Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
GDC-0853 · 9 trials · 7 indications
The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. The maximum UAS7 value is 42. A higher score indicates worse disease. A negative change score (Day 57 score minus Baseline score) indicates improvement.
The Systemic Lupus Erythematosus Responder Index (SRI)-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[10 mm\] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity.
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.
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 \[either C-reactive protein or Erythrocyte Sedimentation Rate\].
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 \[either C-reactive protein or Erythrocyte Sedimentation Rate\].
An Adverse event 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. A SAE was any experience that suggested a significant hazard, contraindication, side effect or precaution that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant.
Cmax for midazolam (Part 1), rosuvastatin (Part 2), and simvastatin (Part 3) in the presence and absence of GDC-0853 and Cmax for GDC-0853 (Part 4) in the presence and absence of itraconazole.
AUC0-t for midazolam (Part 1), rosuvastatin (Part 2), and simvastatin (Part 3) in the presence and absence of GDC-0853 and AUC0-t for GDC-0853 (Part 4) in the presence and absence of itraconazole.
An AE is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Preexisting conditions which worsen during a study are also considered as adverse events. A SAE is any untoward medical occurrence that at any dose: results in death, or is life-threatening, or requires inpatient hospitalization or prolongation of existing hospitalization, or results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. The term "life-threatening" in the definition of "serious" refers to an event in which the patient was at risk of death at the time of the event, not an event which hypothetically might have caused death if it were more severe.
Number of participants with clinical significant change in vital sign, physical examination findings, clinical laboratory results and electrocardiograms (ECGs) will be reported.
| Arm | Type | Description |
|---|---|---|
| Cohort 1: Placebo | PLACEBO_COMPARATOR | Participants received matching placebo twice daily from Day 1 to 56. |
| Cohort 1: GDC-0853 200mg BID | EXPERIMENTAL | Participants received GDC-0853 200mg twice daily from Day 1 to 56. |
| Cohort 2: Placebo | PLACEBO_COMPARATOR | Participants received matching placebo up to twice daily from Day 1 to 56. |
| Cohort 2: GDC-0853 50mg QD | EXPERIMENTAL | Participants received GDC-0853 50mg once daily from Day 1 to 56. |
| Cohort 2: GDC-0853 150mg QD | EXPERIMENTAL | Participants received GDC-0853 150mg once daily from Day 1 to 56. |
| Cohort 2: GDC-0853 200mg BID | EXPERIMENTAL | Participants received GDC-0853 200mg twice daily from Day 1 to 56. |
| Placebo | PLACEBO_COMPARATOR | Participants received matching placebo to GDC-0853 orally starting on Day 1 and ending at Week 48, in combination with background standard of care therapy. |
| GDC-0853 (150mg) QD | EXPERIMENTAL | Participants received GDC-0853 (150mg) orally once daily (QD) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy. |
| GDC-0853 (200mg) BID | EXPERIMENTAL | Participants received GDC-0853 (200mg) orally twice daily (BID) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy. |
| GDC-0853 (200mg BID) Cohort 1 | EXPERIMENTAL | 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. |
| GDC-0853 (200mg BID) Cohort 2 | EXPERIMENTAL | 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. |
| Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | EXPERIMENTAL | Participants of Cohort 1 will receive GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
| Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | EXPERIMENTAL | Participants of Cohort 1 will receive GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
| Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | EXPERIMENTAL | Participants of Cohort 1 will receive GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
| Cohort 1: GDC-0853 Placebo + Adalimumab | ACTIVE_COMPARATOR | Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
| Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | PLACEBO_COMPARATOR | Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
| Cohort 2: GDC-0853 High Dose | EXPERIMENTAL | Participants of Cohort 2 will receive GDC-0853 high dose, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
| Cohort 2: GDC-0853 Placebo | PLACEBO_COMPARATOR | Participants of Cohort 2 will receive placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
| Part 1 | EXPERIMENTAL | Participants will receive a single dose of midazolam followed by multiple doses of GDC-0853 coadministered with a single dose of midazolam. |
| Part 2 | EXPERIMENTAL | Participants will receive a single dose of rosuvastatin followed by multiple doses of GDC-0853 coadministered with a single dose of rosuvastatin. |
| Part 3 | EXPERIMENTAL | Participants will receive a single dose of simvastatin followed by multiple doses of GDC-0853 coadministered with a single dose of simvastatin. |
| Part 4 | EXPERIMENTAL | Participants will receive a single dose of GDC-0853 followed by multiple doses of itraconazole coadministered with a single dose of GDC-0853. |
| Part 1: GDC-0853 (Effect of Formulation) | EXPERIMENTAL | Participants will receive five single oral doses of test formulations of GDC-0853 co-administered with rabeprazole in the fasted state. |
| Part 2: GDC-0853 (Effect of Food and Rabeprazole) | EXPERIMENTAL | Participants will receive three single oral doses of one GDC-0853 formulations selected from Part 1 of this study. One dose will be administered in the fasted state, one dose will be administered in the fed state, and one dose will be co-administered with rabeprazole in the fed or fasted state, depending on randomization. |
| Part 3: GDC-0853 Optimized (Effect of Food and Rabeprazole) | EXPERIMENTAL | Participants will receive three single oral doses of an optimized tablet formulations of GDC-0853. One dose will be administered in the fasted state, one dose will be administered in the fed state, and one dose will be co-administered with rabeprazole in the fed or fasted state, depending on randomization. |
| Cohort 1: GDC-0853 Low Dose | EXPERIMENTAL | Japanese subjects will receive a single low dose of GDC-0853 or matching placebo by mouth. |
| Cohort 2: GDC-0853 Intermediate Dose | EXPERIMENTAL | Japanese subjects will receive a single intermediate dose of GDC-0853 or matching placebo by mouth. Subsequently, participants will receive twice-daily intermediate doses of GDC-0853 or matching placebo by mouth for 4 days followed by a single intermediate dose of GDC-0853 or matching placebo by mouth. |
| Cohort 3: GDC-0853 Intermediate Dose | EXPERIMENTAL | Caucasian subjects will receive a single intermediate dose of GDC-0853 or matching placebo by mouth. Subsequently, participants will receive twice-daily intermediate doses of GDC-0853 or matching placebo by mouth for 4 days followed by a single intermediate dose of GDC-0853 or matching placebo by mouth. |
| Cohort 4: GDC-0853 Low Dose | EXPERIMENTAL | Japanese subjects will receive a single high dose of GDC-0853 or matching placebo by mouth. |
| Part 1: GDC-0853, Rabeprazole (Fasting State) | EXPERIMENTAL | Participants will receive single dose of GDC-0853 (200 milligrams \[mg\]) in a crossover design as either the capsule or tablet formulation in the fasted state with the final fixed treatment consisting of the tablet formulation administered in the fasted state after prior administration of rabeprazole (20 mg twice daily \[BID\]) for 3 days. |
| Part 2: GDC-0853, Rabeprazole (Fasting or Fed State) | EXPERIMENTAL | Participants will receive single dose of GDC-0853 (200 mg) tablet formulation in the fasted or fed state in a crossover design with the final fixed treatment consisting of the tablet formulation administered in the fed state after prior administration of rabeprazole (20 mg BID) for 3 days. |
| Part 3: GDC-0853, Methotrexate | EXPERIMENTAL | Participants will receive single dose of methotrexate (7.5 mg) under fasting conditions on Day 1 (5 mg folic acid will be administered the following day \[Day 2\]) and then GDC-0853 (200 mg) tablet formulation twice daily (BID) under fasting conditions (an overnight fast for the morning dose and a 2 hour fast for the evening dose) from Days 15 to 20 after washout period from Days 2 to 14. On Day 21, participants will receive single dose of methotrexate (7.5 mg) with single dose of GDC-0853 (200 mg) tablet formulation under fasting conditions, and folic acid (5 mg) will be administered on Day 22. |
| Dose-escalation | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| GDC-0853 | DRUG | GDC-0853 will be administered orally at dosages of 50, 150 and 200mg to participants, as per the dosing schedules described above. |
| Placebo | DRUG | Matching Placebo will be administered orally, as per the dosing schedules described above. |
| Adalimumab | DRUG | Participants will receive adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. |
| Folic Acid | DRUG | Participants will receive stable background therapy of folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
| MTX | DRUG | Participants will receive stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines). |
| Midazolam | DRUG | Single dose midazolam |
| Midazolam and GDC-0853 | DRUG | Multiple doses GDC-0853 and single dose midazolam |
| Rosuvastatin | DRUG | Single dose rosuvastatin |
| Rosuvastatin and GDC-0853 | DRUG | Multiple doses GDC-0853 and single dose rosuvastatin |
| Simvastatin | DRUG | Single dose simvastatin |
| Simvastatin and GDC-0853 | DRUG | Multiple doses GDC-0853 and single dose simvastatin |
| Itraconazole | DRUG | Multiple doses itraconazole for 6 days |
| GDC-0853 and itraconazole | DRUG | Multiple doses itraconazole and single dose GDC-0853 |
| Rabeprazole | DRUG | Participants will receive rabeprazole 20 mg twice daily (BID) for three days prior to GDC-0853 administration and a single dose coadministered with GDC-0853. |
| Methotrexate | DRUG | Methotrexate will be administered orally as tablet at a single dose of 7.5 mg. |
Inclusion Criteria: * Aged 18-75 years, inclusive * Diagnosis of chronic spontaneous urticaria (CSU) refractory to H1 antihistamines at the time of randomization * Willing and able to complete an Urticaria Participant Daily eDiary for the duration of the study * No evidence of active or latent or i...
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GDC-0853 is an investigational small molecule being studied for rheumatoid arthritis, refractory chronic spontaneous urticaria, and as a healthy volunteer drug in drug-drug interaction studies. It has been evaluated in Phase 1 and Phase 2 clinical trials, but it is not approved and remains in clinical development.
GDC-0853 is being developed by Roche Holding AG, which trades under the ticker RHHBY. The company has sponsored clinical trials of the drug in multiple countries, including the United States, Argentina, Brazil, and several European and Asian nations.
GDC-0853 has completed Phase 1 and Phase 2 clinical trials. It is an investigational drug and has not received FDA approval. All trials listed for GDC-0853 are completed, with no active trials currently ongoing.
GDC-0853 has been studied in four completed clinical trials. These include NCT02833350 and NCT02983227 for rheumatoid arthritis, NCT03137069 for refractory chronic spontaneous urticaria, and NCT03174041, a drug-drug interaction study in healthy participants. The trials enrolled a total of 1,074 participants.
GDC-0853 is also known as fenebrutinib. It is an investigational small molecule being developed by Roche for autoimmune conditions such as rheumatoid arthritis and chronic spontaneous urticaria. The drug has completed Phase 2 trials but is not yet approved.