Trial Outcomes & Findings for A Study to Assess the Efficacy of RO5459072 in Participants With Primary Sjogren's Syndrome (NCT NCT02701985)

NCT ID: NCT02701985

Last Updated: 2018-08-01

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 75 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2018-08-01

Participant Flow

A total of 75 patients were randomized in a 1:1 ratio to RO5459072 or placebo (38 patients in the RO5459072 treatment group and 37 patients in the placebo group).

Participant milestones

Measure	Placebo Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Overall Study STARTED	37	38
Overall Study COMPLETED	34	32
Overall Study NOT COMPLETED	3	6

Reasons for withdrawal

Measure	Placebo Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Overall Study Withdrawal by Subject	1	1
Overall Study Lost to Follow-up	1	0
Overall Study Death	1	0
Overall Study Adverse Event	0	5

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo n=37 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 Participants RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.	Total n=75 Participants Total of all reporting groups
Age, Continuous	52.3 years STANDARD_DEVIATION 11.8 • n=5 Participants	52.1 years STANDARD_DEVIATION 13.2 • n=7 Participants	52.2 years STANDARD_DEVIATION 12.5 • n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	32 Participants n=7 Participants	68 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	35 Participants n=5 Participants	38 Participants n=7 Participants	73 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	33 Participants n=5 Participants	35 Participants n=7 Participants	68 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo n=37 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 Participants RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Percentage of Participants With a Clinically Relevant Decrease in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Score	37.8 Percentage of Participants Interval 20.86 to 54.86	42.1 Percentage of Participants Interval 25.09 to 59.12

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo n=37 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 Participants RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Percentage of Participants With a Clinically Relevant Decrease in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) Score	56.8 Percentage of Participants Interval 39.44 to 74.07	57.9 Percentage of Participants Interval 40.88 to 74.91

SECONDARY outcome

Timeframe: 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 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).

Outcome measures

Measure	Placebo n=37 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 Participants RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Change From Baseline in ESSDAI Score at Week 12 Baseline in ESSDAI Score	11.27 scores on a scale Standard Deviation 5.71	11.79 scores on a scale Standard Deviation 4.69
Change From Baseline in ESSDAI Score at Week 12 Change From Baseline in ESSDAI Score at Week 12	-3.06 scores on a scale Standard Deviation 3.96	-3.25 scores on a scale Standard Deviation 4.09

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=37 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 Participants RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Change From Baseline in ESSPRI Score at Week 12 Baseline in ESSPRI Score	7.34 Score on a scale Standard Deviation 1.19	6.98 Score on a scale Standard Deviation 0.98
Change From Baseline in ESSPRI Score at Week 12 Change From Baseline in ESSPRI Score at Week 12	-1.35 Score on a scale Standard Deviation 1.67	-1.51 Score on a scale Standard Deviation 1.79

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=37 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 Participants RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Change From Baseline in Short Form 36 Health Survey (SF-36) Mental Score at Week 12 Baseline	42.09 Score on a scale Standard Deviation 11.18	40.52 Score on a scale Standard Deviation 9.27
Change From Baseline in Short Form 36 Health Survey (SF-36) Mental Score at Week 12 Change from Baseline at Week 12	4.52 Score on a scale Standard Deviation 7.15	3.02 Score on a scale Standard Deviation 9.04

SECONDARY outcome

Timeframe: 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) 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)

Outcome measures

Measure	Placebo n=37 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 Participants RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Change From Baseline in SF-36 Physical Score at Week 12 Baseline in SF-36 Physical Score	40.86 Score on a scale Standard Deviation 6.82	40.71 Score on a scale Standard Deviation 6.94
Change From Baseline in SF-36 Physical Score at Week 12 Change From Baseline at Week 12	2.46 Score on a scale Standard Deviation 6.09	3.01 Score on a scale Standard Deviation 5.10

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Placebo n=37 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 Participants RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Change From Baseline in ESSPRI Dryness Component Score at Week 12 Baseline	7.54 Score on a scale Standard Deviation 1.57	7.45 Score on a scale Standard Deviation 1.25
Change From Baseline in ESSPRI Dryness Component Score at Week 12 Change From Baseline at Week 12	-1.15 Score on a scale Standard Deviation 1.56	-1.77 Score on a scale Standard Deviation 2.29

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Placebo n=37 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 Participants RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Change From Baseline in ESSPRI Fatigue Component Score at Week 12 Baseline	7.22 Score on a scale Standard Deviation 1.81	7.24 Score on a scale Standard Deviation 1.84
Change From Baseline in ESSPRI Fatigue Component Score at Week 12 Change From Baseline at Week 12	-1.29 Score on a scale Standard Deviation 2.24	-1.94 Score on a scale Standard Deviation 2.16

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Placebo n=37 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 Participants RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Change From Baseline in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) Pain Component Score at Week 12 Baseline	7.27 Score on a scale Standard Deviation 1.71	6.26 Score on a scale Standard Deviation 2.05
Change From Baseline in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) Pain Component Score at Week 12 Change From Baseline at Week 12	-1.62 Score on a scale Standard Deviation 2.70	-0.97 Score on a scale Standard Deviation 2.56

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo n=37 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 Participants RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Change From Baseline in Tear Flow Rate at Weeks 2, 6, and 12 Baseline in Tear Flow Rate	7.53 mm/5 min Standard Deviation 9.66	7.84 mm/5 min Standard Deviation 10.15
Change From Baseline in Tear Flow Rate at Weeks 2, 6, and 12 Change from Baseline at Week 2	-0.54 mm/5 min Standard Deviation 5.02	-0.81 mm/5 min Standard Deviation 5.06
Change From Baseline in Tear Flow Rate at Weeks 2, 6, and 12 Change from Baseline at Week 6	-1.39 mm/5 min Standard Deviation 6.32	-0.95 mm/5 min Standard Deviation 7.95
Change From Baseline in Tear Flow Rate at Weeks 2, 6, and 12 Change from Baseline at Week 12	-2.38 mm/5 min Standard Deviation 6.47	-1.65 mm/5 min Standard Deviation 7.71

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo n=37 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 Participants RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Change From Baseline in Mechanically Stimulated Salivary Flow Rate at Weeks 2, 6, and 12 Baseline	0.45 mL/min Standard Deviation 0.29	0.55 mL/min Standard Deviation 0.58
Change From Baseline in Mechanically Stimulated Salivary Flow Rate at Weeks 2, 6, and 12 Change from Baseline at Week 2	0.10 mL/min Standard Deviation 0.33	-0.01 mL/min Standard Deviation 0.33
Change From Baseline in Mechanically Stimulated Salivary Flow Rate at Weeks 2, 6, and 12 Change from Baseline at Week 6	0.10 mL/min Standard Deviation 0.31	0.11 mL/min Standard Deviation 0.47
Change From Baseline in Mechanically Stimulated Salivary Flow Rate at Weeks 2, 6, and 12 Change from Baseline at Week 12	0.12 mL/min Standard Deviation 0.30	0.24 mL/min Standard Deviation 0.75

SECONDARY outcome

Timeframe: 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 A is a type of antibody found in the auto-antibody titers.

Outcome measures

Measure	Placebo n=37 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 Participants RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Change From Baseline in Anti-Sjögren's-Syndrome-Related Antigen A at Weeks 6, and 12 Baseline	214.52 U/mL Standard Deviation 58.06	217.78 U/mL Standard Deviation 53.96
Change From Baseline in Anti-Sjögren's-Syndrome-Related Antigen A at Weeks 6, and 12 Change from Baseline at Week 6	-4.82 U/mL Standard Deviation 16.05	-1.47 U/mL Standard Deviation 13.90
Change From Baseline in Anti-Sjögren's-Syndrome-Related Antigen A at Weeks 6, and 12 Change from Baseline at Week 12	-2.57 U/mL Standard Deviation 18.97	-5.20 U/mL Standard Deviation 11.65

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=37 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 Participants RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Change From Baseline in Anti-Sjögren's-Syndrome-Related Antigen B at Weeks 6, and 12 Baseline	101.66 U/mL Standard Deviation 130.48	76.94 U/mL Standard Deviation 120.76
Change From Baseline in Anti-Sjögren's-Syndrome-Related Antigen B at Weeks 6, and 12 Change from Baseline at Week 6	1.94 U/mL Standard Deviation 15.20	-2.55 U/mL Standard Deviation 13.09
Change From Baseline in Anti-Sjögren's-Syndrome-Related Antigen B at Weeks 6, and 12 Change from Baseline at Week 12	1.35 U/mL Standard Deviation 13.52	-4.47 U/mL Standard Deviation 12.32

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Placebo n=37 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 Participants RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Change From Baseline in Rheumatoid Factor at Weeks 6, and 12 Baseline in Rheumatoid Factor	43.00 kU/L Standard Deviation 48.51	117.84 kU/L Standard Deviation 336.82
Change From Baseline in Rheumatoid Factor at Weeks 6, and 12 Change from Baseline at Week 6	-1.50 kU/L Standard Deviation 10.74	-28.03 kU/L Standard Deviation 70.04
Change From Baseline in Rheumatoid Factor at Weeks 6, and 12 Change from Baseline at Week 12	-0.68 kU/L Standard Deviation 9.97	-57.77 kU/L Standard Deviation 173.75

SECONDARY outcome

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

Outcome measures

Measure	Placebo n=37 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 Participants RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Change From Baseline in Total Immunoglobulin G (IgG) at Weeks 6, and 12 Baseline in Total IgG	15.74 g/L Standard Deviation 6.77	13.59 g/L Standard Deviation 4.92
Change From Baseline in Total Immunoglobulin G (IgG) at Weeks 6, and 12 Change from Baseline at Week 6	0.11 g/L Standard Deviation 1.51	-0.30 g/L Standard Deviation 1.21
Change From Baseline in Total Immunoglobulin G (IgG) at Weeks 6, and 12 Change from Baseline at Week 12	0.48 g/L Standard Deviation 1.78	-0.50 g/L Standard Deviation 1.13

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=37 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 Participants RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Change From Baseline in Total Immunoglobulin M (IgM) at Weeks 6, and 12 Baseline in Total IgM	1.24 g/L Standard Deviation 0.82	1.26 g/L Standard Deviation 0.75
Change From Baseline in Total Immunoglobulin M (IgM) at Weeks 6, and 12 Change from Baseline at Week 6	0.03 g/L Standard Deviation 0.20	-0.10 g/L Standard Deviation 0.17
Change From Baseline in Total Immunoglobulin M (IgM) at Weeks 6, and 12 Change from Baseline at Week 12	0.06 g/L Standard Deviation 0.25	-0.17 g/L Standard Deviation 0.20

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Placebo n=38 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Minimum Concentration (Cmin) of RO5459072	1340 ng/mL Interval 2.68 to 2900.0	—

SECONDARY outcome

Timeframe: 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.

Maximum observed plasma concentration (mass/volume)

Outcome measures

Measure	Placebo n=38 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Maximum Concentration (Cmax) of RO5459072	2350 ng/mL Interval 1140.0 to 3610.0	—

SECONDARY outcome

Timeframe: 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.

Average observed plasma concentration (mass/volume)

Outcome measures

Measure	Placebo n=38 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Average Concentration (Caverage) of RO5459072	1740 ng/mL Interval 816.0 to 3187.0	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo n=37 Participants Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 Participants RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Percentage of Participants With Adverse Events	78.4 Percentage of participants	76.3 Percentage of participants

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 19 other events

Deaths: 1 deaths

RO5459072

Serious events: 1 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=37 participants at risk Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 participants at risk RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Blood and lymphatic system disorders Iron Deficiency Anaemia	0.00% 0/37 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	2.6% 1/38 • Number of events 1 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
Cardiac disorders Cardiac Arrest	2.7% 1/37 • Number of events 1 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	0.00% 0/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
Metabolism and nutrition disorders Metabolic Acidosis	2.7% 1/37 • Number of events 1 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	0.00% 0/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
Nervous system disorders Headache	2.7% 1/37 • Number of events 1 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	0.00% 0/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.

Other adverse events

Measure	Placebo n=37 participants at risk Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 n=38 participants at risk RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Gastrointestinal disorders Abdominal Pain	2.7% 1/37 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	7.9% 3/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
Gastrointestinal disorders Diarrhoea	5.4% 2/37 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	5.3% 2/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
Gastrointestinal disorders Dyspepsia	5.4% 2/37 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	0.00% 0/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
Gastrointestinal disorders Nausea	0.00% 0/37 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	13.2% 5/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
General disorders Fatigue	2.7% 1/37 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	5.3% 2/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
General disorders Pyrexia	5.4% 2/37 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	0.00% 0/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
Infections and infestations Bronchitis	5.4% 2/37 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	2.6% 1/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
Infections and infestations Influenza	2.7% 1/37 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	5.3% 2/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
Infections and infestations Sinusitis	8.1% 3/37 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	2.6% 1/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
Infections and infestations Upper Respiratory Tract Infection	5.4% 2/37 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	13.2% 5/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
Infections and infestations Viral Upper Respiratory Tract Infection	5.4% 2/37 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	15.8% 6/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
Investigations Blood Thyroid Stimulating Hormone Decreased	0.00% 0/37 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	5.3% 2/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
Musculoskeletal and connective tissue disorders Arthralgia	2.7% 1/37 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	7.9% 3/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
Nervous system disorders Headache	10.8% 4/37 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	13.2% 5/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/37 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	5.3% 2/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
Skin and subcutaneous tissue disorders Pruritus	5.4% 2/37 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	5.3% 2/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
Skin and subcutaneous tissue disorders Rash	2.7% 1/37 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	13.2% 5/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/37 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.	13.2% 5/38 • The total duration of the study for each patient was (up to) 19 weeks. The safety population is defined as all patients who received at least one dose of the study medication.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER