E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to Severely Active Ulcerative Colitis |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 100000004856 |
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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 |
To demonstrate superiority of CT-P13 SC over Placebo SC based on clinical remission at Week 54 |
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E.2.2 | Secondary objectives of the trial |
To evaluate additional efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and overall safety including immunogenicity |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Patient is male or female aged 18 to 75 years, inclusive.
-Patient has moderately to severely active UC with a modified Mayo score of 5 to 9 points with endoscopic subscore of ≥ 2 points at Screening.
-Patient with UC, confirmed by endoscopic or radiographic and histological criteria. Histopathology report supporting the diagnosis must be available in the source documents prior to the first administration of the study drug (Day 0).
-Patient who has been treated for active UC but has not responded despite conventional therapy including corticosteroids alone or in combination with 6-mercaptopurine (6-MP) or azathioprine or who is intolerant to or has medical contraindications to such therapies.
-Patient who is receiving stable doses of the following UC treatments or currently not receiving UC
treatment during specified time frame:
*Azathioprine, or 6-MP, or methotrexate for at least 8 weeks prior to the first administration of the
study drug (Day 0)
*Oral corticosteroids at the equivalent dose of 20 mg/day or less of prednisone for at least 2 weeks
prior to the first administration of the study drug (Day 0)
*Oral budesonide at the dose of 9 mg/day or less at least for 2 weeks prior to the first administration
of the study drug (Day 0)
*Oral 5-ASA for at least 4 weeks prior to the first administration of the study drug (Day 0)
*Antibiotics (e.g., ciprofloxacin, metronidazole) for at least 4 weeks prior to the first administration
of the study drug (Day 0). Patient who has adequate renal and hepatic function at Screening as defined by the following clinical chemistry results:
*Serum creatinine < 1.5×upper limit of normal (ULN) or an estimated creatinine clearance level
> 50 mL/min (by Cockcroft-Gault formula).
*Serum alanine aminotransferase < 2.5×ULN
*Serum aspartate aminotransferase < 2.5×ULN
*Serum total bilirubin < 2×ULN
-Patient who has the following clinical hematology results at Screening:
*Hemoglobin ≥ 8.5 g/dL (SI [Système International d'Unités] units: ≥ 85 g/L or 5.28 mmol/L)
*White blood cell count ≥ 3.5×10 3 cells/µL (SI units: ≥ 3.5×10 9 cells/L)
*Neutrophil count ≥ 1.5×10 3 cells/µL (SI units: ≥ 1.5×10 9 cells/L)
*Platelet count ≥ 100×10 3 cells/µL (SI units: ≥ 100×10 9 cells/L)
-Patient (or legal guardian, if applicable) who is informed of the full nature and purpose of the study,
including possible risks and side effects, has the ability to cooperate with the investigator and is given
ample time and opportunity to read or understand verbal and/or written instructions, and has signed and dated the written informed consent form with date prior to participation in the study.
-For both male and female patients, the patient and his or her partner of childbearing potential who agree to use one of the following medically acceptable methods of contraception during the course of the study and for 6 months following discontinuation of study drug (excluding women who are not of childbearing potential and men who have been sterilized):
*Barrier contraceptives (male condom, female condom, or diaphragm with a spermicidal gel)
*Hormonal contraceptives (implants, injectables, combination oral contraceptives, transdermal
patches, or contraceptive rings)
*Intrauterine device
Male and female patients and their partners who have been surgically sterilized for less than 6 months prior to the date of informed consent must agree to use any of medically acceptable methods of contraception. Menopausal females must have experienced their last period more than 12 months prior to the date of informed consent to be classified as not of childbearing potential. |
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E.4 | Principal exclusion criteria |
-Patient who has previously received 2 or more biologic agents, 2 or more JAK inhibitors or 2 or more both biologic agents and JAK inhibitors
-Patient who has previously received either TNFα inhibitor or biologic agent within 5 half-lives prior to the 1st administration of the IP (Day 0)
-Patient who has previously demonstrated inadequate response or intolerance to TNFα inhibitors
-Patient who has previously received infliximab
-Patient who has allergies to any of the excipients of infliximab or any other murine and/or human proteins or has a hypersensitivity to immunoglobulin products
-Patient who has received or has a plan to receive: parenteral corticosteroids for the treatment of UC within 2 wks prior to the 1st administration of IP, rectally administered medications containing corticosteroids or 5-ASA for the treatment of UC within 2 wks prior to the 1st administration of the IP, JAK inhibitors including within 4 wks prior to the 1st administration of IP, alkylating agents within 12 mths prior to the 1st administration of IP, cyclosporine, tacrolimus, sirolimus or mycophenolate mofetil within 8 wks prior to the 1st administration of IP, live or live-attenuated vaccine within 4 wks prior to the 1st administration of IP, abdominal surgery within 6 mths prior to the 1st administration of IP, nonautologous stem cell therapy within 12 mths prior to the 1st administration of IP, apheresis for the treatment of UC within 3 wks prior to the 1st administration of IP, total parenteral nutrition within a month prior to the 1st administration of IP, exclusive enteral nutrition for more than 3 consecutive days within a month or any single day of exclusive enteral nutrition within 2 wks prior to the 1st administration of IP
-Patient who has a current or history infections: hepatitis B or hepatitis C (active or carrier state) or infection with HIV), acute infection requiring oral antibiotics within 2 wks or parenteral injection of antibiotics within 4 wks prior to the 1st administration of IP, other serious infection within 6 mths prior to the 1st administration of IP, other chronic or recurrent infection within 6 wks prior to the 1st
administration of IP, past or current granulomatous infections or opportunistic infections or invasive fungal infection, infection with Clostridium difficile toxin within 3 mths prior to the 1st administration
of IP, positive stool examinations for enteric pathogens, pathogenic ova or parasites
-Patient who has a medical condition including 1 or more of the following:
*Ulcerative colitis limited to only the rectum or to less than 15 cm of the colon
*Evidence of toxic megacolon
*Diagnosed with Crohn’s Disease or indeterminate colitis
*Extensive colonic resection prior to the first administration of IP
*Evidence of fixed symptomatic stenosis or obstruction of the large intestine
*Evidence of colonic mucosal dysplasia or adenomatous polyps.
*Currently require or are anticipated to require surgical intervention for UC during the study
*Stoma (e.g., ileostomy or colostomy) within 6 months prior to the first administration of the study
drug (Day 0)
*Body mass index ≥ 35 kg/m 2
*Uncontrolled diabetes mellitus, even after insulin treatment
*Uncontrolled hypertension (as defined by systolic blood pressure ≥ 160 mmHg or diastolic blood
pressure ≥ 100 mmHg)
*A known malignancy within 5 years prior to the first administration of the study drug (Day 0), except completely excised and cured squamous carcinoma in situ of the uterine cervix, cutaneous basal cell carcinoma, or cutaneous squamous cell carcinoma
*History of lymphoma, lymphoproliferative disease, or bone marrow hyperplasia
*NYHA class III or IV heart failure, severe uncontrolled cardiac disease or myocardial nfarction within 6 mths prior to the first administration of the IP
*History of organ transplantation
*Significant respiratory disease
*Demyelinating disorders, including multiple sclerosis nd Guillain Barré syndrome
*Any conditions significantly affecting the nervous system
-Patient who has had treatment with any other investigational device or medical product within 4 wks prior to the first administration of IP or 5 half-lives, whichever is longer.
-Female who is currently pregnant, breastfeeding or planning to become pregnant or breastfeed within 6 mhs of the last dose of IP
-Tuberculosis Exclusion Criteria - for these Exclusion Criteria please refer to the Protocol, due to the space restrictions in EudraCT form
-For the full list of the Exclusion Criteria, please refer to the protocol due to the space restrictions in EudraCT form |
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical remission at Week 54, defined as the following modified Mayo score:
(1) Stool frequency subscore of 0 or 1 point, and
(2) Rectal bleeding subscore of 0 point, and
(3) Endoscopic subscore of 0 or 1 point |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Key Secondary endpoints:
- Clinical response at Week 54, defined as a decrease in modified Mayo score from baseline of at least 2 points and at least 30%, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1 point
- Mucosal healing at Week 54, defined as an absolute endoscopic subscore of 0 or 1 point from modified Mayo score and an absolute Robarts Histopathology Index (RHI) score of 3 points or less with an accompanying laminal propria neutrophils and neutrophils in epithelium subscore of 0 point
- Corticosteroid-free remission at Week 54, defined as being in clinical remission by modified Mayo score in addition to not requiring any treatment with corticosteroid for at least 8 weeks at Week 54,
among the patients who used oral corticosteroids at baseline |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Key secondary endpoints evaluations will be conducted at Week 54. |
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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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 2 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 104 |
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 |
Austria |
Belarus |
Brazil |
Bulgaria |
Chile |
Croatia |
Czech Republic |
France |
Germany |
Greece |
Hungary |
Ireland |
Israel |
Italy |
Latvia |
Mexico |
Moldova, Republic of |
Peru |
Poland |
Russian Federation |
Serbia |
Slovakia |
South Africa |
Spain |
Turkey |
Ukraine |
United States |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |