| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderately to Severely Active Ulcerative Colitis |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10045365 |
| E.1.2 | Term | Ulcerative colitis |
| E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| Assess the efficacy of VTX002 when administered for 13 weeks on clinical remission. |
|
| E.2.2 | Secondary objectives of the trial |
• 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 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Men or women, 18 to 80 years of age, inclusive, at the time of consent.
2. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed Consent Form.
3. Diagnosed with UC ≥ 3 months prior to Screening. The diagnosis of UC must be confirmed by endoscopic and histologic evidence. The endoscopy and histology report should be present in the source documents; however, if not available, the Screening endoscopy and histology may serve as such.
4. Active UC confirmed by endoscopy with ≥ 10 cm rectal involvement. Participants with proctitis only at baseline who meet the other eligibility criteria for inclusion, including the endoscopic and rectal bleeding criteria for moderate to severe disease, will be capped at 10% of the total participants enrolled.
5. Moderately to severely active UC, defined as an MMS of 5 to 9, including an endoscopic subscore (ES) ≥ 2 and a rectal bleeding (RB) subscore ≥ 1.
6. Surveillance colonoscopy (performed according to local standard) within 12 months before baseline to rule out dysplasia in participants with pancolitis > 8 years duration or participants with left sided colitis > 12 years duration. Participants without a surveillance colonoscopy within the prior 12 months will have a colonoscopy at Screening (ie, in place of Screening proctosigmoidoscopy). Any adenomatous polyps must be removed per local standard of care prior to the first dose of study drug.
7. Demonstrated inadequate response to, loss of response to, or
intolerance to at least 1 of the following therapies:
a. Conventional therapy:
i. Oral 5-aminosalicylic acid (5 ASA) compounds
ii. Corticosteroids
iii. Thiopurines (eg, azathioprine or 6 mercaptopurine)
b.Biologic therapy or JAK inhibitor therapy:
i. Anti-tumor necrosis factor alpha (TNFα) antibodies (eg, infliximab,
adalimumab, or golimumab)
ii. Anti interleukin (anti-IL)12/23 (eg, ustekinumab)
iii. Anti integrin antibodies (eg, vedolizumab)
iv. JAK inhibitors (eg, tofacitinib, upadacitinib)
8. Adequate hepatic function, defined as a total bilirubin level of ≤ 1.5 ×
upper limit of normal (ULN) and aspartate aminotransferase (AST) and
alanine aminotransferase (ALT) levels of ≤ 2.0 × ULN. Participants with
Gilbert's syndrome who have an isolated total bilirubin and normal AST
and ALT levels may participate.
9. Adequate renal function, defined as an estimated glomerular filtration
rate ≥ 60 mL/min/1.73 m2 by the Chronic Kidney Disease Epidemiology
Collaboration equation at Screening
Inclusion criteria No.: 10- 11 can be found in study protocol. |
|
| E.4 | Principal exclusion criteria |
Inflammatory Bowel Disease and Gastrointestinal Conditions
1. Severe extensive colitis as evidenced by:
a. Physician judgment that the participant is likely to require surgery (surgical intervention of any kind for UC [eg, colectomy]) within 12 weeks of baseline.
b. Current evidence of fulminant colitis or toxic megacolon, or recent history (within last 6 months) of toxic megacolon or bowel perforation.
c. Previous total colectomy.
2. Diagnosis of Crohn’s disease or indeterminate colitis or the presence or history of a fistula consistent with Crohn’s disease.
3. Diagnosis of microscopic colitis, ischemic colitis, or infectious colitis.
4. Positive assay or stool culture for pathogens (ova and parasite examination, bacteria) or positive test for Clostridium difficile at Screening. Note: Note: If C. difficile or pathogen test is positive, the subject may be treated and retested ≥ 4 weeks after completing treatment.
5. Pregnancy, lactation, or a positive serum β hCG measured during Screening.
6. Clinically relevant hematologic, hepatic, neurological, pulmonary, ophthalmological, endocrine, metabolic (including, but not limited to, hypo- and hyperkalemia), psychiatric, or other major systemic disease that will make implementation of the protocol or interpretation of the study difficult or will put the participant at risk.
7. Forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) < 70% of predicted values and FEV1/FVC ratio < 0.70 at Screening.
8. Have any of the following conditions or receiving treatments that may affect cardiovascular function:
a. Myocardial infarction, unstable angina, stroke/transient ischemic attack, decompensated heart failure requiring hospitalization, or Class III/IV heart failure within ≤ 6 months prior to or during the Screening Period.
b. Screening or prerandomization vital signs (taken in the sitting position) with a heart rate (HR) < 50 bpm OR systolic blood pressure (BP) < 90 mmHg OR diastolic BP < 55 mmHg. Vital signs may be repeated up to 3 times during a visit to confirm abnormal readings.
c. Screening or prerandomization electrocardiogram (ECG) with PR interval > 200 msec or Fridericia’s corrected QT interval (QTcF) ≥ 450 msec in men or ≥ 470 msec in women
d. History of any of the following unless treated with an implanted pacemaker or an implanted cardioverter defibrillator with pacing:
i. History or presence of recurrent symptomatic bradycardia
ii. Second or third degree atrioventricular block
iii. Periods of asystole > 3 seconds
iv. History of sick sinus syndrome or recurrent cardiogenic syncope
e. Start, stop, or change in dosage of any Class I-IV anti-arrhythmic drugs ≤ 1 week prior to dose titration starting at randomization and up to 1 week after titration to the assigned dose. This criterion also applies to the OLE Treatment Period titration: 1 week prior to and 1 week after the dose titration period.
9. Uncontrolled diabetes as determined by hemoglobin A1c (HbA1c) > 9%, or participants with diabetes with significant comorbid conditions, such as retinopathy.
10. History or presence of macular edema or retinopathy.
11. History of cancer within the last 5 years, including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin that have been excised and resolved) or precancerous conditions such as colonic mucosal dysplasia, cervical dysplasia, and cervical intraepithelial neoplasia.
12. History of lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorder, or multiple myeloma.
13. History of alcohol or drug abuse within 1 year prior to randomization.
14. Any of the following laboratory abnormalities during the Screening Period:
a. Absolute white blood cell (WBC) count < 3500/μL
b. Neutrophils < 1500/μL
c. Absolute lymphocyte count < 800/μL
d. Platelet count < 100,000/μL
e. Hemoglobin < 8 g/dL
15. Active or latent TB infection at Screening. History of untreated or inadequately treated latent
TB infection. The following are EXCEPTIONS to this exclusion criterion:
a. Participants with latent TB, who have been ruled out for active TB,
have completed an appropriate course of TB prophylaxis treatment per
national/local medical guidelines or WHO guidelines, have a chest
radiograph without changes suggestive of active TB infection, and have
not had recent close contact with a person with active TB are eligible to
enroll in the study. It is the responsibility of the Investigator to verify
the adequacy of previous TB treatment and provide appropriate
documentation of treatment compliance.
b. Participants diagnosed with latent TB at Screening, ruled out for
active TB and have received at least 4 weeks of an appropriate TB
prophylaxis regimen may be rescreened for enrollment. Participant will
complete their prophylactic regimen during the trial.
Exclusion criteria No.: 16 - 37 can be found in study protocol. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The proportion of participants with clinical remission at Week 13 using modified Mayo score (MMS). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
The proportion of participants with endoscopic improvement at Week 13.
The proportion of participants with symptomatic remission at Week 13.
The proportion of participants with histologic remission at Week 13.
The proportion of participants with endoscopic improvement-histologic
remission at Week 13.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 62 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Ukraine |
| Georgia |
| India |
| Korea, Republic of |
| United States |
| Bulgaria |
| Czechia |
| France |
| Germany |
| Hungary |
| Italy |
| Lithuania |
| Poland |
| Slovakia |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
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