Clinical Trials Register

Summary
EudraCT Number:	2014-005324-10
Sponsor's Protocol Code Number:	CT-P10_3.4
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-06-18
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2014-005324-10

A.3

Full title of the trial

A Phase 3, Randomised, Parallel-Group, Active-Controlled, Double-Blind Study to Compare Efficacy and Safety between CT-P10 and Rituxan in Patients with Low Tumour Burden Follicular Lymphoma

Randomizované, aktivně kontrolované, dvojitě zaslepené klinické hodnocení fáze 3 s paralelními skupinami, srovnávající účinnost a bezpečnost přípravku CT-P10 a Rituxanu u pacientů s folikulárním lymfomem s malou nádorovou masou

A.3.1

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

A Study to Compare Efficacy and Safety between CT-P10 and Rituxan in Patients with Low Tumour Burden Follicular Lymphoma

A.4.1

Sponsor's protocol code number

CT-P10_3.4

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02260804

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	MinJi Ma- Clinical Operation
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	+8232850 6727
B.5.5	Fax number	+8232850 6739
B.5.6	E-mail	MinJi.Ma@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	No
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.3.1	Product name	CT-P10
D.3.2	Product code	CT-P10
D.3.4	Pharmaceutical form	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	RITUXIMAB
D.3.9.1	CAS number	174722-31-7
D.3.9.2	Current sponsor code	CT-P10
D.3.9.4	EV Substance Code	SUB12570MIG
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	500
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	Yes
D.3.11.13.1	Other medicinal product type	Monoclonal antibody (biosimilar).
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Rituxan
D.2.1.1.2	Name of the Marketing Authorisation holder	Biogen Idec Inc and Genentech USA Inc
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.3.1	Product name	RITUXIMAB
D.3.4	Pharmaceutical form	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	RITUXIMAB
D.3.9.1	CAS number	174722-31-7
D.3.9.4	EV Substance Code	SUB12570MIG
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	500
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	Yes
D.3.11.13.1	Other medicinal product type	Monoclonal antibody.

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Low Tumour Burden Follicular Lymphoma.

E.1.1.1

Medical condition in easily understood language

Cancer that affects a certain type of blood cell.

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10065856
E.1.2	Term	Non-Hodgkin's lymphoma unspecified histology indolent
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 that CT-P10 is similar to Rituxan in terms of efficacy as determined by overal response rate [ORR] (complete response [CR] + unconfirmed complete response [CRu] + partial response [PR]) at 7 months (Prior to Cycle 3 of Maintenance Study Period) according to the Modified Response Criteria for Malignant Lymphoma.

E.2.2

Secondary objectives of the trial

• To evaluate ORR (CR + CRu + PR) according to the Modified Response Criteria for Malignant Lymphoma during the study period.
• To evaluate additional efficacy parameters (progression-free survival, time to progression and overall survival according to the Modified Response Criteria for Malignant Lymphoma).
• To evaluate pharmacokinetics, pharmacodynamics (B-lymphocyte [B-cell] kinetics), overall safety including immunogenicity, and biomarkers of CT-P10 in comparison with Rituxan.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patient is male or female ≥18 years.
2. Patient has histologically confirmed CD20+ FL grade 1 to 3a according to the World Health Organization 2008 classification (Jaffe et al 2009); biopsy within 6 months before the first administration of the study drug.
3. Patient has at least 1 measurable tumour mass in 2 dimensions, and the mass must be:
• Nodal lesion >15 mm in the longest dimension; or
• Nodal lesion >10 mm to ≤15 mm in the longest dimension and >10 mm in the shortest dimension; or
• Extranodal lesion with both long and short dimensions ≥10 mm
4. Patient has Ann Arbor stage II, III, or IV disease.
5. Patient has low tumour burden, defined as based on Groupe d'Etudes des Lymphomes Folliculaires (GELF) criteria:
• No B symptoms,
• LDH < upper limit of normal (ULN),
• Largest nodal or extra mass <7 cm,
• <3 nodal sites with a diameter ≥3 cm,
• No significant serous effusions detectable clinically or on CT (small, clinically non-evident effusions on CT scan are not deemed significant),
• Spleen ≤16 cm by CT, and
• No clinical organ failure or organ compression (e.g. ureteric obstruction)
6. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (Oken et al 1982).
7. For both male and female patients and their partners of childbearing potential, patient agrees to practice true abstinence (when this is in line with preferred and usual lifestyle of the subject) or to use one of the following medically acceptable methods of contraception during the course of the study and for 12 months following discontinuation of study drug (excluding women who are not of childbearing potential and men who have been sterilised):
• 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 devices
Male or female patients and their partners who have been surgically sterilised for less than 6 months prior to the first administration of the study drug must agree to use 1 medically acceptable method of contraception or practice true abstinence during study treatment.
Menopausal females must have experienced their last period more than 12 months prior to study entry (ie, when the informed consent form [ICF] is signed) to be classified as not of childbearing potential.
For both premenopausal women and women who are less than or equal to 12 months after the onset of menopause, patient has a negative serum pregnancy test during the Screening Period.
8. Patient has adequate bone marrow, hepatic, and renal function reserve as evidenced by:
• Haemoglobin level of ≥10 g/dL
• Absolute neutrophil count of ≥1500/mm3
• Platelet count of ≥100 000/mm3
• Total bilirubin level of ≤2.0 mg/dL
• Aspartate aminotransferase and alanine aminotransferase levels of ≤3 times the ULN for the reference laboratory (≤5 × ULN for the reference laboratory with known hepatic involvement by lymphoma)
• A serum creatinine level of ≤1.5 × ULN for the reference laboratory, or a calculated creatinine clearance by the Cockcroft-Gault equation (Rostoker et al 2007) of ≥50 mL/min
9. Patient is able to understand verbal and/or written instructions and comply with all study requirements.
10. Patient is informed, given ample time and opportunity to read and/or understand about participation in the study, and has signed and dated the written ICF.

E.4

Principal exclusion criteria

1. Patient has received rituximab (or a rituximab proposed biosimilar product).
2. Patient has allergies or hypersensitivity to contrast agents for radiograph, murine, chimeric, human or humanised proteins.
3. Patient has evidence of histological transformation to high-grade or diffuse large B-cell lymphoma.
4. Patient has known central nervous system involvement or any evidence of spinal cord compression by lymphoma.
5. Patient has received previous treatment for NHL:
• Previous treatment including chemotherapy, radiotherapy, immunotherapy, and/or surgery (except previous biopsy).
• All doses of corticoid therapy for treatment of NHL.
• Corticoid therapy within 4 weeks before the first administration of the study drug, with prednisone >20 mg per day (or equivalent doses of other steroid medications) for any purpose except NHL.
6. Patient has a severe infection, such as sepsis, abscesses, active tuberculosis (TB), or opportunistic infections.
7. Patient has a known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C (carriers of hepatitis B and hepatitis C are not permitted to enrol into the study).
8. Patient has New York Heart Association (Raphael et al 2007) class III or IV heart failure, severe uncontrolled cardiac disease (unstable angina, clinically significant electrocardiogram [ECG] abnormalities), or myocardial infarction within the previous 6 months before the first administration of the study drug.
9. Patient has any malignancy other than NHL, except adequately treated squamous or basal cell carcinoma of the skin or cervical carcinoma in situ, within the 5 years before the first administration of the study drug.
10. Patient has a current or recent treatment (within 42 days before the first administration of the study drug or 5 times the half-life, whichever is longer, prior to screening) with any other investigational medicinal product or device.
11. Patient has uncontrolled diabetes mellitus, even after insulin treatment.
12. Patient is pregnant or lactating. Patients who are planning to be pregnant or to breastfeed before, during, or within 12 months after the last administration of the study drug are not permitted to enrol into the study.
13. Patient is taking a live, live-attenuated, or nonlive vaccine within 4 weeks before the first administration of the study drug.
14. Patient has evidence of any other coexisting disease or medical or psychological condition, metabolic dysfunction, unstable pulmonary condition, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational product, or patient is high risk for treatment complications at the investigator’s discretion.

E.5 End points

E.5.1

Primary end point(s)

Overall response rate (CR + CRu + PR) at 7 months (Prior to Cycle 3 of Maintenance Study Period), according to the Modified Response Criteria for Malignant Lymphoma.

E.5.1.1

Timepoint(s) of evaluation of this end point

At 7 months (Prior to Cycle 3 of Maintenance Study Period).

E.5.2

Secondary end point(s)

- The following efficacy parameters for the study drug will be determined as secondary endpoints:
• Overall response rate (CR + CRu + PR) during the study period according to the Modified Response Criteria for Malignant Lymphoma
• Progression-free survival, defined as the interval between randomisation and disease progression/relapse, or death from any cause, whichever occurs first
• Time to progression, defined as the interval between randomisation and disease progression/relapse or death as a result of lymphoma, whichever occurs first
• Overall survival, defined as the interval between randomisation and death from any cause
- The following pharmacokinetic (PK) parameters for the study drug will be determined as secondary endpoints:
• Maximum serum concentration (Cmax) at each dose
• Trough serum concentration (Ctrough) at each dose
- The secondary pharmacodynamic (PD) endpoint is B-cell kinetics.
- The safety endpoints will be assessed using the following: AEs, SAEs, concomitant medications, hypersensitivity (via vital signs monitoring including systolic and diastolic BP, heart rate, respiratory rate, and body temperature), physical examination findings, vital signs measurements, clinical laboratory analyses, chest x ray findings, ECG findings, infection, infusion related reactions, immunogenicity testing, immunoglobulin testing, and TB assessment.
- The biomarker endpoints: the FcγR genotype (FcγRIIa, IIIa, and/or any necessary genotypes) will be evaluated as secondary endpoints.

E.5.2.1

Timepoint(s) of evaluation of this end point

Endpoints will be assessed during the whole study till Follow-up visit (Day 1 of Cycle 1 of the Induction Study Period and Day 1 of Cycles 1-2 and Day 1 of Cycle 2-4, during Maintenance Study Period, and Follow-up Period). Please note not all endpoints will be assessed on each of the visits.

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

Yes

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Biosimilar.

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)

Yes

E.8.2.2

Placebo

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

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

Australia

Belarus

Brazil

Chile

Czech Republic

Georgia

India

Israel

Italy

Japan

Korea, Republic of

Latvia

Malaysia

Mexico

Peru

Poland

Portugal

Romania

Russian Federation

Spain

Taiwan

Thailand

Ukraine

United Kingdom

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

The end of the study is defined as the date of the database is locked

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

E.8.9.2

In all countries concerned by the trial days

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:

173

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

F.4.2.2

In the whole clinical trial

250

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)

Standard of Care

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

2015-08-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-08-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-09-04

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials