Clinical Trials Register

Summary
EudraCT Number:	2022-002690-29
Sponsor's Protocol Code Number:	CVAY736F12302
National Competent Authority:	Romania - National Agency for Medicines and Medical Devices
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2024-10-08
Trial 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

Romania - National Agency for Medicines and Medical Devices

A.2

EudraCT number

2022-002690-29

A.3

Full title of the trial

A randomized, double-blind, placebo-controlled multicenter phase 3 study to evaluate efficacy, safety and tolerability of ianalumab on top of standard-of-care therapy in patients with systemic lupus erythematosus (SIRIUS-SLE 2)

A.3.1

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

Phase 3 study to evaluate ianalumab on top of standard-of-care therapy in patients with systemic lupus erythematosus (SIRIUS-SLE 2)

A.3.2

Name or abbreviated title of the trial where available

SIRIUS-SLE 2

A.4.1

Sponsor's protocol code number

CVAY736F12302

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT05624749

A.5.4

Other Identifiers

Name:

2023-508499-12

Number:

EU CT

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	Novartis Pharma AG
B.1.3.4	Country	Switzerland
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	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma Services Romania S.R.L.
B.5.2	Functional name of contact point	Radu Boroghina - TMO Head Romania
B.5.3	Address:
B.5.3.1	Street Address	2 Gara Herastrau St., Equilibrium Complex, Buliding 1, Floor 10, Section E10.02, District 2
B.5.3.2	Town/ city	Bucharest
B.5.3.3	Post code	020334
B.5.3.4	Country	Romania
B.5.4	Telephone number	+40 21 3129901
B.5.5	Fax number	+40 21 3129907
B.5.6	E-mail	radu_dan.boroghina@novartis.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	ianalumab
D.3.2	Product code	VAY736
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	IANALUMAB
D.3.9.1	CAS number	1929549-92-7
D.3.9.2	Current sponsor code	VAY736
D.3.9.3	Other descriptive name	VAY736
D.3.9.4	EV Substance Code	SUB193896
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	150
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	Yes
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

Systemic Lupus Erythematosus

E.1.1.1

Medical condition in easily understood language

An inflammatory disease caused when the immune system attacks its own tissues.

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10042945
E.1.2	Term	Systemic lupus erythematosus
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue 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 demonstrate superiority of subcutaneous (s.c.) ianalumab 300 mg monthly, compared to placebo, in achieving Systemic Lupus Erythematosus Responder Index (SRI-4) at Week 60

E.2.2

Secondary objectives of the trial

To demonstrate superiority of s.c. ianalumab 300 mg monthly compared to placebo in: Reducing moderate or severe British Isles Lupus Assessment Group flares up to Week(Wk) 60; Maintaining corticosteroid dose ≤5 mg/day or ≤baseline dose, whichever is lower, b/w Wk 36 & Wk 60; Achieving British Isles Lupus Assessment Group-based Composite Lupus Assessment at Wk 60; Achieving Lupus Low Disease Activity State at Wk 60; Time to first occurrence of SRI-4 from baseline up to Wk 60; Achieving SRI-4 at Wk 60 while maintaining reduced corticosteroid dose ≤5 mg/day or ≤baseline dose, whichever is lower, b/w Wk 36 & Wk 60; Achieving SRI-6 at Wk 60; Achieving Short form 36
(SF-26) Bodily Pain response at Week 60

To evaluate safety & tolerability of ianalumab 300 mg s.c. monthly

To evaluate immunogenicity of ianalumab 300 mg s.c. monthly

To characterize the PK of ianalumab 300 mg s.c monthly

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Male and Female participants aged 12 years or older at the time of screening, or limited to 18 years or older in European Economic Area countries and other countries where inclusion of participants below 18 years is not allowed.

Diagnosis of systemic lupus erythematosus (SLE) meeting the EULAR/ACR SLE classification criteria at least 6 months prior to screening

Elevated serum titers at screening of Antinuclear Antibodies (≥1:80) as determined by a central laboratory with a SLE typical fluorescence pattern.

Currently receiving corticosteroids and/or anti-malarial treatment and/or another Disease-modifying antirheumatic drug (DMARD) as specified in the protocol.

SLEDAI-2K Criteria at screening: SLEDAI-2K score ≥6 points, excluding points attributed to “fever”, “lupus headache”, "alopecia", and “organic brain syndrome”
British Isles Lupus Assessment Group-2004 disease activity level at screening of at least 1 of the following:
British Isles Lupus Assessment Group-2004 level A disease in ≥1 organ system,
Or
British Isles Lupus Assessment Group-2004 level B disease in ≥2 organ systems

Weigh at least 35 kg at screening

E.4

Principal exclusion criteria

Prior treatment with Ianalumab

History of receiving following treatment I) high dose corticosteroids, calcineurin inhibitors, JAK or other kinase inhibitors or other DMARD (except as listed in inclusion criteria) 12 weeks prior to screening II) Cyclophosphamide or biologics such as immunoglobulins (i.v. or s.c.), plasmapheresis, anti-type I interferon receptor biologic agents, anti-CD40 agents, CTLA4-Fc Ig or B-cell activating factor-targeting agents administered within 24 weeks prior to screening; belimumab administered within 12 weeks prior to screening. III) Any B-cell depleting therapies, other than ianalumab administered within 36 weeks prior to randomization or as long as B cell count is less than the lower limit of normal or baseline value prior to receipt of B cell-depleting therapy (whichever is lower). IV) Traditional Chinese medicines administered within 30 days prior to randomization

Active viral, bacterial or other infections requiring intravenous or
intramuscular treatment for clinically significant infection

Chronic infection with hepatitis B (HBV) or hepatitis C (HCV)

Evidence of active tuberculosis infection

History of primary or secondary immunodeficiency, including a positive human immunodeficiency virus (HIV) test result at screening

Any one of the following laboratory values prior to randomization
Platelets <25000/mm^3 (<25 x 10^3/μL)
Hemoglobin (Hgb) <8.0 g/dL (<5 mmol/L), or <7.0 g/dL (<4.3 mmol/L) if related to participant's SLE such as in active hemolytic anemia
Absolute neutrophil count (ANC) (<0.8 x 10^3/ μL)

Severe organ dysfunction or life-threatening disease at screening

History of major organ, hematopoietic stem cell or bone marrow transplant

Presence of severe lupus kidney disease as defined by proteinuria above 2g/day or equivalent using spot urine protein creatinine ratio

Receipt of live/attenuated vaccine within a 4-week period before first dosing

Any uncontrolled, co-existing serious disease, which in the opinion of the investigator will place the participant at risk for participation or interfere with evaluation for SLE-related symptoms

History of hypersensitivity to drugs of similar chemical class (e.g., IgG1 biologics) or oral
CS or to any of the constituents of the study drugs (sucrose, L-histidine hydrochloride, Lhistidine,
polysorbate 20)

History of non-compliance with medical regimens or considered potentially unreliable

Use of other investigational drugs within 5 half-lives of enrollment or within 30 days or
until the expected pharmacodynamic effect has returned to baseline, whichever is longer,
or longer if required by local regulations

Non-lupus conditions such as asthma, gout or urticaria, requiring intermittent or chronic treatment with systemic corticosteroids

History of malignancy of any organ system other than localized basal cell carcinoma of the skin or in situ cervical cancer

Pregnant or nursing (lactating) women.

Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while on study treatment and for 6 months after stopping of investigational drug.

US (and other countries, if locally required): sexually active males unless using barrier protection during intercourse while taking study treatment

Any surgical, medical, psychiatric or additional physical condition that may jeopardize participation in this study

E.5 End points

E.5.1

Primary end point(s)

Proportion of participants achieving SRI-4 at Week 60

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 60

E.5.2

Secondary end point(s)

1. Proportion of participants with no moderate or severe British Isles Lupus Assessment Group flare up to Week 60

2. Proportion of participants maintaining between Week 36 and Week 60 a reduced corticosteroid dose of predniso(lo)ne ≤5 mg/day or ≤baseline dose, whichever is lower.

3. Proportion of participants achieving British Isles Lupus Assessment Group-based Composite Lupus Assessment at Week 60

4. Proportion of participants achieving Lupus Low Disease Activity State at Week 60

5. Time to first occurrence of SRI-4 from baseline to Week 60
6. Proportion of participants achieving SRI-4 at Week 60 while maintaining between Week 36 and Week 60 a reduced corticosteroid dose of predniso(lo)ne ≤5 mg/day or ≤baseline dose, whichever is lower
7. Proportion of participants achieving SRI-6 at Week 60
8. Proportion of participants achieving SF-36 Bodily Pain response at
Week 60

9. Proportion of participants with AEs and SAEs

10. Clinical laboratory measurements

11. Vital Signs

12. Incidence and titer of anti-ianalumab antibodies in serum (ADA assay) over time

13. Ianalumab concentration in serum during the treatment and follow-up (up to the end of study)

E.5.2.1

Timepoint(s) of evaluation of this end point

1,3,4,6,7 - Week 60

2 - Between Week 36 and Week 60

5 - from baseline to Week 60

8 - Week 60

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

Yes

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

Tolerability

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

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

Argentina

Chile

Colombia

Taiwan

Australia

India

Korea, Republic of

Mexico

United Kingdom

United States

France

Germany

Italy

Romania

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

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

224

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

280

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)

Up to 2 year safety follow-up: Patients will be followed for at least 20 weeks (mandatory follow-up) or longer (conditional follow-up), until B cell recovery or up to 2 years after the end of treatment (EOT visit). In addition, the Investigator must provide follow-up medical care for all subjects, including subjects who are prematurely withdrawn from the study, or must refer them for appropriate ongoing care.
Extension trial to be offered to patients VAY736F12301E1

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

2022-12-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-03-09

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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