A Study to Assess the Efficacy of RO5459072 in Participants With Primary Sjogren's Syndrome

Percentage of participants with a clinically relevant decrease in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Score is defined as participants with absolute decrease of ≥ 3-points in ESSDAI score. ESSDAI is physician-assessed disease activity index developed by EULAR consortium consisting of 44 items in 12 organ-specific 'domains' (constitutional,lymphadenopathy, articular,muscular,cutaneous,glandular,pulmonary,renal,peripheral nervous system,central nervous system,hematological,biological). Each domain is assessed for activity level (i.e., no, low, moderate, high) and assigned a numerical score based on pre-determined weighting of each individual domain. Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 (best) to 123 (worst activity). A score ≥ 5 is considered moderate or severe disease activity and a clinically relevant change in ESSDAI score is defined as absolute decrease of ≥ 3-points.

Time frame: 12 weeks

Population: Modified intent-to-treat (mITT) population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Average observed plasma concentration (mass/volume)

Time frame: Week 2, Week 6, and Week 12

Population: The safety population included all participants, who received at least one dose of the study medication. Participants were grouped according to the treatment actually received.

Anti-Sjögren's-syndrome-related antigen A is a type of antibody found in the auto-antibody titers.

Time frame: Baseline, Week 6, and Week 12

Population: The safety population included all participants, who received at least one dose of the study medication. Participants were grouped according to the treatment actually received.

Anti-Sjögren's-syndrome-related antigen B is a type of antibody found in the auto-antibody titers.

Time frame: Baseline, Week 6, and Week 12

Population: The safety population included all participants, who received at least one dose of the study medication. Participants were grouped according to the treatment actually received.

Change from baseline in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Score is defined as the change in score between baseline (Week -1) and Week 12. The ESSDAI is a physician-assessed disease activity index for primary Sjögren's syndrome developed by the EULAR consortium. It consists of 44 items in 12 organ-specific 'domains' contributing to disease activity (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, biological). Each domain is assessed for activity level (i.e., no, low, moderate, high) and assigned a numerical score based on pre-determined weighting of each individual domain. An overall score is then calculated as the sum of all individual weighted domain scores. Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 (best) to 123 (worst activity).

Time frame: Baseline (Week -1), Week 12

Population: mITT population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Change from baseline in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) dryness component score is defined as the change in score between baseline (Week -1) and Week 12. The Dryness Component score ranged from 0-10 (0 =no symptom at all and 10 = worst symptom imaginable).

Time frame: Baseline (Week -1), Week 12

Population: mITT population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Change from baseline in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) fatigue component score is defined as the change in score between baseline (Week -1) and Week 12. The ESSPRI score consists of three questions covering the cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable).

Time frame: Baseline (Week -1), Week 12

Population: mITT population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Change from baseline in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) Score is defined as the change in score between baseline (Week -1) and Week 12. The ESSPRI is a patient-reported, subjective symptom index for primary Sjögren's syndrome developed by the EULAR consortium. It consists of three questions covering the cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and an overall score is calculated as the mean of the three individual domains where all domains carry the same weight.

Time frame: Baseline (Week -1), Week 12

Population: mITT population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Change from baseline in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) pain component score is defined as the change in score between baseline (Week -1) and Week 12. The ESSPRI score consists of three questions covering the cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (Each domain scored on scale of 0-10 (0 = no symptom at all and 10 = worst symptom imaginable).

Time frame: Baseline (Week -1), Week 12

Population: mITT population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Change from baseline in mechanically stimulated salivary flow rate is defined as the change in flow (mL/min) between baseline (Week -1) and Week 2, Week 6 and Week 12. Using a mechanical stimulation method of a piece of neutral wax, paraffin, silicone, unflavored chewing gum, or similar chewable, unflavored, nonabsorbent material, patients were instructed to chew for a period of 5 minutes. The stimulated salivary flow rate was calculated assuming a specific gravity of 1 (i.e., 1 mL saliva = 1 g) and expressed in mL per minute.

Time frame: Baseline, Week 2, Week 6, and Week 12

Population: mITT population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Rheumatoid factor is a type of auto-antibody found in the auto-antibody titers.

Time frame: Baseline, Week 6, and Week 12

Population: The safety population included all participants, who received at least one dose of the study medication. Participants were grouped according to the treatment actually received.

Change from baseline in Short Form-36 Health Survey (SF-36) Physical Score is defined as the change in score between baseline (Week -1) and Week 12. The SF-36 was used to assess health-related quality of life at baseline and at on-treatment visits. The SF-36 consisted of 36 questions covering 8 domains (general health, physical functioning, role-functioning physical, bodily pain, social functioning, role-functioning emotional, mental health, and vitality), with each domain scoring on a scale 0-100. (a score of 0 = maximum disability and a score of 100 = no disability)

Time frame: Baseline (Week -1), Week 12

Population: mITT population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Change from baseline in Short Form-36 Health Survey (SF-36) Mental score is defined as the change in score between baseline (Week -1) and Week 12. The SF-36 was used to assess health-related quality of life at baseline and at on-treatment visits. The SF-36 consisted of 36 questions covering 8 domains (general health, physical functioning, role-functioning physical, bodily pain, social functioning, role-functioning emotional, mental health, and vitality), with each domain scoring on a scale 0-100 (a score of 0 = maximum disability and a score of 100 = no disability). Reported here is the mental health domain score.

Time frame: Baseline (Week -1), Week 12

Population: mITT population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Un-stimulated tear production rate was measured from both eyes (without the use of analgesics/ anesthetic drops) at baseline and at on-treatment visits using the Schirmer method. A thin strip of filter paper (Schirmer strip, e.g., 35 x 5 mm) was placed at the junction of the lateral and middle thirds of the lower eyelid of each eye. The maximum length of wetting along the strip at the end of the test period was measured.

Time frame: Baseline, Week 2, Week 6, and Week 12

Population: mITT population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Total IgG is a type of auto-antibody found in the auto-antibody titers.

Time frame: Baseline, Week 6, and Week 12

Population: The safety population included all participants, who received at least one dose of the study medication. Participants were grouped according to the treatment actually received.

Total IgM is a type of auto-antibody found in the auto-antibody titers.

Time frame: Baseline, Week 6, and Week 12

Population: The safety population included all participants, who received at least one dose of the study medication. Participants were grouped according to the treatment actually received.

Maximum observed plasma concentration (mass/volume)

Time frame: Week 2, Week 6, and Week 12

Population: The safety population included all participants, who received at least one dose of the study medication. Participants were grouped according to the treatment actually received.

Minimum observed plasma concentration (mass/volume)

Time frame: Week 2, Week 6, and Week 12

Population: The safety population included all participants, who received at least one dose of the study medication. Participants were grouped according to the treatment actually received.

The efficacy of RO5459072 in patients with primary Sjogren's Syndrome Disease is evaluated in terms of the percentage of participants with a clinically relevant decrease in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) Score, where a clinically relevant decrease in ESSPRI score is defined as a decrease of ≥ 1 point. The ESSPRI is a patient-reported, subjective symptom index for primary Sjögren's syndrome developed by the EULAR consortium. It consists of 3 questions covering cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and overall score is calculated as the mean of 3 individual domains where all domains carry same weight.

Time frame: 12 weeks

Population: mITT population was defined as all randomized participants, who received any study medication and had evaluable measument of the parameter of interest at baseline and at least one post-baseline visit.

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Time frame: Baseline up to Week 14

Population: The safety population included all participants, who received at least one dose of the study medication. Participants were grouped according to the treatment actually received.