Arthritis, Rheumatoid, Healthy
Conditions
Brief summary
To evaluate the safety and tolerability of multiple doses of BI 655064 administered subcutaneously in healthy volunteers (HVs) and in rheumatoid arthritis (RA) patients. To explore the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of multiple doses of BI 655064 in healthy volunteers (HVs) and rheumatoid arthritis (RA) patients. To assess clinical effect of BI 655064 in RA patients with prior inadequate response to methotrexate (MTX) after 12 weeks of treatment
Interventions
DRUGPlacebo matching BI 655064
Placebo matching BI 655064 injected subcutaneous.
DRUGBI 655064
BI 655064 injected subcutaneous
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
Part 1 (phase Ib) (HVs): 1. Healthy males and females according to the investigators assessment, as based on the following criteria: a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests 2. Age \>= 18 and \<= 60 years 3. Body Mass Index \>= 18.5 and \<= 29.9 kg/m2 4. Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation 5. Female subjects who meet any of the following criteria from at least 30 days before the first study drug administration and until 30 days after trial completion: * using adequate contraception, e.g. any of the following methods plus condom: implants, injectables, combined oral contraceptives, intrauterine device (IUD) * sexually abstinent * have a vasectomised sexual partner (vasectomy at least 1 year prior to enrolment) * surgically sterilised (including hysterectomy) * postmenopausal defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of follicle stimulating hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory) Part 2 (phase IIa) (RA Patients): 1. Age \>= 18 and \<= 70 years 2. Patients classified as having RA according to the 1987 ACR Classification Criteria 3. Inadequate clinical response to methotrexate monotherapy defined as moderate/high active disease after oral or s.c. MTX treatment given continuously for at least 3 months and for the last 6 weeks before screening at a stable weekly dose \>=15mg. For patients who do not tolerate the minimum weekly dose of at least 15 mg due to side effects, a stable weekly dose as low as 7.5 mg is also permitted. 4. DAS28 4v-CRP \>= 3.5 with \>= 6 tender and \>= 6 swollen joints out of 68/66 joint count at screening and confirmed by \>= 6 tender and \>= 6 swollen joints out of 68/66 joint count only at randomisation visit (Visit 2) 5. Serum CRP level \>= 0.8 mg/dL or ESR \>= 28 mm/1h at screening 6. Anti-CCP2 or Rheumatoid Factor positivity as per the limits of used assay at screening 7. Female patients who meet any of the following criteria from at least 30 days before the first study drug administration and until at least 6 months after last dose of MTX taken in the current trial: using adequate contraception, e.g. any of the following methods plus condom: implants, injectables, combined oral contraceptives, intrauterine device (IUD) * sexually abstinent * have a vasectomised sexual partner (vasectomy at least 1 year prior to enrolment) * surgically sterilised (including hysterectomy) * postmenopausal defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of follicle stimulating hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory) OR Male patients who: * are documented to be sterile or consistently and correctly use a condom while their female partners (if of childbearing potential) agree to use any of the following adequate contraception methods: implants, injectables, combined oral contraceptives, intrauterine device (IUD) from the date of screening until at least 6 months after the last dose of MTX taken in the current trial * don¿t donate any sperm sample for procreation purposes, from the date of screening until at least 6 months after last dose of MTX taken in the current trial. 8. Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation
Exclusion criteria
Part 1 (phase Ib in HVs): 1. Any finding in the medical examination (including BP, PR or ECG) deviating from normal and judged clinically relevant by the investigator 2. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance 3. Any evidence of a concomitant disease judged clinically relevant by the investigator 4. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 5. Diseases of the central nervous system (such as epilepsy), other neurological disorders or psychiatric disorders 6. History of relevant orthostatic hypotension, fainting spells, or blackouts 7. History of relevant allergy/hypersensitivity (including allergy to the trial medication or its excipients) 9\. Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial 12. Alcohol abuse (consumption of more than 140 g/week in females and 210 g/week in males) 13. Drug abuse or positive drug screen 17. Chronic or relevant acute infections, including but not limited to HIV, Hepatitis B and C and tuberculosis (including a history of clinical TB and/or a positive QuantiFERON TB-Gold test) 18. Subject is assessed by the investigator as unsuitable for inclusion e.g. considered not able to understand and comply with study requirements or has a condition that would not allow safe participation in the study 19. Positive pregnancy test, pregnancy or plans to become pregnant within 30 days after study completion 20. Lactation Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Cmax After the First and Last Dose | From first day of drug administration till end of trial, up to 77 days. Detailed PK can be found in the endpoint description. | Part 1: This outcome measure presents the maximum measured concentration of BI 655064 in plasma (Cmax) after the first and last (fourth) dose. More detailed time frame: Pharmacokinetic (PK) sample times: 0:30 hour (h) prior first administration of BI 655064 and 1 h, 8 h, 12 h, 24 h, 48 h, 72 h, 84 h, 96 h, 108 h, 120 h, 144 h, 167:30 h, 335:30 h, 503:30 h, 505 h, 516 h, 528 h, 552 h, 576 h, 600 h, 624 h, 648 h, 672 h, 696 h, 744 h, 816 h, 912 h, 1008 h, 1176 h, 1344 h, 1512 h, 1848 h thereafter; further administration times for BI 655064: 168 h, 336 h, and 504 h after first administration. |
| Part 1: AUC 0-infinity After the Last Dose | PK sample times: 1 h, 12 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 192 h, 240 h, 312 h, 408 h, 504 h, 672 h, 840 h, 1008 h, 1344 h after the last administration of BI 655064 on day 22 | Part 1: Area under the concentration-time curve of BI 655064 in plasma over the time interval from 0 extrapolated to infinite (AUC 0-infinity). |
| Part 1: AUCtau After the Last Dose | PK sample times: 1 h, 12 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 192 h, 240 h, 312 h, 408 h, 504 h, 672 h, 840 h, 1008 h, 1344 h after the last administration of trial drug on day 22 | Area under the concentration-time curve of BI 655064 in plasma after the 4th dose over a uniform dosing interval t (AUC t,4) after the first and 4th dose. AUCtau is synonymous with AUC0-168. |
| Part 1: Percentage of Subjects With Drug Related Adverse Events | from first administration of study medication (day 1) up to day 64 (dosing groups 80, 120, 180mg) or up to day 78 post-treatment (dosing group 240mg) | In Part 1 (Phase Ib): The primary safety endpoint was the percentage of subjects with AEs related to treatment with trial medication. |
| Part 2: American College of Rheumatology (ACR)20 Response Rate at Week 12 | at week 12 (day 85) from the initiation of study treatment | ACR 20 criteria at week 12 relative to the patient's status at baseline: that is, at least 20 percent (%) improvement in swollen joint count, at least 20% improvement in tender joint count, and at least 20% improvement in ≥3 of the following 5 variables: 1) patient's assessment of pain on the visual analogue scale (VAS), rated on a scale of 1 to 10; 2) patient's global assessment of disease on the VAS, rated on a scale of 1 to 10; 3) investigator's global assessment of disease on the VAS; 4) patient's assessment of disability on the health assessment questionnaire (HAQ), rated on a scale of 1 to 3; and 5) concentrations of acute phase reactants. For all scales (1-4): smaller values better. The ACR20 were evaluated descriptively. The data were analysed with a Bayesian approach using an informative prior for the placebo treatment group; predictive probability that the treatment difference was larger than 0%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40% or 45% was to be evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: ACR50 Response Rates at Week 12 | at week 12 (day 85) | ACR 50 criteria at week 12 relative to the patient's status at baseline: that is, at least 50 % improvement in swollen joint count, at least 50% improvement in tender joint count, and at least 50% improvement in ≥3 of the following 5 variables: 1) patient's assessment of pain on the visual analogue scale (VAS), rated on a scale of 1 to 10; 2) patient's global assessment of disease on the VAS, rated on a scale of 1 to 10; 3) investigator's global assessment of disease on the VAS; 4) patient's assessment of disability on the health assessment questionnaire (HAQ), rated on a scale of 1 to 3; and 5) concentrations of acute phase reactants. For all scales (1-4): smaller values better. The percentage of subjects with ACR50 response is presented. |
| Part 2: Change in DAS28-CRP Score at Week 12 | baseline (day 1) and week 12 (day 85) | Change at week 12 in the Disease activity score in 28 joints and C-reactive protein (DAS28-CRP) compared with the score at baseline. The mean was adjusted for region, anti-TNF history and baseline DAS28-CRP. DAS28-CRP is calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst), where the total score is calculated as follows: 0.56\*√(TJC) + 0.28\*√(SJC) + 0.36\*Ln(CRP+1) + 0.014\*VAS + 0.96. The total score ranges from 1.0 to 9.4, where a higher score indicates a better outcome. |
| Part 2: ACR70 Response Rates at Week 12 | at week 12 (day 85) | ACR70 criteria at week 12 relative to the patient's status at baseline: that is, at least 70 % improvement in swollen joint count, at least 70% improvement in tender joint count, and at least 70% improvement in ≥3 of the following 5 variables: 1) patient's assessment of pain on the visual analogue scale (VAS), rated on a scale of 1 to 10; 2) patient's global assessment of disease on the VAS, rated on a scale of 1 to 10; 3) investigator's global assessment of disease on the VAS; 4) patient's assessment of disability on the health assessment questionnaire (HAQ), rated on a scale of 1 to 3; and 5) concentrations of acute phase reactants. For all scales (1-4): smaller values better). The percentage of subjects with ACR50 response is presented. |
| Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | baseline (day 1) and week 12 (day 85) | Assessed by European League Against Rheumatism (EULAR) categorization as good, moderate, or nonresponders based on improvement from baseline using the DAS28-CRP at week 12. In this outcome measure the frequency of EULAR response rates (change from the day of first dose to the day of visit 14 in week 12) are presented. DAS28-CRP is calculated as 0.56\*√(TJC) + 0.28\*√(SJC) + 0.36\*Ln(CRP+1) + 0.014\*VAS + 0.96. The total score ranges from 1.0 to 9.4, where a higher score indicates a better outcome. EULAR response states were classified as follows: good responders were patients with an improvement of \>1.2 and a present score of ⩽3.2; moderate responders were patients with an improvement of \>0.6 to ⩽1.2 and a present score of ⩽5.1, or an improvement of \>1.2 and a present score of \>3.2; non-responders were any patients with an improvement of ⩽0.6, or patients with an improvement of \>0.6 to ⩽1.2 and a present score of \>5.1. Improvement (impr.) is abbreviated in the category names. |
| Part 2: EULAR DAS28-ESR at Week 12 | baseline (day 1) and week 12 (day 85) | Response as assessed by European League Against Rheumatism (EULAR) using Disease activity score in 28 joints and the erythrocyte sedimentation rate (DAS28-ESR) at week 12. In this outcome measure the frequency of EULAR response rates (change from the day of first dose to the day of visit 14 in week 12) are presented. DAS28-ESR is calculated as 0.56\*√(TJC) + 0.28\*√(SJC) + 0.70 \*Ln(ESR) + 0.014\*VAS. The total score ranges from 0 to 9.4, where a higher score indicates a better outcome. EULAR response states were classified as follows: good responders were patients with an improvement of \>1.2 and a present score of ⩽3.2; moderate responders were patients with an improvement of \>0.6 to ⩽1.2 and a present score of ⩽5.1, or an improvement of \>1.2 and a present score of \>3.2; non-responders were any patients with an improvement of ⩽0.6, or patients with an improvement of \>0.6 to ⩽1.2 and a present score of \>5.1. Improvement (impr.) is abbreviated in the category names. |
| Part 2: Percentage of Patients With a Decrease in DAS28-CRP of >1.2 at Week 12 | baseline (day 1) and week 12 (day 85) | Percentage of patients who had a decrease of \>1.2 on the Disease activity score in 28 joints and C-reactive protein (DAS28-CRP) at week 12 (day 85) compared to baseline. The adjusted absolute risk difference was adjusted for treatment, region and anti-TNF history. DAS28-CRP is calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst), where the total score is calculated as follows: 0.56\*√(TJC) + 0.28\*√(SJC) + 0.36\*Ln(CRP+1) + 0.014\*VAS + 0.96. The total score ranges from 1.0 to 9.4, where a higher score indicates a better outcome. |
Countries
Czechia, Germany, Netherlands, New Zealand, Poland, Spain
Participant flow
Recruitment details
Part 1 (Phase Ib multiple rising dose): 40 healthy volunteers were recruited, in 4 sequential groups of 10 subjects (8 of them received active drug, 2 placebo) each. Thereafter, part 2 (Phase 2a): 67 patients with Rheumatoid Arthritis(RA), who had prior inadequate response to Methotrexate (MTX)treatment, were randomised into 2 arms.
Pre-assignment details
All subjects were screened for eligibility to participate in trial. Subjects attended specialist sites to ensure that they (the subjects) met all implemented inclusion/exclusion criteria. Subjects were not to be randomised to trial drug if any of the specific entry criteria was violated.
Participants by arm
| Arm | Count |
|---|---|
| Part 1, Placebo BI 655064 80/120mg (HV) Part 1, Healthy volunteers (HV): Placebo matching BI 655064 80 or 120 milligram (mg) injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. | 4 |
| Part 1, Placebo BI 655064 180/240mg (HV) Part 1, Healthy volunteers (HV): Placebo matching BI 655064 180 or 240 mg injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks (180mg dosing group) or 8 weeks (240mg dosing group) follow-up period. | 4 |
| Part 1, BI 655064 80mg (HV) Part 1, Healthy volunteers (HV): 80 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. | 8 |
| Part 1, BI 655064 120mg (HV) Part 1, Healthy volunteers (HV): 120 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. | 8 |
| Part 1, BI 655064 180mg (HV) Part 1, Healthy volunteers (HV): 180 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. | 8 |
| Part 1, BI 655064 240mg (HV) Part 1, Healthy volunteers (HV): 240mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 8 weeks follow-up period. | 8 |
| Part 2, Placebo BI 655064 120mg (RA) Part 2, patients with Rheumatoid arthritis (RA) who had prior inadequate response to Methotrexat (MTX) therapy: Placebo matching BI 655064 120 milligram (mg) injected subcutaneous on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (once weekly for 12 weeks) followed by 8 weeks follow-up period. | 23 |
| Part 2, BI 655064 120mg (RA) Part 2, patients with RA who had prior inadequate response to MTX therapy: 120 milligram (mg) of BI 655064 injected subcutaneous on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (once weekly for 12 weeks) followed by 8 weeks follow-up period. | 44 |
| Total | 107 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 2 |
| Overall Study | Consent withdrawn | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Other reason not specified above | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1, Placebo BI 655064 80/120mg (HV) | Part 1, BI 655064 120mg (HV) | Part 1, BI 655064 80mg (HV) | Part 1, Placebo BI 655064 180/240mg (HV) | Total | Part 1, BI 655064 240mg (HV) | Part 1, BI 655064 180mg (HV) | Part 2, BI 655064 120mg (RA) | Part 2, Placebo BI 655064 120mg (RA) |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous Part 1 | 21.5 years STANDARD_DEVIATION 1.3 | 31.4 years STANDARD_DEVIATION 13.3 | 25.9 years STANDARD_DEVIATION 4.1 | 34.0 years STANDARD_DEVIATION 15.4 | 30.4 years STANDARD_DEVIATION 10.8 | 29.5 years STANDARD_DEVIATION 10.6 | 37.3 years STANDARD_DEVIATION 10.8 | — | — |
| Age, Continuous Part 2 | — | — | — | — | 54.2 years STANDARD_DEVIATION 11.8 | — | — | 53.7 years STANDARD_DEVIATION 13.3 | 55.1 years STANDARD_DEVIATION 8.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 5 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 7 Participants | 2 Participants | 3 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 7 Participants | 6 Participants | 2 Participants | 95 Participants | 6 Participants | 5 Participants | 43 Participants | 23 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 62 Participants | 1 Participants | 2 Participants | 37 Participants | 18 Participants |
| Sex: Female, Male Male | 4 Participants | 8 Participants | 6 Participants | 2 Participants | 45 Participants | 7 Participants | 6 Participants | 7 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 8 | 6 / 8 | 6 / 8 | 6 / 8 | 7 / 8 | 29 / 44 | 17 / 23 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 2 / 44 | 2 / 23 |
Outcome results
Primary
Part 1: AUC 0-infinity After the Last Dose
Part 1: Area under the concentration-time curve of BI 655064 in plasma over the time interval from 0 extrapolated to infinite (AUC 0-infinity).
Time frame: PK sample times: 1 h, 12 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 192 h, 240 h, 312 h, 408 h, 504 h, 672 h, 840 h, 1008 h, 1344 h after the last administration of BI 655064 on day 22
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, BI 655064 80mg (HV) | Part 1: AUC 0-infinity After the Last Dose | 3940 µg* hours (h)/mL | Geometric Coefficient of Variation 53.9 |
| Part 1, BI 655064 120mg (HV) | Part 1: AUC 0-infinity After the Last Dose | 11000 µg* hours (h)/mL | Geometric Coefficient of Variation 42.5 |
| Part 1, BI 655064 180mg (HV) | Part 1: AUC 0-infinity After the Last Dose | 19200 µg* hours (h)/mL | Geometric Coefficient of Variation 41.1 |
| Part 1, BI 655064 240mg (HV) | Part 1: AUC 0-infinity After the Last Dose | 39300 µg* hours (h)/mL | Geometric Coefficient of Variation 26.1 |
Comparison: Dose proportionality for AUC 0-infinity was explored after the last adminstration of BI 65564 on Day 22.95% CI: [1.6607, 2.3575]
Primary
Part 1: AUCtau After the Last Dose
Area under the concentration-time curve of BI 655064 in plasma after the 4th dose over a uniform dosing interval t (AUC t,4) after the first and 4th dose. AUCtau is synonymous with AUC0-168.
Time frame: PK sample times: 1 h, 12 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 192 h, 240 h, 312 h, 408 h, 504 h, 672 h, 840 h, 1008 h, 1344 h after the last administration of trial drug on day 22
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, BI 655064 80mg (HV) | Part 1: AUCtau After the Last Dose | 1790 µg*h/mL | Geometric Coefficient of Variation 56.4 |
| Part 1, BI 655064 120mg (HV) | Part 1: AUCtau After the Last Dose | 4140 µg*h/mL | Geometric Coefficient of Variation 35.4 |
| Part 1, BI 655064 180mg (HV) | Part 1: AUCtau After the Last Dose | 5470 µg*h/mL | Geometric Coefficient of Variation 37.4 |
| Part 1, BI 655064 240mg (HV) | Part 1: AUCtau After the Last Dose | 9460 µg*h/mL | Geometric Coefficient of Variation 22.4 |
Comparison: Dose proportionality for AUCtau was explored after the last administration of BI 65564 on Day 22.95% CI: [1.0876, 1.7574]
Primary
Part 1: Cmax After the First and Last Dose
Part 1: This outcome measure presents the maximum measured concentration of BI 655064 in plasma (Cmax) after the first and last (fourth) dose. More detailed time frame: Pharmacokinetic (PK) sample times: 0:30 hour (h) prior first administration of BI 655064 and 1 h, 8 h, 12 h, 24 h, 48 h, 72 h, 84 h, 96 h, 108 h, 120 h, 144 h, 167:30 h, 335:30 h, 503:30 h, 505 h, 516 h, 528 h, 552 h, 576 h, 600 h, 624 h, 648 h, 672 h, 696 h, 744 h, 816 h, 912 h, 1008 h, 1176 h, 1344 h, 1512 h, 1848 h thereafter; further administration times for BI 655064: 168 h, 336 h, and 504 h after first administration.
Time frame: From first day of drug administration till end of trial, up to 77 days. Detailed PK can be found in the endpoint description.
Population: All subjects were treated and and provided data for at least 1 primary pharmacokinetic (PK) endpoint and therefore all subjects were also included in the PK set (PKS).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1, BI 655064 80mg (HV) | Part 1: Cmax After the First and Last Dose | after the first dose | 1.59 microgram (µg)/ millilitre (mL) | Geometric Coefficient of Variation 492 |
| Part 1, BI 655064 80mg (HV) | Part 1: Cmax After the First and Last Dose | after the last (fourth) dose | 13.1 microgram (µg)/ millilitre (mL) | Geometric Coefficient of Variation 59.1 |
| Part 1, BI 655064 120mg (HV) | Part 1: Cmax After the First and Last Dose | after the last (fourth) dose | 28.7 microgram (µg)/ millilitre (mL) | Geometric Coefficient of Variation 35.6 |
| Part 1, BI 655064 120mg (HV) | Part 1: Cmax After the First and Last Dose | after the first dose | 7.70 microgram (µg)/ millilitre (mL) | Geometric Coefficient of Variation 29.5 |
| Part 1, BI 655064 180mg (HV) | Part 1: Cmax After the First and Last Dose | after the first dose | 9.87 microgram (µg)/ millilitre (mL) | Geometric Coefficient of Variation 67.8 |
| Part 1, BI 655064 180mg (HV) | Part 1: Cmax After the First and Last Dose | after the last (fourth) dose | 39.8 microgram (µg)/ millilitre (mL) | Geometric Coefficient of Variation 37.4 |
| Part 1, BI 655064 240mg (HV) | Part 1: Cmax After the First and Last Dose | after the first dose | 18.0 microgram (µg)/ millilitre (mL) | Geometric Coefficient of Variation 46.3 |
| Part 1, BI 655064 240mg (HV) | Part 1: Cmax After the First and Last Dose | after the last (fourth) dose | 68.4 microgram (µg)/ millilitre (mL) | Geometric Coefficient of Variation 21.9 |
Comparison: Dose proportionality for Cmax was explored after the first adminstration of BI 65564 on Day 1.95% CI: [1.1843, 2.9168]
Comparison: Dose proportionality for Cmax was explored after the last (fourth) adminstration of BI 65564 on Day 22.95% CI: [1.0869, 1.7584]
Primary
Part 1: Percentage of Subjects With Drug Related Adverse Events
In Part 1 (Phase Ib): The primary safety endpoint was the percentage of subjects with AEs related to treatment with trial medication.
Time frame: from first administration of study medication (day 1) up to day 64 (dosing groups 80, 120, 180mg) or up to day 78 post-treatment (dosing group 240mg)
Population: TS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1, BI 655064 80mg (HV) | Part 1: Percentage of Subjects With Drug Related Adverse Events | 50.0 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 1: Percentage of Subjects With Drug Related Adverse Events | 25.0 Percentage of participants |
| Part 1, BI 655064 180mg (HV) | Part 1: Percentage of Subjects With Drug Related Adverse Events | 12.5 Percentage of participants |
| Part 1, BI 655064 240mg (HV) | Part 1: Percentage of Subjects With Drug Related Adverse Events | 50.0 Percentage of participants |
| Part 1, BI 655064 240mg (HV) | Part 1: Percentage of Subjects With Drug Related Adverse Events | 0.0 Percentage of participants |
Primary
Part 2: American College of Rheumatology (ACR)20 Response Rate at Week 12
ACR 20 criteria at week 12 relative to the patient's status at baseline: that is, at least 20 percent (%) improvement in swollen joint count, at least 20% improvement in tender joint count, and at least 20% improvement in ≥3 of the following 5 variables: 1) patient's assessment of pain on the visual analogue scale (VAS), rated on a scale of 1 to 10; 2) patient's global assessment of disease on the VAS, rated on a scale of 1 to 10; 3) investigator's global assessment of disease on the VAS; 4) patient's assessment of disability on the health assessment questionnaire (HAQ), rated on a scale of 1 to 3; and 5) concentrations of acute phase reactants. For all scales (1-4): smaller values better. The ACR20 were evaluated descriptively. The data were analysed with a Bayesian approach using an informative prior for the placebo treatment group; predictive probability that the treatment difference was larger than 0%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40% or 45% was to be evaluated.
Time frame: at week 12 (day 85) from the initiation of study treatment
Population: The full analysis set (FAS) included 66 of 67 randomised and treated patients; 1 patient (placebo group) was excluded due to insufficient efficacy data (excluded due to important protocol violations). Noncompleters were assumed to be failures (NCF).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1, BI 655064 80mg (HV) | Part 2: American College of Rheumatology (ACR)20 Response Rate at Week 12 | 45.5 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: American College of Rheumatology (ACR)20 Response Rate at Week 12 | 68.2 Percentage of participants |
Comparison: Observed difference of ACR20 response for BI 120mg - Placebo
Comparison: Expected difference of ACR20 response for BI 120mg - Placebo
Comparison: Probability that difference of ACR20 response for BI 120mg - Placebo is larger than 0%
Comparison: Probability that difference of ACR20 response for BI 120mg - Placebo is larger than 5%
Comparison: Probability that difference of ACR20 response for BI 120mg - Placebo is larger than 10%
Comparison: Probability that difference of ACR20 response for BI 120mg - Placebo is larger than 15%
Comparison: Probability that difference of ACR20 response for BI 120mg - Placebo is larger than 20%
Comparison: Probability that difference of ACR20 response for BI 120mg - Placebo is larger than 25%
Comparison: Probability that difference of ACR20 response for BI 120mg - Placebo is larger than 30%
Comparison: Probability that difference of ACR20 response for BI 120mg - Placebo is larger than 35%
Comparison: Probability that difference of ACR20 response for BI 120mg - Placebo is larger than 40%
Comparison: Probability that difference of ACR20 response for BI 120mg - Placebo is larger than 45%
Secondary
Part 2: ACR50 Response Rates at Week 12
ACR 50 criteria at week 12 relative to the patient's status at baseline: that is, at least 50 % improvement in swollen joint count, at least 50% improvement in tender joint count, and at least 50% improvement in ≥3 of the following 5 variables: 1) patient's assessment of pain on the visual analogue scale (VAS), rated on a scale of 1 to 10; 2) patient's global assessment of disease on the VAS, rated on a scale of 1 to 10; 3) investigator's global assessment of disease on the VAS; 4) patient's assessment of disability on the health assessment questionnaire (HAQ), rated on a scale of 1 to 3; and 5) concentrations of acute phase reactants. For all scales (1-4): smaller values better. The percentage of subjects with ACR50 response is presented.
Time frame: at week 12 (day 85)
Population: FAS (NCF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1, BI 655064 80mg (HV) | Part 2: ACR50 Response Rates at Week 12 | unadjusted | 18.2 Percentage of participants |
| Part 1, BI 655064 80mg (HV) | Part 2: ACR50 Response Rates at Week 12 | adjusted | 15.6 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: ACR50 Response Rates at Week 12 | unadjusted | 36.4 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: ACR50 Response Rates at Week 12 | adjusted | 35.6 Percentage of participants |
Comparison: unadjustedp-value: 0.075495% CI: [-6.6, 38.6]One-sided exact test (see description)
Comparison: adjusted95% CI: [-4.6, 39]
Secondary
Part 2: ACR70 Response Rates at Week 12
ACR70 criteria at week 12 relative to the patient's status at baseline: that is, at least 70 % improvement in swollen joint count, at least 70% improvement in tender joint count, and at least 70% improvement in ≥3 of the following 5 variables: 1) patient's assessment of pain on the visual analogue scale (VAS), rated on a scale of 1 to 10; 2) patient's global assessment of disease on the VAS, rated on a scale of 1 to 10; 3) investigator's global assessment of disease on the VAS; 4) patient's assessment of disability on the health assessment questionnaire (HAQ), rated on a scale of 1 to 3; and 5) concentrations of acute phase reactants. For all scales (1-4): smaller values better). The percentage of subjects with ACR50 response is presented.
Time frame: at week 12 (day 85)
Population: FAS (NCF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1, BI 655064 80mg (HV) | Part 2: ACR70 Response Rates at Week 12 | unadjusted | 13.6 Percentage of participants |
| Part 1, BI 655064 80mg (HV) | Part 2: ACR70 Response Rates at Week 12 | adjusted | 13.0 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: ACR70 Response Rates at Week 12 | unadjusted | 18.2 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: ACR70 Response Rates at Week 12 | adjusted | 17.0 Percentage of participants |
Comparison: unadjustedp-value: 0.393895% CI: [-18.4, 22.3]one-sided exact test (see description)
Comparison: adjusted95% CI: [-18.9, 21.1]
Secondary
Part 2: Change in DAS28-CRP Score at Week 12
Change at week 12 in the Disease activity score in 28 joints and C-reactive protein (DAS28-CRP) compared with the score at baseline. The mean was adjusted for region, anti-TNF history and baseline DAS28-CRP. DAS28-CRP is calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst), where the total score is calculated as follows: 0.56\*√(TJC) + 0.28\*√(SJC) + 0.36\*Ln(CRP+1) + 0.014\*VAS + 0.96. The total score ranges from 1.0 to 9.4, where a higher score indicates a better outcome.
Time frame: baseline (day 1) and week 12 (day 85)
Population: FAS (last observation carried forward)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1, BI 655064 80mg (HV) | Part 2: Change in DAS28-CRP Score at Week 12 | Mean | -1.45 units on a scale | Standard Error 0.238 |
| Part 1, BI 655064 80mg (HV) | Part 2: Change in DAS28-CRP Score at Week 12 | Adjusted mean | -1.47 units on a scale | Standard Error 0.215 |
| Part 1, BI 655064 120mg (HV) | Part 2: Change in DAS28-CRP Score at Week 12 | Mean | -1.61 units on a scale | Standard Error 0.14 |
| Part 1, BI 655064 120mg (HV) | Part 2: Change in DAS28-CRP Score at Week 12 | Adjusted mean | -1.60 units on a scale | Standard Error 0.151 |
Comparison: difference calculated as BI 655064 120mg minus placebo.95% CI: [-0.67, 0.39]
Secondary
Part 2: EULAR DAS28-ESR at Week 12
Response as assessed by European League Against Rheumatism (EULAR) using Disease activity score in 28 joints and the erythrocyte sedimentation rate (DAS28-ESR) at week 12. In this outcome measure the frequency of EULAR response rates (change from the day of first dose to the day of visit 14 in week 12) are presented. DAS28-ESR is calculated as 0.56\*√(TJC) + 0.28\*√(SJC) + 0.70 \*Ln(ESR) + 0.014\*VAS. The total score ranges from 0 to 9.4, where a higher score indicates a better outcome. EULAR response states were classified as follows: good responders were patients with an improvement of \>1.2 and a present score of ⩽3.2; moderate responders were patients with an improvement of \>0.6 to ⩽1.2 and a present score of ⩽5.1, or an improvement of \>1.2 and a present score of \>3.2; non-responders were any patients with an improvement of ⩽0.6, or patients with an improvement of \>0.6 to ⩽1.2 and a present score of \>5.1. Improvement (impr.) is abbreviated in the category names.
Time frame: baseline (day 1) and week 12 (day 85)
Population: FAS (observed cases)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1, BI 655064 80mg (HV) | Part 2: EULAR DAS28-ESR at Week 12 | DAS28-ESR <=3.2, improvement (>0.6 and <=1.2) | 0.0 Percentage of participants |
| Part 1, BI 655064 80mg (HV) | Part 2: EULAR DAS28-ESR at Week 12 | DAS28-ESR (>3.2 and <=5.1), improvement <=0.6 | 0.0 Percentage of participants |
| Part 1, BI 655064 80mg (HV) | Part 2: EULAR DAS28-ESR at Week 12 | DAS28-ESR (>3.2 and <=5.1), improvement >1.2 | 42.1 Percentage of participants |
| Part 1, BI 655064 80mg (HV) | Part 2: EULAR DAS28-ESR at Week 12 | DAS28-ESR >5.1, improvement >1.2 | 21.1 Percentage of participants |
| Part 1, BI 655064 80mg (HV) | Part 2: EULAR DAS28-ESR at Week 12 | DAS28-ESR <=3.2, improvement <=0.6 | 0.0 Percentage of participants |
| Part 1, BI 655064 80mg (HV) | Part 2: EULAR DAS28-ESR at Week 12 | DAS28-ESR >5.1, improvement (>0.6 and <=1.2) | 5.3 Percentage of participants |
| Part 1, BI 655064 80mg (HV) | Part 2: EULAR DAS28-ESR at Week 12 | DAS28-ESR (>3.2 and <=5.1), impr. (>0.6 and <=1.2) | 5.3 Percentage of participants |
| Part 1, BI 655064 80mg (HV) | Part 2: EULAR DAS28-ESR at Week 12 | DAS28-ESR >5.1, improvement <=0.6 | 15.8 Percentage of participants |
| Part 1, BI 655064 80mg (HV) | Part 2: EULAR DAS28-ESR at Week 12 | DAS28-ESR <=3.2, improvement >1.2 | 10.5 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: EULAR DAS28-ESR at Week 12 | DAS28-ESR >5.1, improvement <=0.6 | 5.1 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: EULAR DAS28-ESR at Week 12 | DAS28-ESR <=3.2, improvement >1.2 | 20.5 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: EULAR DAS28-ESR at Week 12 | DAS28-ESR <=3.2, improvement (>0.6 and <=1.2) | 0.0 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: EULAR DAS28-ESR at Week 12 | DAS28-ESR <=3.2, improvement <=0.6 | 0.0 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: EULAR DAS28-ESR at Week 12 | DAS28-ESR (>3.2 and <=5.1), improvement >1.2 | 51.3 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: EULAR DAS28-ESR at Week 12 | DAS28-ESR (>3.2 and <=5.1), impr. (>0.6 and <=1.2) | 5.1 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: EULAR DAS28-ESR at Week 12 | DAS28-ESR (>3.2 and <=5.1), improvement <=0.6 | 0.0 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: EULAR DAS28-ESR at Week 12 | DAS28-ESR >5.1, improvement >1.2 | 10.3 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: EULAR DAS28-ESR at Week 12 | DAS28-ESR >5.1, improvement (>0.6 and <=1.2) | 7.7 Percentage of participants |
Secondary
Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12
Assessed by European League Against Rheumatism (EULAR) categorization as good, moderate, or nonresponders based on improvement from baseline using the DAS28-CRP at week 12. In this outcome measure the frequency of EULAR response rates (change from the day of first dose to the day of visit 14 in week 12) are presented. DAS28-CRP is calculated as 0.56\*√(TJC) + 0.28\*√(SJC) + 0.36\*Ln(CRP+1) + 0.014\*VAS + 0.96. The total score ranges from 1.0 to 9.4, where a higher score indicates a better outcome. EULAR response states were classified as follows: good responders were patients with an improvement of \>1.2 and a present score of ⩽3.2; moderate responders were patients with an improvement of \>0.6 to ⩽1.2 and a present score of ⩽5.1, or an improvement of \>1.2 and a present score of \>3.2; non-responders were any patients with an improvement of ⩽0.6, or patients with an improvement of \>0.6 to ⩽1.2 and a present score of \>5.1. Improvement (impr.) is abbreviated in the category names.
Time frame: baseline (day 1) and week 12 (day 85)
Population: FAS (observed cases)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1, BI 655064 80mg (HV) | Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | DAS28-CRP <=3.2, improvement <=0.6 | 0.0 Percentage of participants |
| Part 1, BI 655064 80mg (HV) | Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | DAS28-CRP >5.1, improvement >1.2 | 10.0 Percentage of participants |
| Part 1, BI 655064 80mg (HV) | Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | DAS28-CRP (>3.2 and <=5.1), impr. (>0.6 and <=1.2) | 5.0 Percentage of participants |
| Part 1, BI 655064 80mg (HV) | Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | DAS28-CRP>5.1, improvement (>0.6 and <=1.2) | 10.0 Percentage of participants |
| Part 1, BI 655064 80mg (HV) | Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | DAS28-CRP (>3.2 and <=5.1), improvement >1.2 | 25.0 Percentage of participants |
| Part 1, BI 655064 80mg (HV) | Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | DAS28-CRP >5.1, improvement <=0.6 | 10.0 Percentage of participants |
| Part 1, BI 655064 80mg (HV) | Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | DAS28-CRP (>3.2 and <=5.1), improvement <=0.6 | 10.0 Percentage of participants |
| Part 1, BI 655064 80mg (HV) | Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | DAS28-CRP <=3.2, improvement >1.2 | 25.0 Percentage of participants |
| Part 1, BI 655064 80mg (HV) | Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | DAS28-CRP <=3.2, improvement (>0.6 and <=1.2) | 5.0 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | DAS28-CRP <=3.2, improvement >1.2 | 35.9 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | DAS28-CRP <=3.2, improvement (>0.6 and <=1.2) | 2.6 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | DAS28-CRP <=3.2, improvement <=0.6 | 0.0 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | DAS28-CRP (>3.2 and <=5.1), improvement >1.2 | 35.9 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | DAS28-CRP (>3.2 and <=5.1), impr. (>0.6 and <=1.2) | 7.7 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | DAS28-CRP (>3.2 and <=5.1), improvement <=0.6 | 2.6 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | DAS28-CRP >5.1, improvement >1.2 | 0.0 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | DAS28-CRP>5.1, improvement (>0.6 and <=1.2) | 7.7 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | DAS28-CRP >5.1, improvement <=0.6 | 7.7 Percentage of participants |
Secondary
Part 2: Percentage of Patients With a Decrease in DAS28-CRP of >1.2 at Week 12
Percentage of patients who had a decrease of \>1.2 on the Disease activity score in 28 joints and C-reactive protein (DAS28-CRP) at week 12 (day 85) compared to baseline. The adjusted absolute risk difference was adjusted for treatment, region and anti-TNF history. DAS28-CRP is calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst), where the total score is calculated as follows: 0.56\*√(TJC) + 0.28\*√(SJC) + 0.36\*Ln(CRP+1) + 0.014\*VAS + 0.96. The total score ranges from 1.0 to 9.4, where a higher score indicates a better outcome.
Time frame: baseline (day 1) and week 12 (day 85)
Population: FAS (Last observation carried forward)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1, BI 655064 80mg (HV) | Part 2: Percentage of Patients With a Decrease in DAS28-CRP of >1.2 at Week 12 | Unadjusted | 59.1 Percentage of participants |
| Part 1, BI 655064 80mg (HV) | Part 2: Percentage of Patients With a Decrease in DAS28-CRP of >1.2 at Week 12 | Adjusted | 58.2 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: Percentage of Patients With a Decrease in DAS28-CRP of >1.2 at Week 12 | Unadjusted | 65.9 Percentage of participants |
| Part 1, BI 655064 120mg (HV) | Part 2: Percentage of Patients With a Decrease in DAS28-CRP of >1.2 at Week 12 | Adjusted | 67.1 Percentage of participants |
Comparison: unadjusted95% CI: [-17.6, 32.7]
Comparison: adjusted95% CI: [-15.9, 34.2]