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.

pSS/RA/SLE: Animal and human studies have shown that Branebrutinib was safe and
well tolerated and may be useful to treat the signs and symptoms of pSS/RA/SLE.
Branebrutinib is an investigational drug. Investigational means that the drug
has not been approved by the regulatory authorities in the country in which the
use occurs.

RA: Abatacept is a biologic compound (modified antibody) that interferes with
the immune activity of T cells in the patient's blood. This drug is approved by
Health Authorities (FDA and EMA) for the treatment of subjects with moderate to
severe RA.

pSS: • To compare the efficacy of branebrutinib with PBO at Week 24 in the
treatment of subjects with pSS
• To compare the safety and tolerability of branebrutinib with PBO in subjects
with pSS

RA: • 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 efficacy at Week 24 of switching from branebrutinib or PBO to
abatacept at Week 12 in the treatment of subjects with moderate to severe RA

SLE: • To compare the efficacy of branebrutinib with PBO 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: • This is a double-blind, PBO-controlled Phase 2a study sub-protocol to
evaluate the effect of branebrutinib (BMS 986195) in subjects with pSS. All
subjects will receive background therapy for their primary disease as
appropriate.
• Subjects will receive double-blind oral (PO) branebrutinib 9 mg or PBO
treatment once daily for 24 weeks (Week 0 to Week 24).
• Treatment assignment will be conducted by randomization. Subjects will
undergo screening evaluations to determine eligibility within 28 days prior to
administration of study medication. Following the screening process, if
eligible for study participation, subjects will be randomized to receive
branebrutinib or PBO treatment in a 2:1 ratio. Randomization will be stratified
by hydroxychloroquine (HCQ) use (yes/no).


RA: • This is a double-blind, PBO-controlled Phase 2a study sub-protocol to
evaluate the effect of branebrutinib (BMS 986195) in subjects with RA. All
subjects will receive background therapy for their primary disease as
appropriate.
• Subjects will receive double-blind branebrutinib 9 mg administered orally
(PO) once daily (QD) or branebrutinib PBO for 12 weeks (Week 0 to Week 12).
Note: the last day of dosing of branebrutinib or PBO in the RA sub-protocol
should be the day prior to the Week 12/Day 85 visit.
• All subjects will receive an additional 12 weeks of treatment (Week 12 to
Week 24) with open-label abatacept.
• Treatment assignment will be randomized. Subjects will undergo screening
evaluations to determine eligibility within 28 days prior to administration of
study medication. Following the screening process, if eligible for study
participation, subjects will be randomized in the study to the RA sub-protocol
in a 3:1 ratio for study treatment and PBO. No stratification will be imposed
at randomization in this sub-protocol.


SLE: • This is a double-blind, PBO-controlled Phase 2a sub-protocol to evaluate
the effect of branebrutinib (BMS-986195) in subjects with active SLE. All
subjects will continue background therapy for their primary disease within
protocol-defined limits.
• Subjects will receive double-blind branebrutinib 9 mg or PBO treatment
administered orally (PO) once daily (QD) for 24 weeks (Week 0 to Week 24).
• Treatment assignment will be conducted by randomization. Subjects will
undergo screening evaluations to determine eligibility within 28 days prior to
administration of study medication. Following the screening process, if
eligible for study participation, subjects will be randomized in the SLE
sub-protocol to receive branebrutinib or PBO treatment in a 3:1 ratio.
Randomization will be stratified by immunosuppressant use (yes/no).

pSS Sub-protocol Duration:
The total duration of participation in the pSS sub-protocol is approximately 32
weeks and will be divided into the following periods: screening (up to 4
weeks), double-blind PBO-controlled treatment for 24 weeks (Week 0 to Week 24),
and follow-up (4 weeks).

Treatment Period (V2 to V9)
We will treat the patient with study medicines for 24 weeks. Neither the
patient nor the investigator will know which group the patient is in. This can
be found out if important for the patient's health.
During the treatment period the patient will be asked to come back for the
further visits and will have some further procedures and tests (including
taking blood and urine samples).

Visits and tests
This study requires that the patient will visit the hospital 8 times over a
period of 24 weeks. A visit will take approximately 2-7 hours depending on
activities scheduled. Many of the tests completed during the Screening will be
repeated during the Treatment period.



RA Sub-protocol Duration:
The total duration of participation in the RA sub-protocol is approximately 32
weeks and will be divided into the following periods: screening (up to 4
weeks), double-blind, PBO-controlled branebrutinib treatment for 12 weeks (Week
0 to Week 12), open-label treatment with abatacept for an additional 12 weeks
(Week 12 to Week 24), and follow-up (4 weeks).

Treatment Period (V2 to V10)
We will treat the patient with study medicines for 24 weeks.
There are 9 visits during the treatment period and many of the screening tests
will be repeated. The first treatment visit is visit 2. Each visit will last
approximately 2-7 h depending on the activities scheduled .Neither the patient
nor the investigator will know which group the patient is in. This can be found
out if important for the patient's health.

Visits and tests
This study requires that the patient will visit the hospital 9 times over a
period of 24 weeks. A visit will take approximately 2-7 hours depending on
activities scheduled.




SLE Sub-protocol Duration:
The total duration of participation in the SLE sub-protocol is approximately 32
weeks and will be divided into the following periods: screening (up to 4
weeks), double-blind PBO-controlled treatment for 24 weeks (Week 0 to Week 24),
and follow-up (4 weeks).

Treatment Period (V2 to V10)
We will treat the patient with study medicines for 24 weeks. Neither the
patient nor the investigator will know which group the patient is in. This can
be found out if important for the patient's health.
During the treatment period the patient will be asked to come back for the
further visits and will have some further procedures and tests (including
taking blood and urine samples).

Visits and tests
This study requires that the patient will visit the [hospital 8 times over a
period of 24 weeks. A visit will take approximately 2-7 hours depending on
activities scheduled. Many of the tests completed during the Screening will be
repeated during the Treatment period.

Participation in the study also means:
- additional time;
- additional or longer hospital stays;
- additional tests;
- instructions the patient needs to follow.


risks pSS:
Some procedures that will be done during the study may carry some risks, these
are given below, and the study doctor can provide more information to the
patient.

Blood Sample
Blood samples will be collected during this study. A needle is inserted into a
vein in the patient's arm and a small blood sample is withdrawn. Although one
needle insertion for blood draw is usually sufficient, a second one may be
necessary if the first is not successful. Collecting blood samples may cause
fainting and some pain and/or bruising at the site on the patient's arm where
the blood was taken. In rare occasions, infection may occur.

ECG
ECG will be performed, which is a process of recording the electrical activity
of the heart over a short period of time using sticky pads placed on the skin
to measure the rate and rhythm of the patient's heartbeats. The sticky pads may
cause mild skin irritation.

X-ray
The patient may receive an X-ray as part of the study. An X-ray is a form of
radiation. The radiation the patient receives from the X-ray is minimal.
However, the more radiation the patient receives over the course of life
increases the risk of cell changes in the body or having cancerous tumors. The
radiation from this study is not expected to greatly increase these risks, but
the exact increase of such risks is unknown.

Fasting Blood Sample
The patient will be asked to fast for 8-10 hours prior to some study visits
which may cause dizziness, low blood sugar and in rare occasions, fainting.

Collection of saliva for stimulated salivary flow
The patient may experience nausea while chewing to stimulate saliva production.

Eye assessments for dryness
The patient may experience some discomfort or irritation during the Schirmer*s
test while the paper strips are resting in the eyelids. The patient may also
experience some mild eye irritation from the dyes that are used for the ocular
surface staining and tear break-up time tests. The patient may have some
residual staining (depending on the dye used) of the eyes for a few hours after
these procedures. Lastly, the bright light used in the slit lamp to examine the
patient's eyes may cause some discomfort.
*
Biopsy (for optional sub study only)
If the patient accepts to take part on the optional sub study, the patient will
be requested for a labial salivary gland or parotid gland biopsy. There is a
risk of some pain, discomfort or infection associated to this procedure, since
an incision in the mucosa of the lower lip through the epithelium is
performed. Bleeding, bruising or swelling could also occur.

Lip salivary biopsy: the patient may experience some soreness at the site of
the lip salivary gland biopsy for a few days after the procedure. A small
percentage of participants may also experience numbness at the site of the
biopsy, and in rare cases the numbness may be permanent. A small scar may form
at the site which may also remain numb.
Parotid gland biopsy: the patient may experience some soreness at the site of
the incision and some temporary numbness at the site. A small scar may form at
the incision site.


General care measures are recommended as standard treatment for subjects with
pSS, unless otherwise informed by the patient's doctor, e.g. to treat a side
effect. These general care measures include: use of artificial tears (eye
drops) for dry eyes, stimulating saliva by sucking on sugarless candy to
improve dry mouth, preventing cavities by brushing and flossing after eating
meals, use petroleum for dry lips, frequent and liberal use of a moisturizing
cream or ointment to improve dry skin or the use of vaginal moisturizers or
estrogen cream to treat vaginal dryness, especially after menopause and other
similar measures.

There may be risks or side effects related to the study drug or other study
procedures that are unknown at this time. Let the study doctor know if the
patient experiences any side effects, even those which are not mentioned in
this Information sheet. The study doctor will inform the patient (or the
legally authorized representative) if new information on the study medication
becomes available that may affect the patient's decision to continue to take
part in the study



RA risks:
Some procedures that will be done during the study may carry some risks, these
are given below, and the patient's study doctor can provide more information to
the patient.

Blood Sample
Blood samples will be collected during this study. A needle is inserted into a
vein in the patient's arm and a small blood sample is withdrawn. Although one
needle insertion for blood draw is usually sufficient, a second one may be
necessary if the first is not successful. Collecting blood samples may cause
fainting and some pain and/or bruising at the site on the patient's arm where
the blood was taken. In rare occasions, infection may occur.

ECG
ECG will be performed, which is a process of recording the electrical activity
of the heart over a short period of time using sticky pads placed on the skin
to measure the rate and rhythm of the patient's heartbeats. The sticky pads may
cause mild skin irritation.

MRI Scan with gadolinium contrast
MRI is a non-invasive (not entering or penetrating the body or body tissue)
imaging test that uses a magnetic field and pulses of radio wave energy to take
pictures of organs and structures inside the body. The patient will need to lay
flat in a special machine that contains a magnet. People who are claustrophobic
(feel uncomfortable in confined spaces) may feel uncomfortable inside the MRI
machine. If the patient feels uncomfortable in confined spaces, please tell the
study doctor. The patient can request that the MRI be stopped at any time, but
the scan may not be complete.
As part of the MRI scan, the patient will receive an intravenous injection of
gadolinium, a contrast agent. This injection increases the accuracy of the
scan. Gadolinium contrast has been used safely in many cases, but minor
reactions such as headache, nausea, or itchiness occur in about 2% of subjects,
and very rare severe reactions, including severe allergic reactions occur in
less than one in 40,000 subjects. The patient will be monitored for any signs
or symptoms of gadolinium reaction.

X-ray
The patient may receive an X-ray as part of the study. An X-ray is a form of
radiation. The radiation the patient receives from the X-ray is minimal.
However, the more radiation the patient receives over the course of life
increases the risk of cell changes in the body or having cancerous tumors. The
radiation from this study is not expected to greatly increase these risks, but
the exact increase of such risks is unknown.

Fasting Blood Sample
The patient will be asked to fast for 8-10 hours prior to some study visits
which may cause dizziness, low blood sugar and in rare occasions, fainting.

Injection site reactions with abatacept The patient may experience pain,
redness, swelling, itching or bruising at the site of the study drug injection.



SLE risks:

Blood Sample
Blood samples will be collected during this study. A needle is inserted into a
vein in the patient's arm and a small blood sample is withdrawn. Although one
needle insertion for blood draw is usually sufficient, a second one may be
necessary if the first is not successful. Collecting blood samples may cause
fainting and some pain and/or bruising at the site on the patient's arm where
the blood was taken. In rare occasions, infection may occur.

ECG
ECG will be performed, which is a process of recording the electrical activity
of the heart over a short period of time using sticky pads placed on the skin
to measure the rate and rhythm of the patient's heartbeats. The sticky pads may
cause mild skin irritation.

X-ray
The patient may receive an X-ray as part of the study. An X-ray is a form of
radiation. The radiation the patient receives from the X-ray is minimal.
However, the more radiation the patient receives over the course of life
increases the risk of cell changes in the body or having cancerous tumors. The
radiation from this study is not expected to greatly increase these risks, but
the exact increase of such risks is unknown.

Fasting Blood Sample
The patient will be asked to fast for 8-10 hours prior to some study visits
which may cause dizziness, low blood sugar and in rare occasions, fainting.

General skin care measures are recommended that are standard for participants
with SLE, unless otherwise informed by the patient's doctor, e.g. to treat a
side effect. These general skin care measures include: use of broad spectrum
sunscreen (minimum sun protection factor 15 and with inorganic ingredients
(zinc oxide, titanium dioxide), avoiding sun exposure, wearing sun-protective
clothing, avoidance of alcohol-based emollients, avoidance of over-the-counter
anti-acne medications and alcohol-based skin care products, and avoidance of
perfumed soaps and detergents, and similar measures.

There may be risks or side effects related to the study drug or other study
procedures that are unknown at this time. Let the study doctor know if the
patient experiences any side effects, even those which are not mentioned in
this Information sheet. The study doctor will inform the patient (or legally
authorized representative) if new information on the study medication becomes
available that may affect the patient's decision to continue to take part in
the study.