Rheumatoid Arthritis
Conditions
Brief summary
A study to evaluate the long-term safety and efficacy of GDC-0853 in participants with moderate to severe active Rheumatoid Arthritis (RA) who have completed 12 weeks of study treatment in Study GA29350. Eligible participants from Study GA29350 who elect to participate will receive treatment with GDC-0853 twice daily (BID) in an open-label fashion for 52 weeks, followed by a safety follow-up period of 8 weeks.
Interventions
DRUGGDC-0853
GDC-0853 was administered orally at a dose of 200mg, as per the dosing schedules described above.
Sponsors
Genentech, Inc.
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 76 Years
Healthy volunteers
No
Inclusion criteria
* Completion of treatment as specified in Study GA29350, including completion of the Day 84 study visit assessments * Acceptable safety and tolerability during Study GA29350 as determined by the investigator or Medical Monitor * Have not received any prohibited medications in Study GA29350 * While taking methotrexate, must be willing to receive oral folic acid (at least 5 milligrams per week \[mg/week\]) * If receiving oral corticosteroids (less than or equal to \[\</=\] 10 milligrams per day \[mg/day\] prednisone or equivalent) and/or non-steroidal anti-inflammatory drugs, doses have remained stable for the duration of Study GA29350
Exclusion criteria
* Met protocol defined treatment stopping criteria during Study GA29350 * Treatment with any investigational agent (i.e., other than study drug) or live/attenuated vaccine or any other prohibited medication during Study GA29350 or since the last administration of study drug in Study GA29350 * In the opinion of the investigator, any new (since initially enrolling in the Phase II Study GA29350), significant, uncontrolled comorbidity that would increase the risk to the participant in Study GA30067 * Pregnant or lactating, or intending to become pregnant during the study * Participants who experienced a de novo or reactivated serious viral infection such as hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) during the Phase II Study GA29350 * Any major episode of infection requiring hospitalization or treatment with intravenous antibiotics during the Phase II Study GA29350 * Participants who developed a malignancy during the Phase II Study GA29350 * 12-lead electrocardiogram (ECG) on Day 84 in Study GA29350 that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results * Current treatment with medications that are well known to prolong the QT interval
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs) | Day 1 up until 8 weeks after the last dose of study drug (up to 1 year, 2 months) | An Adverse Event (AE) was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. |
| Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Week 52 | Week 52 | ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Weeks 4, 8, 12, 24, 36 and 52 | ACR70 response is defined as a ≥ 70% improvement (reduction) compared with Baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\]. |
| Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 CRP) | Baseline, Weeks 4, 8, 12, 24, 36 and 52 | The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6. |
| Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 CRP) | Baseline, Weeks 4, 8, 12, 24, 36 and 52 | The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6. |
| Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 ESR) | Baseline, Weeks 4, 8, 12, 24, 36 and 52 | The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6. |
| Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 ESR) | Baseline, Weeks 4, 8, 12, 24, 36 and 52 | The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6. |
| Percentage of Participants With Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) | Weeks 4, 8, 12, 24, 36 and 52 | The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. |
| Percentage of Participants With Low Disease Activity (LDA) Based on DAS28 | Weeks 4, 8, 12, 24, 36 and 52 | The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. LDAS is defined as DAS28 ≤ 3.2 |
| Percentage of Participants With ACR/EULAR Remission | Weeks 4, 8, 12, 24, 36 and 52 | Assessed according to the Boolean based definition (tender joint count =\<1, swollen joint count =\<1, C-reactive Protein (CRP) =\<1, and patient global assessment =\<1) |
| Change From Baseline in Simplified Disease Activity Index (SDAI) | Weeks 4, 8, 12, 24, 36 and 52 | Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity |
| Change From Baseline in Clinical Disease Activity Index (CDAI) | Weeks 4, 8, 12, 24, 36 and 52 | CDAI was derived as the sum of the following: tender joint count (TJC), swollen joint count (SJC), participant global assessment (PGA) of disease activity, and physician assessment of disease activity. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA and physician assessment of disease activity were scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity. The total CDAI score range was 0-76, where higher scores indicate increased disease activity. Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest. Negative values indicate improvement/reduction in RA disease activity. |
| Change From Baseline in Tender/Painful Joint Count Based on 68 Joints | Weeks 4, 8, 12, 24, 36 and 52 | Tender Joint Count: a total of 68 joints will be assessed for tenderness. Each joint is assessed for the presence/absence of tenderness. 68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68. A negative change from Baseline indicated improvement. |
| Percentage of Participants Achieving ACR50 Response up to Week 12 | Weeks 4, 8 and 12 | ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\]. |
| Change From Baseline in Patient's Assessment of Arthritis Pain, Using Visual Analog Scale (VAS) Score | Weeks 4, 8, 12, 24, 36 and 52 | Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain |
| Change From Baseline in Patient's Global Assessment of Arthritis, Using VAS Score | Weeks 4, 8, 12, 24, 36 and 52 | Participant-assessed arthritis pain was scored on a 100-mm VAS, where the distance from 0 mm represented the participant's self evaluation of arthritis pain (0 mm=none; 100 mm=very severe). Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest, where negative change indicated a decrease in participant-assessed arthritis pain. |
| Change From Baseline in Physician's Global Assessment of Arthritis, Using VAS Score | Weeks 4, 8, 12, 24, 36 and 52 | Physician's assessment of participant's disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the physician's assessment of the participant's disease activity (0 mm=very good; 100 mm=very poor). Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest, where negative change from baseline indicated an improvement in physician-assessed disease activity. |
| Change From Baseline in C-Reactive Protein (CRP) Levels | Weeks 4, 8, 12, 24, 36 and 52 | C-reactive protein is a biological marker of inflammation and is measured in milligrams per decilitre (mg/dL) |
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Weeks 4, 8, 12, 24, 36 and 52 | The Stanford Health Assessment Questionnaire disability index is a patient-reported outcome used to assess difficulty in performing activities of daily living. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. To respond to each question, a four-level response with higher scores showing larger functional limitations, was chosen. Scoring is as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. The composite HAQ-DI score is the mean of the eight domain scores and the score ranges from 0 (no functional impairment) to 3 (maximum functional impairment). A negative change from baseline indicates improvement. |
| Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components | Weeks 12, 24 and 52 | The 36-Item Short Form Health Survey (SF-36v2) is a questionnaire used to assess functional health and well-being and consists of eight domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. The SF-36v2 is summarized into Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. The PCS and MCS scores range from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score | Weeks 12, 24 and 52 | The FACIT-Fatigue Scale consists of 13 items designed to measure the degree of fatigue experienced by the patient in the previous 7 days. For each question, there are five possible responses: 0 (not at all), 1 (a little bit), 2 (somewhat), 3 (quite a bit), 4 (very much). A total fatigue score is calculated by summing all items, and possible total scores range from 0 (maximum fatigue) to 52 (no fatigue). A positive change from baseline indicates an improvement in the patient's fatigue (less fatigue). |
| Area Under the Concentration Time Curve (AUC) of GDC-0853 at Steady State (AUC,ss) | Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination | Population PK model estimated AUC of GDC-0853 at steady-state. AUC was measured in Nanograms (ng) per millilitre(mL)\*hour (hr). |
| Minimum Plasma Concentration of GDC-0853 at Steady State (Ctrough,ss) | Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination | Population PK model estimated minimal plasma concentration (Ctrough) of GDC-0853 at steady-state (ss). |
| Plasma Decay Half-Life of GDC-0853 at Steady State (t1/2,ss) | Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination | Population PK model estimated plasma decay half life of GDC-0853 at steady-state. |
| Apparent Oral Clearance of GDC-0853 at Steady State (CL/F,ss) | Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination | Population PK model estimated apparent oral clearance of GDC-0853 at steady-state. |
| Change From Baseline in Swollen Joint Count Based on 66 Joints | Weeks 4, 8, 12, 24, 36 and 52 | Swollen Joint Count: a total of 66 joints will be assessed for swelling. Each joint is assessed for the presence/absence of swelling. 66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. A negative change from Baseline indicated improvement. |
| Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response | Weeks 4, 8, 12, 24, 36 and 52 | ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\] |
Countries
Argentina, Brazil, Bulgaria, Colombia, Mexico, Poland, Russia, Serbia, Ukraine, United States
Participant flow
Recruitment details
The study was conducted at 138 centers in 19 countries.
Pre-assignment details
496 participants were enrolled into this OLE study and were included in the ITT and Safety populations.
Participants by arm
| Arm | Count |
|---|---|
| GDC-0853 (200mg BID) Cohort 1 Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | 410 |
| GDC-0853 (200mg BID) Cohort 2 Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. | 86 |
| Total | 496 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 21 | 3 |
| Overall Study | Death | 3 | 0 |
| Overall Study | Lack of Efficacy | 8 | 1 |
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Multiple Reasons | 2 | 1 |
| Overall Study | Physician Decision | 3 | 1 |
| Overall Study | Withdrawal by Subject | 19 | 8 |
Baseline characteristics
| Characteristic | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 | Total |
|---|---|---|---|
| Age, Continuous | 49.9 Years STANDARD_DEVIATION 11.7 | 53.5 Years STANDARD_DEVIATION 12.5 | 50.5 Years STANDARD_DEVIATION 11.9 |
| Race/Ethnicity, Customized American Indian or Alaska native | 27 Participants | 11 Participants | 38 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants | 2 Participants | 9 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 136 Participants | 30 Participants | 166 Participants |
| Race/Ethnicity, Customized Multiple | 7 Participants | 2 Participants | 9 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 267 Participants | 56 Participants | 323 Participants |
| Race/Ethnicity, Customized Not Stated | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown | 5 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 365 Participants | 71 Participants | 436 Participants |
| Sex: Female, Male Female | 334 Participants | 64 Participants | 398 Participants |
| Sex: Female, Male Male | 76 Participants | 22 Participants | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 410 | 0 / 86 |
| other Total, other adverse events | 22 / 410 | 4 / 86 |
| serious Total, serious adverse events | 26 / 410 | 4 / 86 |
Outcome results
Primary
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Week 52
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].
Time frame: Week 52
Population: The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Week 52 | 57.1 Percentage |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Week 52 | 50.0 Percentage |
Primary
Percentage of Participants With Adverse Events (AEs)
An Adverse Event (AE) was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events.
Time frame: Day 1 up until 8 weeks after the last dose of study drug (up to 1 year, 2 months)
Population: The Safety-Evaluable Population was defined as all participants who received any study drug and had at least one assessment of safety.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants With Adverse Events (AEs) | 60.2 Percentage |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants With Adverse Events (AEs) | 57.0 Percentage |
Secondary
Apparent Oral Clearance of GDC-0853 at Steady State (CL/F,ss)
Population PK model estimated apparent oral clearance of GDC-0853 at steady-state.
Time frame: Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination
Population: The PK-Evaluable population was defined as all participants that received any fenebrutinib/GDC-0853 and had sufficient data to enable estimation of key PK parameters. Participants who received incorrect therapy different from the intended therapy were summarized in the group according to the therapy actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Apparent Oral Clearance of GDC-0853 at Steady State (CL/F,ss) | 39.5 L/hr | Standard Deviation 12.6 |
| GDC-0853 (200mg BID) Cohort 2 | Apparent Oral Clearance of GDC-0853 at Steady State (CL/F,ss) | 35.3 L/hr | Standard Deviation 10.3 |
Secondary
Area Under the Concentration Time Curve (AUC) of GDC-0853 at Steady State (AUC,ss)
Population PK model estimated AUC of GDC-0853 at steady-state. AUC was measured in Nanograms (ng) per millilitre(mL)\*hour (hr).
Time frame: Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination
Population: The PK-Evaluable population was defined as all participants that received any fenebrutinib/GDC-0853 and had sufficient data to enable estimation of key PK parameters. Participants who received incorrect therapy different from the intended therapy were summarized in the group according to the therapy actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Area Under the Concentration Time Curve (AUC) of GDC-0853 at Steady State (AUC,ss) | 13400 Ng/mL*(hr) | Standard Deviation 6930 |
| GDC-0853 (200mg BID) Cohort 2 | Area Under the Concentration Time Curve (AUC) of GDC-0853 at Steady State (AUC,ss) | 15600 Ng/mL*(hr) | Standard Deviation 7850 |
Secondary
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components
The 36-Item Short Form Health Survey (SF-36v2) is a questionnaire used to assess functional health and well-being and consists of eight domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. The SF-36v2 is summarized into Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. The PCS and MCS scores range from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.
Time frame: Weeks 12, 24 and 52
Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were actually collected is indicated for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components | Week 24 (Physical Component Score change) | 12.31 Number on a Scale | Standard Deviation 9.12 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components | Week 24 (Mental Component Score change) | 6.63 Number on a Scale | Standard Deviation 13.23 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components | Week 12 (Physical Component Score change) | 11.35 Number on a Scale | Standard Deviation 9.13 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components | Week 52 (Physical Component Score change) | 13.89 Number on a Scale | Standard Deviation 9.32 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components | Week 52 (Mental Component Score change) | 7.00 Number on a Scale | Standard Deviation 13.81 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components | Week 12 (Mental Component Score change) | 6.52 Number on a Scale | Standard Deviation 12.98 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components | Week 52 (Mental Component Score change) | 6.77 Number on a Scale | Standard Deviation 11.6 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components | Week 24 (Physical Component Score change) | 8.28 Number on a Scale | Standard Deviation 8.53 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components | Week 52 (Physical Component Score change) | 10.42 Number on a Scale | Standard Deviation 8.94 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components | Week 12 (Physical Component Score change) | 8.22 Number on a Scale | Standard Deviation 8.73 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components | Week 24 (Mental Component Score change) | 6.08 Number on a Scale | Standard Deviation 11.76 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components | Week 12 (Mental Component Score change) | 4.74 Number on a Scale | Standard Deviation 11.53 |
Secondary
Change From Baseline in Clinical Disease Activity Index (CDAI)
CDAI was derived as the sum of the following: tender joint count (TJC), swollen joint count (SJC), participant global assessment (PGA) of disease activity, and physician assessment of disease activity. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA and physician assessment of disease activity were scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity. The total CDAI score range was 0-76, where higher scores indicate increased disease activity. Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest. Negative values indicate improvement/reduction in RA disease activity.
Time frame: Weeks 4, 8, 12, 24, 36 and 52
Population: The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. Number of participants for whom data were actually collected is indicated for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 4 | -23.41 Score on a Scale | Standard Deviation 13.11 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 8 | -25.14 Score on a Scale | Standard Deviation 13.06 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 12 | -26.82 Score on a Scale | Standard Deviation 12.31 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 24 | -28.52 Score on a Scale | Standard Deviation 12.52 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 36 | -29.40 Score on a Scale | Standard Deviation 12.99 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 52 | -30.61 Score on a Scale | Standard Deviation 12.43 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 36 | -26.66 Score on a Scale | Standard Deviation 12.98 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 4 | -19.81 Score on a Scale | Standard Deviation 13.15 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 24 | -25.09 Score on a Scale | Standard Deviation 13.18 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 8 | -22.48 Score on a Scale | Standard Deviation 12.59 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 52 | -27.43 Score on a Scale | Standard Deviation 13.43 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 12 | -23.82 Score on a Scale | Standard Deviation 12.37 |
Secondary
Change From Baseline in C-Reactive Protein (CRP) Levels
C-reactive protein is a biological marker of inflammation and is measured in milligrams per decilitre (mg/dL)
Time frame: Weeks 4, 8, 12, 24, 36 and 52
Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were actually collected is indicated for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in C-Reactive Protein (CRP) Levels | Week 4 | -0.95 (mg/dL) | Standard Deviation 2.18 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in C-Reactive Protein (CRP) Levels | Week 8 | -1.02 (mg/dL) | Standard Deviation 2.41 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in C-Reactive Protein (CRP) Levels | Week 12 | -1.03 (mg/dL) | Standard Deviation 2.21 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in C-Reactive Protein (CRP) Levels | Week 24 | -1.03 (mg/dL) | Standard Deviation 2.48 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in C-Reactive Protein (CRP) Levels | Week 36 | -1.11 (mg/dL) | Standard Deviation 2.44 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in C-Reactive Protein (CRP) Levels | Week 52 | -1.12 (mg/dL) | Standard Deviation 2.55 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in C-Reactive Protein (CRP) Levels | Week 36 | -1.56 (mg/dL) | Standard Deviation 3.04 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in C-Reactive Protein (CRP) Levels | Week 4 | -1.09 (mg/dL) | Standard Deviation 3.1 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in C-Reactive Protein (CRP) Levels | Week 24 | -1.46 (mg/dL) | Standard Deviation 2.99 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in C-Reactive Protein (CRP) Levels | Week 8 | -1.58 (mg/dL) | Standard Deviation 2.6 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in C-Reactive Protein (CRP) Levels | Week 52 | -1.81 (mg/dL) | Standard Deviation 2.75 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in C-Reactive Protein (CRP) Levels | Week 12 | -1.40 (mg/dL) | Standard Deviation 3.38 |
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score
The FACIT-Fatigue Scale consists of 13 items designed to measure the degree of fatigue experienced by the patient in the previous 7 days. For each question, there are five possible responses: 0 (not at all), 1 (a little bit), 2 (somewhat), 3 (quite a bit), 4 (very much). A total fatigue score is calculated by summing all items, and possible total scores range from 0 (maximum fatigue) to 52 (no fatigue). A positive change from baseline indicates an improvement in the patient's fatigue (less fatigue).
Time frame: Weeks 12, 24 and 52
Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were actually collected is indicated for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score | Week 12 | 11.44 Score on a Scale | Standard Deviation 10.36 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score | Week 24 | 11.74 Score on a Scale | Standard Deviation 10.75 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score | Week 52 | 12.87 Score on a Scale | Standard Deviation 10.58 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score | Week 12 | 9.28 Score on a Scale | Standard Deviation 8.51 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score | Week 24 | 10.41 Score on a Scale | Standard Deviation 8.51 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score | Week 52 | 10.87 Score on a Scale | Standard Deviation 9.25 |
Secondary
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
The Stanford Health Assessment Questionnaire disability index is a patient-reported outcome used to assess difficulty in performing activities of daily living. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. To respond to each question, a four-level response with higher scores showing larger functional limitations, was chosen. Scoring is as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. The composite HAQ-DI score is the mean of the eight domain scores and the score ranges from 0 (no functional impairment) to 3 (maximum functional impairment). A negative change from baseline indicates improvement.
Time frame: Weeks 4, 8, 12, 24, 36 and 52
Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were actually collected is indicated for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 12 | -0.80 Score on a Scale | Standard Deviation 0.67 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 4 | -0.70 Score on a Scale | Standard Deviation 0.64 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 8 | -0.77 Score on a Scale | Standard Deviation 0.65 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 24 | -0.83 Score on a Scale | Standard Deviation 0.66 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 36 | -0.89 Score on a Scale | Standard Deviation 0.63 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 52 | -0.98 Score on a Scale | Standard Deviation 0.64 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 12 | -0.60 Score on a Scale | Standard Deviation 0.59 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 52 | -0.69 Score on a Scale | Standard Deviation 0.62 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 36 | -0.62 Score on a Scale | Standard Deviation 0.66 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 4 | -0.55 Score on a Scale | Standard Deviation 0.56 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 24 | -0.63 Score on a Scale | Standard Deviation 0.58 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 8 | -0.59 Score on a Scale | Standard Deviation 0.62 |
Secondary
Change From Baseline in Patient's Assessment of Arthritis Pain, Using Visual Analog Scale (VAS) Score
Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain
Time frame: Weeks 4, 8, 12, 24, 36 and 52
Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were actually collected is indicated for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Patient's Assessment of Arthritis Pain, Using Visual Analog Scale (VAS) Score | Week 4 | -30.62 Score on a Scale | Standard Deviation 26.6 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Patient's Assessment of Arthritis Pain, Using Visual Analog Scale (VAS) Score | Week 8 | -32.57 Score on a Scale | Standard Deviation 26.77 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Patient's Assessment of Arthritis Pain, Using Visual Analog Scale (VAS) Score | Week 12 | -35.68 Score on a Scale | Standard Deviation 26.44 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Patient's Assessment of Arthritis Pain, Using Visual Analog Scale (VAS) Score | Week 24 | -37.19 Score on a Scale | Standard Deviation 26.85 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Patient's Assessment of Arthritis Pain, Using Visual Analog Scale (VAS) Score | Week 36 | -39.50 Score on a Scale | Standard Deviation 27.2 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Patient's Assessment of Arthritis Pain, Using Visual Analog Scale (VAS) Score | Week 52 | -42.40 Score on a Scale | Standard Deviation 26.22 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Patient's Assessment of Arthritis Pain, Using Visual Analog Scale (VAS) Score | Week 36 | -33.14 Score on a Scale | Standard Deviation 27.22 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Patient's Assessment of Arthritis Pain, Using Visual Analog Scale (VAS) Score | Week 4 | -26.34 Score on a Scale | Standard Deviation 25.98 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Patient's Assessment of Arthritis Pain, Using Visual Analog Scale (VAS) Score | Week 24 | -30.30 Score on a Scale | Standard Deviation 26.42 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Patient's Assessment of Arthritis Pain, Using Visual Analog Scale (VAS) Score | Week 8 | -27.21 Score on a Scale | Standard Deviation 23.36 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Patient's Assessment of Arthritis Pain, Using Visual Analog Scale (VAS) Score | Week 52 | -38.21 Score on a Scale | Standard Deviation 26.37 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Patient's Assessment of Arthritis Pain, Using Visual Analog Scale (VAS) Score | Week 12 | -29.49 Score on a Scale | Standard Deviation 26.7 |
Secondary
Change From Baseline in Patient's Global Assessment of Arthritis, Using VAS Score
Participant-assessed arthritis pain was scored on a 100-mm VAS, where the distance from 0 mm represented the participant's self evaluation of arthritis pain (0 mm=none; 100 mm=very severe). Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest, where negative change indicated a decrease in participant-assessed arthritis pain.
Time frame: Weeks 4, 8, 12, 24, 36 and 52
Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were actually collected is indicated for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Patient's Global Assessment of Arthritis, Using VAS Score | Week 24 | -36.94 Score on a Scale | Standard Deviation 27.23 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Patient's Global Assessment of Arthritis, Using VAS Score | Week 4 | -30.21 Score on a Scale | Standard Deviation 27.47 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Patient's Global Assessment of Arthritis, Using VAS Score | Week 36 | -39.40 Score on a Scale | Standard Deviation 26.77 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Patient's Global Assessment of Arthritis, Using VAS Score | Week 12 | -35.63 Score on a Scale | Standard Deviation 26.19 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Patient's Global Assessment of Arthritis, Using VAS Score | Week 52 | -42.91 Score on a Scale | Standard Deviation 25.9 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Patient's Global Assessment of Arthritis, Using VAS Score | Week 8 | -32.67 Score on a Scale | Standard Deviation 26.85 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Patient's Global Assessment of Arthritis, Using VAS Score | Week 52 | -36.58 Score on a Scale | Standard Deviation 24.74 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Patient's Global Assessment of Arthritis, Using VAS Score | Week 8 | -28.79 Score on a Scale | Standard Deviation 23.07 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Patient's Global Assessment of Arthritis, Using VAS Score | Week 12 | -31.16 Score on a Scale | Standard Deviation 25.32 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Patient's Global Assessment of Arthritis, Using VAS Score | Week 24 | -31.76 Score on a Scale | Standard Deviation 25.09 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Patient's Global Assessment of Arthritis, Using VAS Score | Week 36 | -33.73 Score on a Scale | Standard Deviation 25.82 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Patient's Global Assessment of Arthritis, Using VAS Score | Week 4 | -26.03 Score on a Scale | Standard Deviation 24.5 |
Secondary
Change From Baseline in Physician's Global Assessment of Arthritis, Using VAS Score
Physician's assessment of participant's disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the physician's assessment of the participant's disease activity (0 mm=very good; 100 mm=very poor). Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest, where negative change from baseline indicated an improvement in physician-assessed disease activity.
Time frame: Weeks 4, 8, 12, 24, 36 and 52
Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were actually collected is indicated for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Physician's Global Assessment of Arthritis, Using VAS Score | Week 24 | -44.40 Score on a Scale | Standard Deviation 20.94 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Physician's Global Assessment of Arthritis, Using VAS Score | Week 8 | -39.29 Score on a Scale | Standard Deviation 20.3 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Physician's Global Assessment of Arthritis, Using VAS Score | Week 36 | -45.52 Score on a Scale | Standard Deviation 20.76 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Physician's Global Assessment of Arthritis, Using VAS Score | Week 4 | -37.07 Score on a Scale | Standard Deviation 20.75 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Physician's Global Assessment of Arthritis, Using VAS Score | Week 52 | -48.57 Score on a Scale | Standard Deviation 19.99 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Physician's Global Assessment of Arthritis, Using VAS Score | Week 12 | -42.23 Score on a Scale | Standard Deviation 20.2 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Physician's Global Assessment of Arthritis, Using VAS Score | Week 52 | -44.81 Score on a Scale | Standard Deviation 23.85 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Physician's Global Assessment of Arthritis, Using VAS Score | Week 4 | -30.65 Score on a Scale | Standard Deviation 24.09 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Physician's Global Assessment of Arthritis, Using VAS Score | Week 8 | -35.32 Score on a Scale | Standard Deviation 22.36 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Physician's Global Assessment of Arthritis, Using VAS Score | Week 12 | -37.37 Score on a Scale | Standard Deviation 22.14 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Physician's Global Assessment of Arthritis, Using VAS Score | Week 24 | -41.11 Score on a Scale | Standard Deviation 23.86 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Physician's Global Assessment of Arthritis, Using VAS Score | Week 36 | -43.13 Score on a Scale | Standard Deviation 24.14 |
Secondary
Change From Baseline in Simplified Disease Activity Index (SDAI)
Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity
Time frame: Weeks 4, 8, 12, 24, 36 and 52
Population: The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. Number of participants for whom data were actually collected is indicated for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 24 | -29.61 Score on a Scale | Standard Deviation 13.14 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 4 | -24.36 Score on a Scale | Standard Deviation 13.58 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 36 | -30.47 Score on a Scale | Standard Deviation 13.72 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 8 | -26.17 Score on a Scale | Standard Deviation 13.58 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 52 | -31.69 Score on a Scale | Standard Deviation 13.12 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 12 | -27.91 Score on a Scale | Standard Deviation 12.89 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 52 | -29.68 Score on a Scale | Standard Deviation 13.77 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 12 | -25.21 Score on a Scale | Standard Deviation 13.37 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 8 | -24.06 Score on a Scale | Standard Deviation 13.57 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 24 | -26.45 Score on a Scale | Standard Deviation 14.17 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 36 | -28.22 Score on a Scale | Standard Deviation 14.16 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 4 | -21.00 Score on a Scale | Standard Deviation 13.49 |
Secondary
Change From Baseline in Swollen Joint Count Based on 66 Joints
Swollen Joint Count: a total of 66 joints will be assessed for swelling. Each joint is assessed for the presence/absence of swelling. 66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. A negative change from Baseline indicated improvement.
Time frame: Weeks 4, 8, 12, 24, 36 and 52
Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were actually collected is indicated for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Swollen Joint Count Based on 66 Joints | Week 8 | -10.95 Score on a Scale | Standard Deviation 8.48 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Swollen Joint Count Based on 66 Joints | Week 24 | -11.93 Score on a Scale | Standard Deviation 8.33 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Swollen Joint Count Based on 66 Joints | Week 4 | -10.20 Score on a Scale | Standard Deviation 8.43 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Swollen Joint Count Based on 66 Joints | Week 36 | -12.15 Score on a Scale | Standard Deviation 8.57 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Swollen Joint Count Based on 66 Joints | Week 12 | -11.40 Score on a Scale | Standard Deviation 8.22 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Swollen Joint Count Based on 66 Joints | Week 52 | -12.17 Score on a Scale | Standard Deviation 8.55 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Swollen Joint Count Based on 66 Joints | Week 52 | -9.59 Score on a Scale | Standard Deviation 8.78 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Swollen Joint Count Based on 66 Joints | Week 4 | -7.85 Score on a Scale | Standard Deviation 6.71 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Swollen Joint Count Based on 66 Joints | Week 8 | -9.12 Score on a Scale | Standard Deviation 6.65 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Swollen Joint Count Based on 66 Joints | Week 12 | -9.08 Score on a Scale | Standard Deviation 6.84 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Swollen Joint Count Based on 66 Joints | Week 24 | -9.86 Score on a Scale | Standard Deviation 6.61 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Swollen Joint Count Based on 66 Joints | Week 36 | -9.98 Score on a Scale | Standard Deviation 6.96 |
Secondary
Change From Baseline in Tender/Painful Joint Count Based on 68 Joints
Tender Joint Count: a total of 68 joints will be assessed for tenderness. Each joint is assessed for the presence/absence of tenderness. 68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68. A negative change from Baseline indicated improvement.
Time frame: Weeks 4, 8, 12, 24, 36 and 52
Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were actually collected is indicated for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Tender/Painful Joint Count Based on 68 Joints | Week 24 | -17.96 Score on a Scale | Standard Deviation 12.24 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Tender/Painful Joint Count Based on 68 Joints | Week 12 | -16.55 Score on a Scale | Standard Deviation 12.39 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Tender/Painful Joint Count Based on 68 Joints | Week 36 | -18.48 Score on a Scale | Standard Deviation 12.77 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Tender/Painful Joint Count Based on 68 Joints | Week 8 | -16.11 Score on a Scale | Standard Deviation 12.45 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Tender/Painful Joint Count Based on 68 Joints | Week 52 | -18.70 Score on a Scale | Standard Deviation 12.99 |
| GDC-0853 (200mg BID) Cohort 1 | Change From Baseline in Tender/Painful Joint Count Based on 68 Joints | Week 4 | -15.02 Score on a Scale | Standard Deviation 12.38 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Tender/Painful Joint Count Based on 68 Joints | Week 52 | -17.73 Score on a Scale | Standard Deviation 11.88 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Tender/Painful Joint Count Based on 68 Joints | Week 4 | -13.23 Score on a Scale | Standard Deviation 12.27 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Tender/Painful Joint Count Based on 68 Joints | Week 12 | -15.99 Score on a Scale | Standard Deviation 12.03 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Tender/Painful Joint Count Based on 68 Joints | Week 24 | -16.65 Score on a Scale | Standard Deviation 11.35 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Tender/Painful Joint Count Based on 68 Joints | Week 36 | -17.51 Score on a Scale | Standard Deviation 11.6 |
| GDC-0853 (200mg BID) Cohort 2 | Change From Baseline in Tender/Painful Joint Count Based on 68 Joints | Week 8 | -15.19 Score on a Scale | Standard Deviation 12.59 |
Secondary
Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 CRP)
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6.
Time frame: Baseline, Weeks 4, 8, 12, 24, 36 and 52
Population: The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. Number of participants for whom data were actually collected is indicated for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 CRP) | Week 36 | 3.05 Score on a scale | Standard Deviation 1.05 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 CRP) | Week 12 | 3.37 Score on a scale | Standard Deviation 1.09 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 CRP) | Week 52 | 2.90 Score on a scale | Standard Deviation 1.03 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 CRP) | Baseline | 5.49 Score on a scale | Standard Deviation 0.85 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 CRP) | Week 4 | 3.64 Score on a scale | Standard Deviation 1.11 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 CRP) | Week 8 | 3.48 Score on a scale | Standard Deviation 1.06 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 CRP) | Week 24 | 3.16 Score on a scale | Standard Deviation 1.05 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 CRP) | Week 4 | 4.09 Score on a scale | Standard Deviation 1.19 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 CRP) | Week 24 | 3.55 Score on a scale | Standard Deviation 1.18 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 CRP) | Week 36 | 3.36 Score on a scale | Standard Deviation 1.06 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 CRP) | Week 8 | 3.81 Score on a scale | Standard Deviation 1.15 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 CRP) | Week 52 | 3.17 Score on a scale | Standard Deviation 1.28 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 CRP) | Week 12 | 3.73 Score on a scale | Standard Deviation 1.11 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 CRP) | Baseline | 5.59 Score on a scale | Standard Deviation 0.9 |
Secondary
Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 CRP)
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6.
Time frame: Baseline, Weeks 4, 8, 12, 24, 36 and 52
Population: The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. Number of participants for whom data were actually collected is indicated for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 CRP) | Baseline | 5.83 Score on a scale | Standard Deviation 0.88 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 CRP) | Week 36 | 3.06 Score on a scale | Standard Deviation 1.14 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 CRP) | Week 4 | 3.70 Score on a scale | Standard Deviation 1.19 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 CRP) | Week 8 | 3.53 Score on a scale | Standard Deviation 1.13 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 CRP) | Week 12 | 3.39 Score on a scale | Standard Deviation 1.14 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 CRP) | Week 24 | 3.18 Score on a scale | Standard Deviation 1.13 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 CRP) | Week 52 | 2.87 Score on a scale | Standard Deviation 1.09 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 CRP) | Week 12 | 3.81 Score on a scale | Standard Deviation 1.21 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 CRP) | Week 24 | 3.64 Score on a scale | Standard Deviation 1.27 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 CRP) | Week 8 | 3.92 Score on a scale | Standard Deviation 1.25 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 CRP) | Week 36 | 3.44 Score on a scale | Standard Deviation 1.21 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 CRP) | Baseline | 5.95 Score on a scale | Standard Deviation 0.94 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 CRP) | Week 52 | 3.22 Score on a scale | Standard Deviation 1.4 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 CRP) | Week 4 | 4.22 Score on a scale | Standard Deviation 1.34 |
Secondary
Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 ESR)
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6.
Time frame: Baseline, Weeks 4, 8, 12, 24, 36 and 52
Population: The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. Number of participants for whom data were actually collected is indicated for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 ESR) | Week 8 | 4.04 Score on a Scale | Standard Deviation 1.14 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 ESR) | Baseline | 6.17 Score on a Scale | Standard Deviation 0.79 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 ESR) | Week 4 | 4.25 Score on a Scale | Standard Deviation 1.16 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 ESR) | Week 12 | 3.89 Score on a Scale | Standard Deviation 1.16 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 ESR) | Week 24 | 3.65 Score on a Scale | Standard Deviation 1.08 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 ESR) | Week 36 | 3.46 Score on a Scale | Standard Deviation 1.15 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 ESR) | Week 52 | 3.35 Score on a Scale | Standard Deviation 1.14 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 ESR) | Week 24 | 4.15 Score on a Scale | Standard Deviation 1.27 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 ESR) | Week 8 | 4.51 Score on a Scale | Standard Deviation 1.17 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 ESR) | Week 36 | 3.96 Score on a Scale | Standard Deviation 1.15 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 ESR) | Week 12 | 4.40 Score on a Scale | Standard Deviation 1.11 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 ESR) | Baseline | 6.38 Score on a Scale | Standard Deviation 0.88 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 ESR) | Week 52 | 3.74 Score on a Scale | Standard Deviation 1.31 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 ESR) | Week 4 | 4.80 Score on a Scale | Standard Deviation 1.26 |
Secondary
Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 ESR)
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6.
Time frame: Baseline, Weeks 4, 8, 12, 24, 36 and 52
Population: The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. Number of participants for whom data were actually collected is indicated for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 ESR) | Week 8 | 4.04 Score on a Scale | Standard Deviation 1.23 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 ESR) | Week 24 | 3.62 Score on a Scale | Standard Deviation 1.16 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 ESR) | Week 12 | 3.87 Score on a Scale | Standard Deviation 1.23 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 ESR) | Week 36 | 3.43 Score on a Scale | Standard Deviation 1.24 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 ESR) | Week 4 | 4.27 Score on a Scale | Standard Deviation 1.25 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 ESR) | Week 52 | 3.27 Score on a Scale | Standard Deviation 1.2 |
| GDC-0853 (200mg BID) Cohort 1 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 ESR) | Baseline | 6.48 Score on a Scale | Standard Deviation 0.85 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 ESR) | Week 52 | 3.74 Score on a Scale | Standard Deviation 1.42 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 ESR) | Week 4 | 4.89 Score on a Scale | Standard Deviation 1.41 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 ESR) | Week 12 | 4.44 Score on a Scale | Standard Deviation 1.25 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 ESR) | Week 8 | 4.58 Score on a Scale | Standard Deviation 1.29 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 ESR) | Week 24 | 4.20 Score on a Scale | Standard Deviation 1.37 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 ESR) | Week 36 | 3.99 Score on a Scale | Standard Deviation 1.3 |
| GDC-0853 (200mg BID) Cohort 2 | Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 ESR) | Baseline | 6.71 Score on a Scale | Standard Deviation 0.96 |
Secondary
Minimum Plasma Concentration of GDC-0853 at Steady State (Ctrough,ss)
Population PK model estimated minimal plasma concentration (Ctrough) of GDC-0853 at steady-state (ss).
Time frame: Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination
Population: The PK-Evaluable population was defined as all participants that received any fenebrutinib/GDC-0853 and had sufficient data to enable estimation of key PK parameters. Participants who received incorrect therapy different from the intended therapy were summarized in the group according to the therapy actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Minimum Plasma Concentration of GDC-0853 at Steady State (Ctrough,ss) | 387 ng/mL | Standard Deviation 244 |
| GDC-0853 (200mg BID) Cohort 2 | Minimum Plasma Concentration of GDC-0853 at Steady State (Ctrough,ss) | 467 ng/mL | Standard Deviation 285 |
Secondary
Percentage of Participants Achieving ACR50 Response up to Week 12
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].
Time frame: Weeks 4, 8 and 12
Population: The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants Achieving ACR50 Response up to Week 12 | Week 4 | 37.1 Percentage |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants Achieving ACR50 Response up to Week 12 | Week 8 | 42.4 Percentage |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants Achieving ACR50 Response up to Week 12 | Week 12 | 45.6 Percentage |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants Achieving ACR50 Response up to Week 12 | Week 4 | 29.1 Percentage |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants Achieving ACR50 Response up to Week 12 | Week 8 | 34.9 Percentage |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants Achieving ACR50 Response up to Week 12 | Week 12 | 39.5 Percentage |
Secondary
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response
ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\]
Time frame: Weeks 4, 8, 12, 24, 36 and 52
Population: The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response | Week 52 | 75.4 Percentage |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response | Week 4 | 69.0 Percentage |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response | Week 24 | 75.4 Percentage |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response | Week 36 | 75.1 Percentage |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response | Week 8 | 72.9 Percentage |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response | Week 12 | 74.4 Percentage |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response | Week 52 | 68.6 Percentage |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response | Week 4 | 58.1 Percentage |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response | Week 8 | 68.6 Percentage |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response | Week 12 | 73.3 Percentage |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response | Week 24 | 72.1 Percentage |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response | Week 36 | 72.1 Percentage |
Secondary
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
ACR70 response is defined as a ≥ 70% improvement (reduction) compared with Baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].
Time frame: Weeks 4, 8, 12, 24, 36 and 52
Population: The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 8 | 21.7 Percentage |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 24 | 30.2 Percentage |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 4 | 19.8 Percentage |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 36 | 32.2 Percentage |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 52 | 36.3 Percentage |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 12 | 23.9 Percentage |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 52 | 27.9 Percentage |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 4 | 12.8 Percentage |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 8 | 17.4 Percentage |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 12 | 19.8 Percentage |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 24 | 20.9 Percentage |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Week 36 | 25.6 Percentage |
Secondary
Percentage of Participants With ACR/EULAR Remission
Assessed according to the Boolean based definition (tender joint count =\<1, swollen joint count =\<1, C-reactive Protein (CRP) =\<1, and patient global assessment =\<1)
Time frame: Weeks 4, 8, 12, 24, 36 and 52
Population: The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. Number of participants for whom data were actually collected is indicated for each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants With ACR/EULAR Remission | Week 24 | 13.0 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants With ACR/EULAR Remission | Week 4 | 5.0 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants With ACR/EULAR Remission | Week 8 | 7.8 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants With ACR/EULAR Remission | Week 12 | 7.4 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants With ACR/EULAR Remission | Week 36 | 15.6 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants With ACR/EULAR Remission | Week 52 | 17.8 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants With ACR/EULAR Remission | Week 8 | 5.9 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants With ACR/EULAR Remission | Week 24 | 6.0 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants With ACR/EULAR Remission | Week 52 | 10.7 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants With ACR/EULAR Remission | Week 36 | 11.4 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants With ACR/EULAR Remission | Week 4 | 5.8 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants With ACR/EULAR Remission | Week 12 | 7.2 Percentage of Participants |
Secondary
Percentage of Participants With Low Disease Activity (LDA) Based on DAS28
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. LDAS is defined as DAS28 ≤ 3.2
Time frame: Weeks 4, 8, 12, 24, 36 and 52
Population: The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants With Low Disease Activity (LDA) Based on DAS28 | Week 8 | 21.2 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants With Low Disease Activity (LDA) Based on DAS28 | Week 24 | 33.7 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants With Low Disease Activity (LDA) Based on DAS28 | Week 4 | 20.0 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants With Low Disease Activity (LDA) Based on DAS28 | Week 36 | 38.3 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants With Low Disease Activity (LDA) Based on DAS28 | Week 12 | 26.6 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants With Low Disease Activity (LDA) Based on DAS28 | Week 52 | 42.2 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants With Low Disease Activity (LDA) Based on DAS28 | Week 52 | 29.1 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants With Low Disease Activity (LDA) Based on DAS28 | Week 4 | 12.8 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants With Low Disease Activity (LDA) Based on DAS28 | Week 8 | 17.4 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants With Low Disease Activity (LDA) Based on DAS28 | Week 12 | 12.8 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants With Low Disease Activity (LDA) Based on DAS28 | Week 24 | 27.9 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants With Low Disease Activity (LDA) Based on DAS28 | Week 36 | 29.1 Percentage of Participants |
Secondary
Percentage of Participants With Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28)
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control.
Time frame: Weeks 4, 8, 12, 24, 36 and 52
Population: The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants With Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) | Week 52 | 25.6 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants With Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) | Week 4 | 8.8 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants With Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) | Week 8 | 10.7 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants With Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) | Week 12 | 13.9 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants With Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) | Week 24 | 17.8 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 1 | Percentage of Participants With Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) | Week 36 | 22.4 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants With Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) | Week 24 | 14.0 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants With Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) | Week 52 | 23.3 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants With Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) | Week 12 | 8.1 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants With Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) | Week 4 | 7.0 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants With Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) | Week 36 | 11.6 Percentage of Participants |
| GDC-0853 (200mg BID) Cohort 2 | Percentage of Participants With Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) | Week 8 | 8.1 Percentage of Participants |
Secondary
Plasma Decay Half-Life of GDC-0853 at Steady State (t1/2,ss)
Population PK model estimated plasma decay half life of GDC-0853 at steady-state.
Time frame: Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination
Population: The PK-Evaluable population was defined as all participants that received any fenebrutinib/GDC-0853 and had sufficient data to enable estimation of key PK parameters. Participants who received incorrect therapy different from the intended therapy were summarized in the group according to the therapy actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GDC-0853 (200mg BID) Cohort 1 | Plasma Decay Half-Life of GDC-0853 at Steady State (t1/2,ss) | 7.94 hr | Standard Deviation 3.16 |
| GDC-0853 (200mg BID) Cohort 2 | Plasma Decay Half-Life of GDC-0853 at Steady State (t1/2,ss) | 9.01 hr | Standard Deviation 4.9 |