Colitis, Ulcerative
Conditions
Keywords
S1P; sphingosine 1 phosphate receptor;, Ventyx; Oppilan;, moderate or severe ulcerative colitis
Brief summary
This is a study to understand if taking VTX002 daily as a tablet orally is safe and effective in participants diagnosed with moderate to severe ulcerative colitis (UC). Approximately 189 participants will take VTX002 Dose A, VTX002 Dose B, or matching placebo, once daily. The study consists of a 28-day Screening Period (to see if a participant qualifies for the study), a 13-week double-blind period (a participant receives either active Dose A, Dose B or Placebo), a Long-Term Extension (LTE) Treatment Period of up to 39 weeks, an Open-Label Extension (OLE) Treatment Period of up to 143 weeks, and a 2-week Follow-Up Period. The maximal duration of treatment including the Induction Period, LTE and OLE will be 36 months.
Detailed description
This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of VTX002 in subjects with moderately to severely active UC following daily oral administration of VTX002 as a tablet. Approximately 189 eligible subjects will be randomized in a 1:1:1 ratio to receive VTX002 Dose A, VTX002 Dose B, or matching placebo, once daily (approximately 63 subjects per treatment group). The study consists of a 28-day Screening Period, a 13-week double-blind Induction Treatment Period (including 7 days of titration followed by 12 weeks of treatment at the assigned dose), a Long-Term Extension (LTE) Treatment Period of up to 39 weeks, an Open-Label Extension (OLE) Treatment Period of up to 143 weeks, and a 2-week Follow-Up Period. The maximal duration of treatment including the Induction Period, LTE and OLE will be 36 months. Objectives Primary Objective • Assess the efficacy of VTX002 when administered for 13 weeks on clinical remission Secondary Objectives * Assess the efficacy of VTX002 when administered for 13 weeks on endoscopic changes, symptomatic response and remission, histology, and mucosal healing * Assess the safety and tolerability of VTX002 * Assess the pharmacokinetics (PK) of VTX002 Long-Term and Open-Label Extension Objectives * Assess the efficacy of VTX002 through the LTE and OLE Treatment Periods on endoscopic changes, symptomatic response and remission, histology, and mucosal healing * Assess the safety of VTX002 through the LTE and OLE Treatment Periods
Interventions
DRUGVTX002
Dose A tablet administered orally once daily
DRUGPlacebo
Placebo Tablet for VTX002 administered orally once daily
Sponsors
Oppilan Pharma Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The study will employ a double-blind design. Subjects, Investigators, study center staff, persons performing the assessments, central endoscopy readers and the Sponsor are to remain blinded to the identity of the Induction Period treatment from the time of randomization until the interim database lock for the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with UC ≥ 3 months prior to Screening. * Active UC confirmed by endoscopy
Exclusion criteria
* Severe extensive colitis * Diagnosis of Crohn's disease (CD) or indeterminate colitis or the presence or history of a fistula consistent with CD * Diagnosis of microscopic colitis, ischemic colitis, or infectious colitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Remission at 13 Weeks | Day 1 of Induction treatment period to Week 13 | The percentage of participants with clinical remission at Week 13. Clinical remission was based on the modified Mayo score (MMS), which is a composite score of participant-reported symptoms and endoscopies which were assessed by a central reader. Clinical remission was defined as stool frequency (SF) subscore = 0 or 1, rectal bleeding (RB) subscore = 0, and endoscopic subscore (ES) ≤ 1 (excluding friability). Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Endoscopic Improvement at Week 13 | Day 1 of Induction Treatment Period to Week 13 | The percentage of participants with endoscopic improvement at Week 13. Endoscopic improvement was assessed from endoscopies assessed by a central reader. Endoscopic improvement was defined as ES ≤ 1 (excluding friability). The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease). |
| Symptomatic Remission at Week 13 | Day 1 of Induction Treatment Period to Week 13 | The percentage of participants with symptomatic remission at Week 13. Symptomatic remission was measured using participant-reported symptoms and was defined as SF subscore = 0 or 1 and RB subscore = 0. The SF subscore ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB subscore ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). Higher scores indicate more severe disease. |
| Histologic Remission at Week 13 | Day 1 of Induction Treatment Period to Week 13 | The percentage of participants with histologic remission at Week 13. Histologic remission was assessed using the Geboes Index score and defined for this outcome measure as a Geboes score \< 2.0. The Geboes score grading system is a validated score for evaluating histologic disease activity in ulcerative colitis and is graded on a scale of 0 to 5. A higher Geboes score indicates more severe disease. |
| Endoscopic Improvement-Histologic Remission at Week 13 | Day 1 of Induction Treatment Period to Week 13 | The percentage of participants with endoscopic improvement-histologic remission at Week 13. This outcome measure was assessed by endoscopic histologic scores and defined as ES ≤ 1 (excluding friability) and a Geboes Index score \< 2.0. The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease). The Geboes score grading system is a validated score for evaluating histologic disease activity in ulcerative colitis and is graded on a scale of 0 to 5. A higher Geboes score indicates more severe disease. |
| PK of VTX002 | Weeks 1, 4, 8, and 13 of the Induction Treatment Period | Plasma concentrations of VTX002 in samples obtained predose at Weeks 1, 4, 8, and 13 in the Induction Treatment Period |
Countries
Bulgaria, Czechia, France, Georgia, Germany, Hungary, India, Italy, Lithuania, Poland, Serbia, Slovakia, South Korea, United States
Contacts
STUDY_DIRECTORSnehal Naik, PhD
Ventyx Biosciences, Inc
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VTX002 60 mg Once Daily VTX002 60 mg tablet administered orally once daily | 70 |
| VTX002 30 mg Once Daily VTX002 30 mg tablet administered orally once daily | 73 |
| Placebo Once Daily Placebo tablet administered orally once daily | 70 |
| Total | 213 |
Baseline characteristics
| Characteristic | VTX002 60 mg Once Daily | VTX002 30 mg Once Daily | Placebo Once Daily | Total |
|---|---|---|---|---|
| Age, Continuous | 39.4 years STANDARD_DEVIATION 13.81 | 42.3 years STANDARD_DEVIATION 15.01 | 40.1 years STANDARD_DEVIATION 13.78 | 40.6 years STANDARD_DEVIATION 14.21 |
| Age, Customized 18 to 44 | 49 Participants | 41 Participants | 46 Participants | 136 Participants |
| Age, Customized 45 to 65 | 18 Participants | 27 Participants | 21 Participants | 66 Participants |
| Age, Customized >65 | 3 Participants | 5 Participants | 3 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 7 Participants | 3 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 67 Participants | 66 Participants | 66 Participants | 199 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 4 Participants | 7 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 60 Participants | 67 Participants | 63 Participants | 190 Participants |
| Sex: Female, Male Female | 39 Participants | 26 Participants | 32 Participants | 97 Participants |
| Sex: Female, Male Male | 31 Participants | 47 Participants | 38 Participants | 116 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 70 | 0 / 73 | 0 / 70 | 0 / 33 | 0 / 37 | 0 / 25 | 0 / 190 |
| other Total, other adverse events | 10 / 70 | 10 / 73 | 9 / 70 | 3 / 33 | 8 / 37 | 1 / 25 | 79 / 190 |
| serious Total, serious adverse events | 3 / 70 | 2 / 73 | 0 / 70 | 0 / 33 | 2 / 37 | 2 / 25 | 8 / 190 |
Outcome results
Primary
Clinical Remission at 13 Weeks
The percentage of participants with clinical remission at Week 13. Clinical remission was based on the modified Mayo score (MMS), which is a composite score of participant-reported symptoms and endoscopies which were assessed by a central reader. Clinical remission was defined as stool frequency (SF) subscore = 0 or 1, rectal bleeding (RB) subscore = 0, and endoscopic subscore (ES) ≤ 1 (excluding friability). Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease.
Time frame: Day 1 of Induction treatment period to Week 13
Population: Full Analysis Set - Baseline Modified Mayo Score 5-9
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VTX002 60 mg Once Daily | Clinical Remission at 13 Weeks | 19 Participants |
| VTX002 30 mg Once Daily | Clinical Remission at 13 Weeks | 17 Participants |
| Placebo Once Daily | Clinical Remission at 13 Weeks | 8 Participants |
Comparison: At 13 weeksp-value: 0.018495% CI: [2.58, 29.05]Cochran-Mantel-Haenszel
Comparison: At 13 weeksp-value: 0.04195% CI: [-0.03, 25.58]Cochran-Mantel-Haenszel
Secondary
Endoscopic Improvement at Week 13
The percentage of participants with endoscopic improvement at Week 13. Endoscopic improvement was assessed from endoscopies assessed by a central reader. Endoscopic improvement was defined as ES ≤ 1 (excluding friability). The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease).
Time frame: Day 1 of Induction Treatment Period to Week 13
Population: Full Analysis Set - Baseline MMS 5 to 9
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VTX002 60 mg Once Daily | Endoscopic Improvement at Week 13 | 25 Participants |
| VTX002 30 mg Once Daily | Endoscopic Improvement at Week 13 | 23 Participants |
| Placebo Once Daily | Endoscopic Improvement at Week 13 | 11 Participants |
Comparison: At 13 weeksp-value: 0.00795% CI: [5.73, 34.42]Cochran-Mantel-Haenszel
Comparison: At Week 13p-value: 0.016295% CI: [2.75, 30.67]Cochran-Mantel-Haenszel
Secondary
Endoscopic Improvement-Histologic Remission at Week 13
The percentage of participants with endoscopic improvement-histologic remission at Week 13. This outcome measure was assessed by endoscopic histologic scores and defined as ES ≤ 1 (excluding friability) and a Geboes Index score \< 2.0. The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease). The Geboes score grading system is a validated score for evaluating histologic disease activity in ulcerative colitis and is graded on a scale of 0 to 5. A higher Geboes score indicates more severe disease.
Time frame: Day 1 of Induction Treatment Period to Week 13
Population: Full Analysis Set - Baseline MMS 5 to 9
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VTX002 60 mg Once Daily | Endoscopic Improvement-Histologic Remission at Week 13 | 7 Participants |
| VTX002 30 mg Once Daily | Endoscopic Improvement-Histologic Remission at Week 13 | 14 Participants |
| Placebo Once Daily | Endoscopic Improvement-Histologic Remission at Week 13 | 0 Participants |
Comparison: At Week 13p-value: 0.0072Cochran-Mantel-Haenszel
Comparison: At Week 13p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Histologic Remission at Week 13
The percentage of participants with histologic remission at Week 13. Histologic remission was assessed using the Geboes Index score and defined for this outcome measure as a Geboes score \< 2.0. The Geboes score grading system is a validated score for evaluating histologic disease activity in ulcerative colitis and is graded on a scale of 0 to 5. A higher Geboes score indicates more severe disease.
Time frame: Day 1 of Induction Treatment Period to Week 13
Population: Full analysis set - Baseline MMS 5 to 9
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VTX002 60 mg Once Daily | Histologic Remission at Week 13 | 13 Participants |
| VTX002 30 mg Once Daily | Histologic Remission at Week 13 | 20 Participants |
| Placebo Once Daily | Histologic Remission at Week 13 | 5 Participants |
p-value: 0.049995% CI: [-0.99, 23.38]Cochran-Mantel-Haenszel
Comparison: At Week 13p-value: 0.001195% CI: [7.94, 33.53]Cochran-Mantel-Haenszel
Secondary
PK of VTX002
Plasma concentrations of VTX002 in samples obtained predose at Weeks 1, 4, 8, and 13 in the Induction Treatment Period
Time frame: Weeks 1, 4, 8, and 13 of the Induction Treatment Period
Population: The Pharmacokinetics Set consisted of all participants who received VTX002 and had at least 1 measured concentration at a scheduled PK timepoint after start of dosing for VTX002.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VTX002 60 mg Once Daily | PK of VTX002 | Week 1 | 640.8 ng/mL | Standard Deviation 378.77 |
| VTX002 60 mg Once Daily | PK of VTX002 | Week 4 | 911.5 ng/mL | Standard Deviation 777.4 |
| VTX002 60 mg Once Daily | PK of VTX002 | Week 8 | 935.1 ng/mL | Standard Deviation 718.16 |
| VTX002 60 mg Once Daily | PK of VTX002 | Week 13 | 1050 ng/mL | Standard Deviation 930.15 |
| VTX002 30 mg Once Daily | PK of VTX002 | Week 13 | 444.2 ng/mL | Standard Deviation 341.13 |
| VTX002 30 mg Once Daily | PK of VTX002 | Week 1 | 363.2 ng/mL | Standard Deviation 237.79 |
| VTX002 30 mg Once Daily | PK of VTX002 | Week 8 | 393.2 ng/mL | Standard Deviation 251.98 |
| VTX002 30 mg Once Daily | PK of VTX002 | Week 4 | 374.7 ng/mL | Standard Deviation 242.93 |
Secondary
Symptomatic Remission at Week 13
The percentage of participants with symptomatic remission at Week 13. Symptomatic remission was measured using participant-reported symptoms and was defined as SF subscore = 0 or 1 and RB subscore = 0. The SF subscore ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB subscore ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). Higher scores indicate more severe disease.
Time frame: Day 1 of Induction Treatment Period to Week 13
Population: Full analysis set - Baseline MMS 5 to 9
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VTX002 60 mg Once Daily | Symptomatic Remission at Week 13 | 29 Participants |
| VTX002 30 mg Once Daily | Symptomatic Remission at Week 13 | 29 Participants |
| Placebo Once Daily | Symptomatic Remission at Week 13 | 18 Participants |
p-value: 0.044895% CI: [0.65, 31.37]Cochran-Mantel-Haenszel
Comparison: At Week 13p-value: 0.041795% CI: [0.23, 30.58]Cochran-Mantel-Haenszel