Key
Inclusion Criteria:
Inclusion Criteria for GCA:
1. Male or non-pregnant, non-lactating female participants at least 50 years of age. 2. Diagnosis of GCA based on meeting all of the following criteria:
- - Unequivocal cranial symptoms of GCA (e.g., new-onset localized headache, scalp or
temporal artery tenderness, permanent or temporary ischemia-related vision loss,
or otherwise unexplained mouth or jaw pain upon mastication), and/or unequivocal
symptoms of PMR (defined as shoulder and/or hip girdle pain associated with
inflammatory morning stiffness) and/or symptoms of limb ischemia (claudication)
- Temporal artery biopsy (TAB) revealing features of GCA and/or cross-sectional
imaging study such as ultrasound (e.g., cranial or axillary), MRI/MRA, CTA, or
PET-CT with evidence of vasculitis.
3. Active GCA disease within 6 months prior to Baseline as defined by meeting both of the
following:
- - Presence of signs or symptoms attributed to active GCA and not related to prior
damage (e.g., vision loss that occurred without new findings)
- Elevated ESR >= 30 mm/hr or CRP >= 10 mg/L attributed to active GCA or active GCA
on TAB or on imaging study.
Inclusion Criteria for PMR:
1. Male or non-pregnant, non-lactating female participants at least 50 years of age. 2. Diagnosis of PMR according to the provisional ACR/EULAR classification criteria:
Participants >= 50 years of age with a history of bilateral shoulder pain accompanied
by elevated CRP concentration (>= 10 mg/L) and/or elevated ESR (>= 30 mm/hr) who
scored at least 4 points from the following optional classification criteria:
- - Morning stiffness >45 min (2 points)
- Hip pain or restricted range of motion (1 point)
- Absence of rheumatoid factor and/or anti-citrullinated protein antibodies (2
points)
- Absence of other joint involvement (1 point)
3.
Active PMR disease within 6 months prior to Baseline as defined by signs and symptoms
attributable to PMR meeting the following:
- - Bilateral shoulder girdle and/or bilateral hip girdle pain associated with
inflammatory stiffness with or without additional symptoms indicative of a PMR
relapse (such as constitutional symptoms) that are in the opinion of the
Investigator not due to other diseases that may mimic PMR such as osteoarthritis
in shoulders or hips, polyarticular calcium pyrophosphate deposition disease,
rotator cuff disease, adhesive capsulitis (frozen shoulder) or fibromyalgia.
Key
Exclusion Criteria:
Exclusion Criteria for GCA:
1. Pregnant or nursing (lactating) women where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive human chorionic gonadotropin (hCG) laboratory test. 2. History of hypersensitivity or contraindication to any of the study treatments or its
excipients or to drugs of similar chemical classes. 3. Use of other investigational drugs within 5 half-lives of enrollment or within 30 days
(e.g., small molecules) or until the expected pharmacodynamic effect has returned to
BSL (e.g., biologics), whichever is longer; or longer if required by local regulations. 4. History of clinically significant liver disease or liver injury as indicated by
clinically significantly abnormal liver function tests (LFTs), such as SGOT (AST),
SGPT (ALT) and serum bilirubin. The Investigator should be guided by the following
criteria:
- - AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase) may not
exceed 3 x the upper limit of normal (ULN)
- Total bilirubin concentration may not exceed 1.5 x ULN Any one of these
parameters, if elevated above ULN, should be re-checked once more as soon as
possible, and in all cases, at least prior to enrollment, to rule-out laboratory
error.
5. Active infections or history of ongoing, chronic or recurrent infectious disease
including but not limited to below:
- - Active infections during the last 2 weeks prior to BSL.
- - Known infection with human immunodeficiency virus (HIV), hepatitis B (HBV) or
hepatitis C (HCV) at screening or BSL, except for HCV successfully treated and
cured, according to local/global guidelines.
- - Evidence of tuberculosis (TB) infection as defined by a positive QuantiFERON
TB-Gold Plus test.
Participants with a positive test may participate in the study
if further work-up (according to local practice/guidelines) establishes
conclusively that the participant has no evidence of active TB. If the test
result is indeterminate, the Investigator may repeat the test once or may proceed
directly to perform the work-up for TB as per local procedures. If presence of
latent TB is established, then treatment must be initiated prior to BSL (both
treatment and timing prior to BSL according to local country guidelines)
6. Active inflammatory bowel disease or active uveitis. 7. Active ongoing diseases which in the opinion of the Investigator immuno-compromises
the participant and/or places the participant at unacceptable risk for treatment with
immunomodulatory therapy. 8. Current severe progressive or uncontrolled disease, which in the judgment of the
Investigator renders the participant unsuitable for the trial, including but not
limited to below:
- - Major ischemic event (e.g., myocardial infarction, stroke, etc.) or transient
ischemic attack (TIA) within 12 weeks of screening.
- - Significant medical conditions or diseases, including but not limited to the
following: uncontrolled hypertension, congestive heart failure (New York Heart
Association (NYHA) status of class III or IV) and uncontrolled diabetes mellitus.
- - Any other current severe progressive or uncontrolled diseases per the
Investigator's discretion.
9. Confirmed diagnosis of any primary form of systemic vasculitis, other than GCA. Exclusion Criteria for PMR:
1. Pregnant or nursing (lactating) women where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive human chorionic gonadotropin (hCG) laboratory test. 2. History of hypersensitivity or contraindication to any of the study treatments or its
excipients or to drugs of similar chemical classes. 3. Use of other investigational drugs within 5 half-lives of enrollment or within 30 days
(e.g., small molecules) or until the expected pharmacodynamic effect has returned to
BSL (e.g., biologics), whichever is longer; or longer if required by local regulations. 4. History of clinically significant liver disease or liver injury as indicated by
clinically significantly abnormal liver function tests (LFTs), such as SGOT (AST),
SGPT (ALT) and serum bilirubin. The Investigator should be guided by the following
criteria:
- - AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase) may not
exceed 3 x the upper limit of normal (ULN)
- Total bilirubin concentration may not exceed 1.5 x ULN Any one of these
parameters, if elevated above ULN, should be re-checked once more as soon as
possible, and in all cases, at least prior to enrollment, to rule-out laboratory
error.
5. Active infections or history of ongoing, chronic or recurrent infectious disease
including but not limited to below:
- - Active infections during the last 2 weeks prior to BSL.
- - Known infection with human immunodeficiency virus (HIV), hepatitis B (HBV) or
hepatitis C (HCV) at screening or BSL, except for HCV successfully treated and
cured, according to local/global guidelines.
- - Evidence of TB infection as defined by a positive QuantiFERON TB-Gold Plus test.
Participants with a positive test may participate in the study if further work-up
(according to local practice/guidelines) establishes conclusively that the
participant has no evidence of active TB. If the test result is indeterminate,
the Investigator may repeat the test once or may proceed directly to perform the
work-up for TB as per local procedures. If presence of latent TB is established,
then treatment must be initiated prior to BSL (both treatment and timing prior to
BSL according to local country guidelines)
6. Active inflammatory bowel disease or active uveitis. 7. Active ongoing diseases which in the opinion of the Investigator immuno-compromises
the participant and/or places the participant at unacceptable risk for treatment with
immunomodulatory therapy. 8. Current severe progressive or uncontrolled disease, which in the judgment of the
Investigator renders the participant unsuitable for the trial, including but not
limited to below:
- - Major ischemic event (e.g., myocardial infarction, stroke, etc.) or transient
ischemic attack (TIA) within 12 weeks of screening.
- - Significant medical conditions or diseases, including but not limited to the
following: uncontrolled hypertension, congestive heart failure (New York Heart
Association (NYHA) status of class III or IV) and uncontrolled diabetes mellitus.
- - Any other current severe progressive or uncontrolled diseases per the
Investigator's discretion.
9. Evidence of GCA as indicated by typical (cranial) symptoms (e.g., persistent or
recurrent localized headache, temporal artery or scalp tenderness, jaw claudication,
blurry or loss of vision, symptoms of stroke), extremity claudication, imaging and/or
temporal artery biopsy result. • Note: Imaging and/or temporal artery biopsy are not standard of care for PMR
management and diagnosis and are therefore not mandated as part of the screening;
Patients with PMR symptoms only who have a temporal artery biopsy in line with GCA
and/or radiologic signs of vasculitis may be eligible for the GCA cohort. 10. Concurrent rheumatoid arthritis or other inflammatory arthritis or other connective
tissue diseases, such as but not limited to systemic lupus erythematosus, systemic
sclerosis, vasculitis, myositis, mixed connective tissue disease, and ankylosing
spondylitis. 11. Concurrent diagnosis or history of neuropathic muscular diseases including
fibromyalgia. 12. Inadequately treated hypothyroidism (e.g., persistence of symptoms, lack of
normalization of serum TSH despite regular hormonal replacement treatment)
Additional protocol-defined inclusion / exclusion criteria may apply.
