Clinical Trials Register

Summary
EudraCT Number:	2019-002205-22
Sponsor's Protocol Code Number:	IM014029
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-02-11
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

Netherlands - Competent Authority

A.2

EudraCT number

2019-002205-22

A.3

Full title of the trial

"A Randomized, Placebo-Controlled, Double-Blind, Multicenter Study to Assess the Efficacy and Safety of Branebrutinib Treatment in Subjects with Active Systemic Lupus Erythematosus or Primary Sjögren’s Syndrome, or Branebrutinib Treatment Followed by Open-label Abatacept Treatment in Subjects with Active Rheumatoid Arthritis".

- SLE Sub-protocol: "Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Branebrutinib in Systemic Lupus Erythematosus."
- pSS Sub-protocol: "Placebo-Controlled, Double-Blind Study to Assess the Efficacy and Safety of Branebrutinib in Primary Sjögren’s Syndrome."
- RA Sub-protocol: "Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Branebrutinib Treatment Followed by Abatacept Treatment in Subjects with Rheumatoid Arthritis."

A.3.1

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

"Clinical research study to measure how good and how safe Branebrutinib compared to a placebo is in treating participants with Systemic Lupus Erythematosus or Primary Sjögren’s Syndrome, or participants with Rheumatoid Arthritis when being treated with Branebrutinib and methotrexate followed with Abatacept treatment."

A.4.1

Sponsor's protocol code number

IM014029

A.5.4

Other Identifiers

Name:

IND number

Number:

142401

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	Bristol-Myers Squibb International Corporation
B.1.3.4	Country	Belgium
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	Bristol-Myers Squibb Company
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bristol-Myers Squibb International Corporation
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Parc de l'Alliance - Avenue de Finlande, 4
B.5.3.2	Town/ city	Braine-l'Alleud
B.5.3.3	Post code	1420
B.5.3.4	Country	Belgium
B.5.6	E-mail	clinical.trials@bms.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	Branebrutinib
D.3.2	Product code	BMS-986195
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Branebrutinib
D.3.9.1	CAS number	1912445-55-6
D.3.9.2	Current sponsor code	BMS-986195
D.3.9.3	Other descriptive name	BMS986195
D.3.9.4	EV Substance Code	SUB181091
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	3
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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	ORENCIA 125 mg solution for injection in pre-filled syringe
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Pharma EEIG
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	Abatacept
D.3.2	Product code	BMS-188667
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	ABATACEPT
D.3.9.1	CAS number	332348-12-6
D.3.9.2	Current sponsor code	BMS-188667
D.3.9.3	Other descriptive name	ORENCIA
D.3.9.4	EV Substance Code	SUB20635
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	125
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	No
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	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

SLE Sub-protocol: Systemic Lupus Erythematosus
pSS Sub-protocol: Primary Sjögren’s Syndrome
RA Sub-protocol: Rheumatoid Arthritis

E.1.1.1

Medical condition in easily understood language

Lupus, Sjögren’s Syndrome and Arthritis are autoimmune diseases that develops when body's immune system overreacts to unknown stimulus making antibodies/proteins directed against own's body 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.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	PT
E.1.2	Classification code	10040767
E.1.2	Term	Sjogren's syndrome
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.1
E.1.2	Level	PT
E.1.2	Classification code	10039073
E.1.2	Term	Rheumatoid arthritis
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

SLE Sub-protocol:
-To compare the efficacy of branebrutinib with PBO at Week 24 in the treatment of subjects with SLE

pSS Sub-protocol:
-To compare the efficacy of branebrutinib with PBO at Week 24 in the treatment of subjects with pSS

RA Sub-protocol:
-To compare the efficacy of branebrutinib with PBO at Week 12 in the treatment of subjects with moderate to severe RA on a stable background of MTX who have had an inadequate response to MTX

E.2.2

Secondary objectives of the trial

SLE Sub-protocol:
-To compare the efficacy of branebrutinib with PBO at Week 24 in the treatment of subjects with SLE.
-To compare the efficacy of branebrutinib with PBO on measures of global and organ-specific clinical responses at Week 24 in the treatment of subjects with SLE.
- To compare the safety and tolerability of branebrutinib with PBO in subjects with SLE.

pSS Sub-protocol:
-To compare the safety and tolerability of branebrutinib with PBO in subjects with pSS.

RA Sub-protocol:
-To compare the efficacy of branebrutinib with PBO at Week 12 in the treatment of subjects with moderate to severe RA on a stable background of MTX who have had an inadequate response to MTX.
- To evaluate the safety and tolerability at Week 24 of switching at Week 12 from branebrutinib or PBO to abatacept in subjects with RA.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Sub-Protocol for Systemic Lupus Erythematosus (SLE):
- Active SLE as defined by the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) classification.
- Diagnosed with SLE more than 24 weeks before screening visit.

Sub-Protocol for primary Sjögren's Syndrome (pSS):
- Moderate to severe pSS, meeting ACR-EULAR classification criteria.

Sub-Protocol for active Rheumatoid Arthritis (RA):
- Moderate to severe adult-onset RA.
- ACR global functional status class I to III.

For all sub-studies:
- Women and men must agree to follow instructions for methods of contraception.

Please, be referred to the Protocol document for a complete list of Inclusion citeria.

E.4

Principal exclusion criteria

Sub-Protocol for Systemic Lupus Erythematosus (SLE):
- Certain other autoimmune diseases and overlap syndromes.

Sub-Protocol for primary Sjögren's Syndrome (pSS):
- Certain other immune-mediated diseases, active fibromyalgia, or other medical conditions.

Sub-Protocol for Rheumatoid Arthritis (RA):
- Diagnosis with juvenile arthritis or idiopathic arthritis before age 16.

For all sub-studies:
- History of any significant drug allergy
- Active infection, significant concurrent medical condition, or clinically significant abnormalities

Please, be referred to the Protocol document for a complete list of Exclusion citeria.

E.5 End points

E.5.1

Primary end point(s)

1. SLE: mCLASI activity score response [ Time Frame: at 24 weeks ]
Proportion of participants with a ≥ 50% reduction of mCLASI from baseline

2. pSS: Proportion of subjects with changes in a composite score that includes ESSPRI (EULAR Sjögren's Syndrome Patient Reported Index), ESSDAI (EULAR Sjögren's Syndrome Disease Activity Index), ocular staining, salivary flow and serological marker [ Time Frame: at 24 weeks ]
Clinically significant improvements from baseline in ESSPRI, ESSDAI, ocular staining, salivary flow, and serological marker (rheumatoid factor [RF], IgG, complement C3 or C4, cryoglobulin) used in the composite measure.

3. RA: ACR50 response [ Time Frame: at 12 weeks ]
Proportion of participants achieving ACR50 response (American College of Rheumatology 50 criteria)

E.5.1.1

Timepoint(s) of evaluation of this end point

SLE Sub-Protocol:
-Week 20 and Week 24
pSS Sub-Protocol:
- Week 24
RA Sub-protocol:
-Week 12

E.5.2

Secondary end point(s)

1. SLE: SLEDAI-2K score response [ Time Frame: at 24 weeks ]
Change from baseline in SLEDAI-2K score (Systemic Lupus Erythematosus Disease Activity Index 2000)

2. SLE: BILAG-based Composite Lupus Assessment response [ Time Frame: at 24 weeks ]
Change from baseline in BILAG-based (British Isles Lupus Assessment Group) Composite Lupus Assessment response

3. RA: DAS28-CRP response [ Time Frame: at 12 weeks ]
Change from baseline in DAS28-CRP (Disease Activity Score 28 - C reactive protein)

4. RA: DAS28-ESR response [ Time Frame: at 12 weeks ]
Change from baseline in DAS28-ESR (Disease Activity Score 28 - Erythrocyte Sedimentation Rate)

5. RA: SDAI response [ Time Frame: at 12 weeks ]
Change from baseline in SDAI (Simplified Disease Activity Index)

6. RA: CDAI response [ Time Frame: at 12 weeks ]
Change from baseline in CDAI (Clinical Disease Activity Index)

7. RA: ACR20 response [ Time Frame: at 12 weeks ]
Proportion of participants achieving ACR20 response (American College of Rheumatology 20 criteria)

8. RA: ACR70 response [ Time Frame: at 12 weeks ]
Proportion of participants achieving ACR70 response (American College of Rheumatology 70 criteria)

9. SLE, pSS, RA: Safety [ Time Frame: up to 28 weeks ]
Incidence of Serious Adverse Events, Adverse Events; number of clinically significant changes in lab assessment of blood, number of clinically significant changes in vital sign of body temperature, blood pressure, and respiratory rate; number of clinically significant changes in electrocardiogram.

E.5.2.1

Timepoint(s) of evaluation of this end point

SLE Sub-protocol:
-Week 24
-Week 28 (safety)

pSS Sub-protocol:
-Week 24
-Week 28 (safety)

RA Sub-protocol:
-Week 12
-Week 28 (safety)

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

Yes

E.6.11

Pharmacogenomic

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

Mexico

United States

Belgium

France

Germany

Poland

United Kingdom

Netherlands

Spain

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

SLE Sub-protocol/pSS Sub-protocol/RA Sub-protocol:
-Final date on which data for the primary endpoint was or is expected to be collected, if it is not the same.

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:

175

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

185

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)

At the end of the study, BMS will not continue to provide BMS-supplied study treatment to subjects/investigators unless BMS chooses to extend the study. The investigator should ensure that the subject receives appropriate standard of care to treat the condition under study.

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

2020-02-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-06-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-12-05

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