving a ≥ 100-point reduction in CDAI score and a concomitant reduction of at least 50% in CRP or FCP at Day 42 Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI \< 150, and very severe disease is defined as CDAI \> 450.
Time frame: Day 42
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| V565 | Number of Subjects Achieving Response to Therapy, Defined as Reduction in the CDAI Score and in Inflammatory Markers CRP or FCP at Day 42. | 20 Participants |
| Placebo | Number of Subjects Achieving Response to Therapy, Defined as Reduction in the CDAI Score and in Inflammatory Markers CRP or FCP at Day 42. | 9 Participants |
Other Pre-specified
Number of Subjects Achieving CRP Levels Within Normal Limits at Days 14 and 42
The number of subjects who entered the study with an elevated CRP who had a CRP level within normal limits at Days 14 and 42. Normal levels defined as CRP less than or equal to 5mg/L
Time frame: Days 14 and 42
Population: Patients were enrolled into the study based on either a baseline CRP measurement or a baseline FCP measurement. Only the subjects who entered the study based on their CRP measurement are included here.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| V565 | Number of Subjects Achieving CRP Levels Within Normal Limits at Days 14 and 42 | 11 Participants |
| Placebo | Number of Subjects Achieving CRP Levels Within Normal Limits at Days 14 and 42 | 4 Participants |
Other Pre-specified
Number of Subjects Achieving FCP Levels Within Normal Limits at Day 14 and 42
The number of subjects who entered the study with an elevated FCP who had an FCP level within normal limits at Days 14 and 42. Normal limits of FCP defined as less than or equal to 250µg/g
Time frame: Days 14 and 42
Population: Patients were enrolled into the study based on either a baseline CRP measurement or a baseline FCP measurement. Only the subjects who entered the study based on their FCP measurement are included here.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| V565 | Number of Subjects Achieving FCP Levels Within Normal Limits at Day 14 and 42 | 7 Participants |
| Placebo | Number of Subjects Achieving FCP Levels Within Normal Limits at Day 14 and 42 | 3 Participants |
Other Pre-specified
Number of Subjects With Improvement in Endoscopic Mucosal Appearance
Subjects with a pre-treatment endoscopy Simple Endoscopic Score for Crohn's Disease (SES-CD) of at least 7 (4 if disease was confined to ileum) had a post-treatment endoscopy to evaluate changes in mucosal appearance. The central reader of the endoscopies, blinded to treatment and sequence, was asked to grade if video A was better or worse than video B. Pre- and post-treatment videos were randomly assigned to A and B. The endpoint is the number of subjects whose post-treatment endoscopy was better than their pre-treatment endoscopy.
Time frame: Day 42
Population: Only those subjects who had a second endoscopy are included in this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| V565 | Number of Subjects With Improvement in Endoscopic Mucosal Appearance | 18 Participants |
| Placebo | Number of Subjects With Improvement in Endoscopic Mucosal Appearance | 3 Participants |