Clinical Trials Register

Summary
EudraCT Number:	2016-001966-27
Sponsor's Protocol Code Number:	AGB002
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-09-07
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

UK - MHRA

A.2

EudraCT number

2016-001966-27

A.3

Full title of the trial

A Randomized, Double-blind, Multi-center, Multi-national Trial to Evaluate the Efficacy, Safety, and Immunogenicity of SAIT101 Versus Rituximab as a First-line Immunotherapy Treatment in Patients with Low Tumor Burden Follicular Lymphoma

A.3.1

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

A Study Comparing SAIT101 to MabThera® in Patients with Low Tumor Burden Follicular Lymphoma

A.4.1

Sponsor's protocol code number

AGB002

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	Archigen Biotech Limited
B.1.3.4	Country	United Kingdom
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	Archigen Biotech Limited
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Archigen Biotech Limited
B.5.2	Functional name of contact point	Medical Inquiry Team
B.5.3	Address:
B.5.3.1	Street Address	1 Francis Crick Avenue, Cambridge Biomedical Campus
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	CB2 0AA
B.5.3.4	Country	United Kingdom
B.5.6	E-mail	medicalinquiry@archigenbio.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	SAIT101 (rituximab biosimilar)
D.3.2	Product code	SAIT101
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	SAIT101
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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	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	MabThera®
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Ltd.
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.3.1	Product name	MabThera®
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	AS2
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Low Tumor Burden Follicular Lymphoma (LTBFL)

E.1.1.1

Medical condition in easily understood language

This is a disease of the lymph tissue (part of the immune system) that affects a type of white blood cell
called B-Lymphocytes.

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	HLGT
E.1.2	Classification code	10025320
E.1.2	Term	Lymphomas non-Hodgkin's B-cell
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

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 compare the efficacy of SAIT101 with rituximab licensed in the European Union (hereafter designated MabThera®, brand name in EU) when administered as a first-line immunotherapy in patients with low tumor burden follicular lymphoma (LTBFL).

E.2.2

Secondary objectives of the trial

To evaluate SAIT101 versus MabThera® with respect to:
• Safety and tolerability;
• Immunogenicity;
• Pharmacokinetics (PK) and pharmacodynamics (PD) in a sub population of patients.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Pharmacokinetic/pharmacodynamic optional substudy for a sub-population

E.3

Principal inclusion criteria

Patients with histologically-confirmed, Ann Arbor stage II – IVA CD20+ Follicular Lymphoma (FL) (Grades 1, 2, or 3a), aged at least 18 years, not previously treated for their FL, low tumor burden according to Groupe D’Etude des Lymphomes Folliculaires (GELF) criteria, Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, at least one measurable lesion per the International Working Group (IWG) criteria 2007 at screening, no evidence of transformation to a large cell histology, and adequate hematological, renal, and liver function.

E.4

Principal exclusion criteria

1. Previous treatment with any chemotherapy and/or rituximab or other monoclonal antibody.
2. Prior radiotherapy completed <28 days before study enrollment.
3. Anticipated need for concomitant administration of any other experimental drug, or a concomitant chemotherapy, anticancer hormonal therapy, radiotherapy, or immunotherapy during study participation.
4. Concomitant disease which requires continuous therapy with corticosteroids at doses equivalent to prednisolone >20 mg/day.
5. Leukemia or transformation to diffuse large B cell lymphoma secondary to previously untreated follicular lymphoma.
6. Prior or concomitant malignancies within 5 years prior to screening, with the exceptions of non-melanoma skin cancer, adequately treated carcinoma in situ of the cervix, adequately treated breast cancer in situ, and localized prostate cancer stage T1c, provided that the patient underwent curative treatment and remains relapse free.
7. Patients with a body surface area >3.0 m2.
8. Major surgery (excluding lymph node biopsy) within 28 days prior to randomization.
9. Primary or secondary immunodeficiency (history of, or currently active), including known history of human immunodeficiency virus (HIV) infection or positive test at screening.
10. Acute, severe infection (e.g., sepsis and opportunistic infections), or active, chronic or persistent infection that might worsen with immunosuppressive treatment (e.g., herpes zoster).
11. Positive serological test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C serology.
 Patients with a negative HBsAg and positive HBcAb must have a hepatitis B virus (HBV) deoxyribonucleic acid (DNA) level <20 IU/mL (or 112 copies/mL) by polymerase chain reaction (PCR). These HBV patients must be willing to undergo PCR HBV DNA testing during treatment and may participate following consultation with a hepatitis expert regarding monitoring and use of HBV antiviral therapy, and provided they agree to receive treatment as indicated. An HBV re-test will be performed at each study visit from Week 5 onwards, and at the discretion of the Investigator.
 Patients with a positive test because of HBV vaccine may be included (i.e., anti-HBs+, anti-HBc–).
 Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV ribonucleic acid (RNA).
12. Confirmed current active tuberculosis (TB). Patients with latent TB as determined by tuberculosis skin testing (e.g. Mantoux test) or interferon-gamma release assay (IGRA e.g.QuantiFERON-TB test) may be enrolled if such patients have written confirmation from their health care provider (e.g., Pulmonologist or Infection Specialist) of adequate prophylaxis before or within the screening period, and no evidence of tuberculosis on a chest X-ray performed within 3 months of Day 1 or chest CT.
13. Central nervous system (CNS) or meningeal involvement, or cord compression by the lymphoma; history of CNS lymphoma. A brain (CT or MRI) scan should be conducted at screening ONLY if lesions are suspected on the brain, to exclude patients with brain localization of FL.
14. History of a severe allergic reaction or anaphylactic reaction to a biological agent or history of hypersensitivity to any component of the trial drug (e.g., hypersensitivity or allergy to murine products).
15. Patients who have significant cardiac disease, including but not limited to history of congestive heart failure (New York Heart Association Class III/IV; see Appendix 7), unstable angina, or uncontrolled cardiac arrhythmia.
16. Uncontrolled or severe hypertension, or cerebrovascular disease.
17. Serious underlying medical conditions that, per the Investigator’s discretion, could impair the ability of the patient to participate in the trial (including but not limited to ongoing active infection, severe immunosuppression, uncontrolled diabetes mellitus, gastric ulcers, or active autoimmune disease).
18. Any other co-existing medical or psychological condition(s) that will preclude participation in the study or compromise ability to give informed consent and/or comply with study procedures.
19. Treatment with any investigational medicinal product (IMP) within 4 weeks prior to initiation of 1st infusion of study drug, or treatment with a drug that has not received regulatory approval for any indication within 4 weeks or a minimum of 5 half-lives, whichever is longer, of the 1st infusion of study drug.
20. Receipt of a live/attenuated vaccine within 6 weeks prior to the screening visit.
21. Females who are pregnant, breastfeeding, or planning a pregnancy during the treatment period or within 12 months after the last infusion of study drug.
22. Patients who are investigational site staff members involved in the conduct of the trial, and their family members, site staff members otherwise supervised by the investigator, or patients who are Archigen employees directly involved in the conduct of the trial.

E.5 End points

E.5.1

Primary end point(s)

Primary Efficacy Endpoint:
Overall Response Rate (ORR) (Complete Response [CR] + Partial Response [PR]) at Week 28 as defined by IWG criteria 2007

E.5.1.1

Timepoint(s) of evaluation of this end point

at Week 28 as defined by IWG criteria 2007

E.5.2

Secondary end point(s)

Secondary Efficacy Endpoints:
- Tumor response evaluations as defined by the revised IWG Criteria 2007, for malignant lymphoma:
 Overall Response Rate (ORR)
 Complete Response (CR)
 Partial Response (PR)
 Stable Disease (SD)
 Progressive disease (PD)
 Time to event (TTE), defined as the time from the date of randomization to the date when an event occurs; an event is disease progression, death due to any cause, or the start of new treatment for FL, whichever comes first
- drug concentration,
- CD19 + B-cell count and
- immunogenicity.

E.5.2.1

Timepoint(s) of evaluation of this end point

For assessment of ORR + CR + PR + SD + PD = weeks 12 and 28 + unscheduled visit as per table 1 (CT scan)
For TTE, it is at any time or visits (from weeks 1/2/3/4/5/12/20/28/36/52) or at any unscheduled visit
For drug concentration (PK) = weeks 1/2/3/4/5/12/20/28 + unscheduled visit
For CD19 + B-cell count (hematology) = weeks 1/2/3/4/5/12/20/28/36/52 + unscheduled visit
For immunogenicity = weeks 1/2/3/4/5/12/20/28/36/52 + unscheduled visit

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

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity

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

Bosnia and Herzegovina

Brazil

Bulgaria

Chile

Croatia

Czech Republic

Egypt

France

Georgia

Germany

Hong Kong

Hungary

India

Italy

Korea, Republic of

Latvia

Mexico

Philippines

Romania

Russian Federation

Saudi Arabia

Serbia

South Africa

Spain

Thailand

Turkey

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 last visit of the last patient undergoing the study'.

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