Trial Outcomes & Findings for BI 695501 Compared to Adalimumab in Patients With Active Rheumatoid Arthritis (NCT NCT02137226)
NCT ID: NCT02137226
Last Updated: 2018-01-19
Results Overview
The proportion of patients meeting the ACR20 response criteria was assessed. A patient had an ACR20 response if all of the following occurred: A ≥ 20 % improvement in the swollen joint count (66 joints), A ≥ 20 % improvement in the tender joint count (68 joints), A ≥ 20 % improvement in at least three of the following assessments: Patient's assessment of pain, Patient's global assessment of disease activity (equivalent to the General Health component of the Disease Activity Score (DAS)), Physician's global assessment of disease activity, Patient's assessment of physical function, as measured by the Health Assessment Questionnaire - Disability Index (HAQ-DI) Acute phase reactant (C-reactive protein (CRP)).The Full Analysis Set contained all enrolled patients who were randomized to trial drug and who received at least one dose of trial drug and had all efficacy measures relevant for the co-primary efficacy endpoints measured at baseline and at least once post- baseline.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
645 participants
Primary outcome timeframe
Week 12
Results posted on
2018-01-19
Participant Flow
A randomized, double-blind, parallel arm, multiple dose, active comparator trial to assess efficacy, safety and immunogenicity of BI 695501 versus adalimumab in patients with active rheumatoid arthritis. Patient received background methotrexate (MTX) treatment.
One patient was initially treated with Humira and discontinued prior to Week 24. This patient was mistakenly re randomized to BI 695501 but not treated. For safety set this was counted in Humira not re-randomized group (as treated), and for other analysis sets, this patient was counted in the Humira to BI 695501 group (as randomized).
Participant milestones
| Measure |
BI 695501
Each patient received 40 milligram (mg)/0.8 millilitre (mL) BI 695501 solution for injection, administered by subcutaneous (SC) injection every 2 weeks up to and including the first 22 weeks of treatment (Period 1).
|
US-licensed Humira®
Each patient received 40 mg/0.8 mL US-licenced Humira® solution for injection, administered by SC injection every 2 weeks up to and including the first 22 weeks of treatment (Period 1).
|
BI 695501 to BI 695501
Patients initially randomized to BI 695501 in Period 1 and re-randomized to BI 695501 in Period 2. Each patient received 40 mg/0.8 mL BI 695501 solution for injection, administered by SC injection every 2 weeks from Week 24 to Week 48.
|
US-licensed Humira® to US-licensed Humira®
Patients initially randomized to US-licensed Humira® in Period 1 and re-randomized to US-licensed Humira® in Period 2. Each patient received 40 mg/0.8 mL US-licenced Humira® solution for injection, administered by SC injection every 2 weeks from Week 24 to Week 48.
|
US-licensed Humira® to BI 695501
Patients initially randomized to US-licensed Humira® in Period 1 and re-randomized to BI 695501 in Period 2. Each patient received 40 mg/0.8 mL US-licenced Humira® in period 1 and 40 mg/0.8 mL BI 695501 solution for injection, administered by SC injection every 2 weeks from Week 24 to Week 48.
|
|---|---|---|---|---|---|
|
Period 1 (Initial Randomization)
STARTED
|
324
|
321
|
0
|
0
|
0
|
|
Period 1 (Initial Randomization)
COMPLETED
|
304
|
305
|
0
|
0
|
0
|
|
Period 1 (Initial Randomization)
NOT COMPLETED
|
20
|
16
|
0
|
0
|
0
|
|
Period 2 (Re - Randomization)
STARTED
|
0
|
0
|
298
|
148
|
147
|
|
Period 2 (Re - Randomization)
COMPLETED
|
0
|
0
|
281
|
140
|
138
|
|
Period 2 (Re - Randomization)
NOT COMPLETED
|
0
|
0
|
17
|
8
|
9
|
Reasons for withdrawal
| Measure |
BI 695501
Each patient received 40 milligram (mg)/0.8 millilitre (mL) BI 695501 solution for injection, administered by subcutaneous (SC) injection every 2 weeks up to and including the first 22 weeks of treatment (Period 1).
|
US-licensed Humira®
Each patient received 40 mg/0.8 mL US-licenced Humira® solution for injection, administered by SC injection every 2 weeks up to and including the first 22 weeks of treatment (Period 1).
|
BI 695501 to BI 695501
Patients initially randomized to BI 695501 in Period 1 and re-randomized to BI 695501 in Period 2. Each patient received 40 mg/0.8 mL BI 695501 solution for injection, administered by SC injection every 2 weeks from Week 24 to Week 48.
|
US-licensed Humira® to US-licensed Humira®
Patients initially randomized to US-licensed Humira® in Period 1 and re-randomized to US-licensed Humira® in Period 2. Each patient received 40 mg/0.8 mL US-licenced Humira® solution for injection, administered by SC injection every 2 weeks from Week 24 to Week 48.
|
US-licensed Humira® to BI 695501
Patients initially randomized to US-licensed Humira® in Period 1 and re-randomized to BI 695501 in Period 2. Each patient received 40 mg/0.8 mL US-licenced Humira® in period 1 and 40 mg/0.8 mL BI 695501 solution for injection, administered by SC injection every 2 weeks from Week 24 to Week 48.
|
|---|---|---|---|---|---|
|
Period 1 (Initial Randomization)
Adverse Event
|
3
|
3
|
0
|
0
|
0
|
|
Period 1 (Initial Randomization)
Withdrawal by Subject
|
11
|
5
|
0
|
0
|
0
|
|
Period 1 (Initial Randomization)
Physician Decision
|
1
|
3
|
0
|
0
|
0
|
|
Period 1 (Initial Randomization)
Lost to Follow-up
|
3
|
2
|
0
|
0
|
0
|
|
Period 1 (Initial Randomization)
Lack of Efficacy
|
1
|
0
|
0
|
0
|
0
|
|
Period 1 (Initial Randomization)
Other Reason
|
1
|
3
|
0
|
0
|
0
|
|
Period 2 (Re - Randomization)
Adverse Event
|
0
|
0
|
3
|
1
|
4
|
|
Period 2 (Re - Randomization)
Withdrawal by Subject
|
0
|
0
|
8
|
5
|
4
|
|
Period 2 (Re - Randomization)
Physician Decision
|
0
|
0
|
0
|
1
|
0
|
|
Period 2 (Re - Randomization)
Lost to Follow-up
|
0
|
0
|
3
|
0
|
0
|
|
Period 2 (Re - Randomization)
Lack of Efficacy
|
0
|
0
|
2
|
0
|
0
|
|
Period 2 (Re - Randomization)
Other Reason
|
0
|
0
|
1
|
1
|
1
|
Baseline Characteristics
BI 695501 Compared to Adalimumab in Patients With Active Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
BI 695501
n=324 Participants
Each patient received 40 milligram (mg)/0.8 millilitre (mL) BI 695501 solution for injection, administered by subcutaneous (SC) injection every 2 weeks up to and including the first 22 weeks of treatment (Period 1).
|
US-licensed Humira®
n=321 Participants
Each patient received 40 mg/0.8 mL US-licenced Humira® solution for injection, administered by SC injection every 2 weeks up to and including the first 22 weeks of treatment (Period 1).
|
Total
n=645 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53.7 Years
STANDARD_DEVIATION 12.04 • n=99 Participants
|
53.6 Years
STANDARD_DEVIATION 11.32 • n=107 Participants
|
53.6 Years
STANDARD_DEVIATION 11.68 • n=206 Participants
|
|
Sex: Female, Male
Female
|
267 Participants
n=99 Participants
|
269 Participants
n=107 Participants
|
536 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
57 Participants
n=99 Participants
|
52 Participants
n=107 Participants
|
109 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Week 12Population: Full Analysis Set. Patients who discontinued treatment prior to the time-point had their binary response imputed as non-responder, a method commonly known as non-responder imputation. For truly missing data at the component level, multiple imputation was used.
The proportion of patients meeting the ACR20 response criteria was assessed. A patient had an ACR20 response if all of the following occurred: A ≥ 20 % improvement in the swollen joint count (66 joints), A ≥ 20 % improvement in the tender joint count (68 joints), A ≥ 20 % improvement in at least three of the following assessments: Patient's assessment of pain, Patient's global assessment of disease activity (equivalent to the General Health component of the Disease Activity Score (DAS)), Physician's global assessment of disease activity, Patient's assessment of physical function, as measured by the Health Assessment Questionnaire - Disability Index (HAQ-DI) Acute phase reactant (C-reactive protein (CRP)).The Full Analysis Set contained all enrolled patients who were randomized to trial drug and who received at least one dose of trial drug and had all efficacy measures relevant for the co-primary efficacy endpoints measured at baseline and at least once post- baseline.
Outcome measures
| Measure |
BI 695501
n=321 Participants
Each patient received 40 milligram (mg)/0.8 millilitre (mL) BI 695501 solution for injection, administered by subcutaneous (SC) injection every 2 weeks up to and including the first 22 weeks of treatment (Period 1).
|
US-licensed Humira®
n=318 Participants
Each patient received 40 mg/0.8 mL US-licenced Humira® solution for injection, administered by SC injection every 2 weeks up to and including the first 22 weeks of treatment (Period 1).
|
|---|---|---|
|
The Proportion of Patients Meeting the American College of Rheumatology 20% (ACR20) Response Criteria at Week 12
|
67.0 Percentage of Patients
|
61.1 Percentage of Patients
|
PRIMARY outcome
Timeframe: Week 24Population: Full Analysis Set. Patients who discontinued treatment prior to the time-point had their binary response imputed as non-responder, a method commonly known as non-responder imputation. For truly missing data at the component level, multiple imputation was used.
ACR20 at Week 12 and Week 24 are standard outcome criteria that are widely accepted for regulatory purposes to demonstrate efficacy in treating the signs and symptoms of Rheumatoid arthritis (RA). The proportion of patients meeting the ACR20 response criteria was assessed at Week 12 and Week 24 to provide a robust comparison with US-licensed Humira® data. A patient had an ACR20 response if all of the following occurred: A ≥ 20 % improvement in the swollen joint count (66 joints), A ≥ 20 % improvement in the tender joint count (68 joints), A ≥ 20 % improvement in at least three of the following assessments: Patient's assessment of pain, Patient's global assessment of disease activity (equivalent to the General Health component of the Disease Activity Score (\[DAS\]), Physician's global assessment of disease activity, Patient's assessment of physical function, as measured by the Health Assessment Questionnaire - Disability Index (HAQ-DI) Acute phase reactant (C-reactive protein \[CRP\]).
Outcome measures
| Measure |
BI 695501
n=321 Participants
Each patient received 40 milligram (mg)/0.8 millilitre (mL) BI 695501 solution for injection, administered by subcutaneous (SC) injection every 2 weeks up to and including the first 22 weeks of treatment (Period 1).
|
US-licensed Humira®
n=318 Participants
Each patient received 40 mg/0.8 mL US-licenced Humira® solution for injection, administered by SC injection every 2 weeks up to and including the first 22 weeks of treatment (Period 1).
|
|---|---|---|
|
The Proportion of Patients Meeting ACR20 Response Criteria at Week 24
|
69.0 Percentage of Patients
|
64.5 Percentage of Patients
|
SECONDARY outcome
Timeframe: Baseline, Week 12 and Week 24Population: Full Analysis Set. Patients who discontinued treatment prior to the time-point had their binary response imputed as non-responder, a method commonly known as non-responder imputation. For truly missing data at the component level, multiple imputation was used.
The DAS28 (ESR) score was derived using the following formulae: DAS28 (ESR) = 0.56\*√(TJC28) + 0.28\*√(SJC28) + 0.014\*(GH) + 0.7\*ln(ESR) Where: * TJC28 = 28 joint count for tenderness * SJC28 = 28 joint count for swelling * Ln (ESR) = natural logarithm of ESR * GH = General Health component of the DAS (patient's global assessment of disease activity). DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. Actual number of patient analysed (N) is mean number of subjects in the analysis set with DAS28(ESR) results computable across the multiply imputed data sets. It is 319.6, 317.1 for week 12 and 313.9, 315.1 for week 24 for BI 695501 and US-licensed Humira® respectively.
Outcome measures
| Measure |
BI 695501
n=321 Participants
Each patient received 40 milligram (mg)/0.8 millilitre (mL) BI 695501 solution for injection, administered by subcutaneous (SC) injection every 2 weeks up to and including the first 22 weeks of treatment (Period 1).
|
US-licensed Humira®
n=318 Participants
Each patient received 40 mg/0.8 mL US-licenced Humira® solution for injection, administered by SC injection every 2 weeks up to and including the first 22 weeks of treatment (Period 1).
|
|---|---|---|
|
Change From Baseline in Disease Activity Score 28 (DAS28) (Erythrocyte Sedimentation Rate [ESR]) at Week 12 and Week 24
Week 12
|
-2.1 Units on a scale
Interval -2.28 to -2.01
|
-2.0 Units on a scale
Interval -2.18 to -1.91
|
|
Change From Baseline in Disease Activity Score 28 (DAS28) (Erythrocyte Sedimentation Rate [ESR]) at Week 12 and Week 24
Week 24
|
-2.4 Units on a scale
Interval -2.51 to -2.21
|
-2.4 Units on a scale
Interval -2.54 to -2.24
|
SECONDARY outcome
Timeframe: From the first drug administration until 10 weeks after the last drug administration, up to 58 weeksPopulation: The Safety Analysis Set contained all patients who received at least one dose of trial drug.
The analysis of AEs was based on the concept of treatment-emergent AEs (TEAEs). Thus, all AEs with an onset after the first dose of trial drug up to a period of ten weeks after the last dose of trial drug were assigned to the current treatment for evaluation. Investigator-assessed drug related AEs were AEs with a relationship to drug ticked "yes" according to the Investigator. Overall results are presented from Day 1 up to Week 58 and are based on the initial randomization groups. The comparison therefore focuses on patients who received BI 695501 continuously versus patients who received Humira® continuously for the long term assessment of safety. One patient was initially treated with Humira and discontinued prior to Week 24. This patient was mistakenly re randomized to BI 695501 but not treated. For safety this was counted in Humira not re-randomized group (as treated), and for other analysis sets, this patient was counted in the Humira to BI 695501 group (as randomized).
Outcome measures
| Measure |
BI 695501
n=324 Participants
Each patient received 40 milligram (mg)/0.8 millilitre (mL) BI 695501 solution for injection, administered by subcutaneous (SC) injection every 2 weeks up to and including the first 22 weeks of treatment (Period 1).
|
US-licensed Humira®
n=175 Participants
Each patient received 40 mg/0.8 mL US-licenced Humira® solution for injection, administered by SC injection every 2 weeks up to and including the first 22 weeks of treatment (Period 1).
|
|---|---|---|
|
The Percentage of Patients With Investigator-assessed Drug-related Adverse Events (AEs) During the Treatment Phase
|
19.1 Percentage of Patients
|
22.9 Percentage of Patients
|
Adverse Events
BI 695501 Continuously
Serious events: 18 serious events
Other events: 35 other events
Deaths: 0 deaths
US-licensed Humira® Continuously
Serious events: 17 serious events
Other events: 24 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
BI 695501 Continuously
n=324 participants at risk
BI 695501 continuously comprised all patients randomized to BI 695501 in Period 1 and re-randomized to BI 695501 in Period 2 (or not re randomized at Week 24). This group represents all patients who were to receive BI 695501 from Day 1 to Week 48. Each patient received 40 mg/0.8 mL BI 695501 solution for injection, administered by SC injection every 2 weeks.
|
US-licensed Humira® Continuously
n=174 participants at risk
Humira® US continuously comprised all patients randomized to US-licensed Humira® in Period 1 and re-randomized to US-licensed Humira® in Period 2 or not re randomized at Week 24 (e.g. patients who discontinued treatment prior to Week 24). This group represents all patients who were to receive US-licensed Humira® from Day 1 to Week 48. Each patient received 40 mg/0.8 mL US-licensed Humira® solution for injection, administered by SC injection every 2 weeks.
|
|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.57%
1/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Cardiac disorders
Hypertensive cardiomyopathy
|
0.00%
0/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.57%
1/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Cardiac disorders
Ventricular arrhythmia
|
0.00%
0/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.57%
1/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Eye disorders
Macular degeneration
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Gastrointestinal disorders
Chronic gastritis
|
0.00%
0/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.57%
1/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
General disorders
Chest pain
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Immune system disorders
Anaphylactic reaction
|
0.00%
0/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.57%
1/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Infections and infestations
Appendicitis
|
0.00%
0/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.57%
1/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Infections and infestations
Arthritis infective
|
0.00%
0/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.57%
1/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Infections and infestations
Bronchitis
|
0.00%
0/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.57%
1/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Infections and infestations
Cellulitis
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Infections and infestations
Otitis media
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Infections and infestations
Pneumonia
|
0.00%
0/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
1.7%
3/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
1.1%
2/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Injury, poisoning and procedural complications
Craniocerebral injury
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.57%
1/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.57%
1/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Injury, poisoning and procedural complications
Joint injury
|
0.00%
0/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.57%
1/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Investigations
Alanine aminotransferase increased
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Investigations
Aspartate aminotransferase increased
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Investigations
Hepatic enzyme increased
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Musculoskeletal and connective tissue disorders
Joint destruction
|
0.00%
0/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.57%
1/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.57%
1/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-Hodgkin's lymphoma
|
0.00%
0/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.57%
1/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostatic adenoma
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Nervous system disorders
Carotid artery stenosis
|
0.00%
0/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.57%
1/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Nervous system disorders
Cerebrovascular accident
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Nervous system disorders
Syncope
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Reproductive system and breast disorders
Endometrial hyperplasia
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.31%
1/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.00%
0/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Vascular disorders
Venous thrombosis limb
|
0.00%
0/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
0.57%
1/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
Other adverse events
| Measure |
BI 695501 Continuously
n=324 participants at risk
BI 695501 continuously comprised all patients randomized to BI 695501 in Period 1 and re-randomized to BI 695501 in Period 2 (or not re randomized at Week 24). This group represents all patients who were to receive BI 695501 from Day 1 to Week 48. Each patient received 40 mg/0.8 mL BI 695501 solution for injection, administered by SC injection every 2 weeks.
|
US-licensed Humira® Continuously
n=174 participants at risk
Humira® US continuously comprised all patients randomized to US-licensed Humira® in Period 1 and re-randomized to US-licensed Humira® in Period 2 or not re randomized at Week 24 (e.g. patients who discontinued treatment prior to Week 24). This group represents all patients who were to receive US-licensed Humira® from Day 1 to Week 48. Each patient received 40 mg/0.8 mL US-licensed Humira® solution for injection, administered by SC injection every 2 weeks.
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
5.9%
19/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
9.8%
17/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
|
Infections and infestations
Upper respiratory tract infection
|
5.2%
17/324 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
5.2%
9/174 • From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks
Treatment-emergent adverse events are defined as adverse events that started or worsened on or after the first dose of study medication and prior to the last date of study medication plus 10 weeks (70 days) inclusive. Data is reported from Day 1 to the end of Period 2 (Week 58).
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER