Clinical Trials Register

Summary
EudraCT Number:	2019-003849-15
Sponsor's Protocol Code Number:	CT-P13_3.7
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-02-03
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2019-003849-15

A.3

Full title of the trial

A Randomized, Placebo Controlled, Double-Blind, Phase 3 Study to Evaluate the Efficacy and Safety of the Subcutaneous Injection of CT-P13 (CT-P13 SC) as Maintenance Therapy in Patients with Moderately to Severely Active Ulcerative Colitis

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Evaluating efficacy and safety of subcutaneous CT-P13 (CT-P13 SC) as
maintenance therapy in patients with Ulcerative Colitis

A.4.1

Sponsor's protocol code number

CT-P13_3.7

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Celltrion, Inc.
B.1.3.4	Country	Korea, Republic of
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Celltrion, Inc.
B.4.2	Country	Korea, Republic of
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Celltrion, Inc.
B.5.2	Functional name of contact point	Sung Hyun Kim
B.5.3	Address:
B.5.3.1	Street Address	23 Academy-ro
B.5.3.2	Town/ city	Yeonsu-gu, Incheon
B.5.3.3	Post code	22014
B.5.3.4	Country	Korea, Republic of
B.5.4	Telephone number	82328505778
B.5.5	Fax number	82328371203
B.5.6	E-mail	sunghyun.kim@celltrion.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Remsima
D.2.1.1.2	Name of the Marketing Authorisation holder	Celltrion Healthcare Hungary Kft.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	Remsima (CT-P13)
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INFLIXIMAB
D.3.9.1	CAS number	170277-31-3
D.3.9.2	Current sponsor code	CT-P13
D.3.9.4	EV Substance Code	SUB02681MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	120
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Inflectra
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	CT-P13
D.3.4	Pharmaceutical form	Powder for concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INFLIXIMAB
D.3.9.1	CAS number	170277-31-3
D.3.9.2	Current sponsor code	CT-P13
D.3.9.4	EV Substance Code	SUB02681MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection in pre-filled syringe
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

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

Ulcerative Colitis

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

E.1.3

Condition being studied is a rare disease

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

E.2.2

Secondary objectives of the trial

To evaluate additional efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and overall safety including immunogenicity

E.2.3

Trial contains a sub-study

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.

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

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

E.5.1.1

Timepoint(s) of evaluation of this end point

at Week 54

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

E.5.2.1

Timepoint(s) of evaluation of this end point

Key secondary endpoints evaluations will be conducted at Week 54.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

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

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

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

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

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

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

585

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

474

F.4.2.2

In the whole clinical trial

615

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients will transit to local standard of care treatment if required in the opinion of the investigator.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-04-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-02

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-07-11

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IMP with orphan designation in the indication
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