Trial Outcomes & Findings for A Study Of PF-05280586 (Rituximab-Pfizer) Or MabThera® (Rituximab-EU) For The First-Line Treatment Of Patients With CD20-Positive, Low Tumor Burden, Follicular Lymphoma (REFLECTIONS B328-06) (NCT NCT02213263)

Last Updated: 2019-06-20

Results Overview

ORR was defined as the percentage of participants who achieved complete response (CR) or partial response (PR) in accordance with the revised response criteria for malignant lymphoma (Cheson 2007). CR was defined as disappearance of all evidence of disease. PR was defined as regression of measureable disease and no new sites.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

394 participants

Primary outcome timeframe

Week 26

Results posted on

2019-06-20

Participant Flow

A total of 394 participants were enrolled and randomized in 1:1 ratio to 1 of the 2 study treatment arms: PF-05280586 (Rituximab-Pfizer) and Rituximab-EU (MabThera®).

Participant milestones

Participant milestones
Measure	Rituximab-EU Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Overall Study STARTED	198	196
Overall Study Treated	197	196
Overall Study COMPLETED	170	170
Overall Study NOT COMPLETED	28	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Rituximab-EU Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Overall Study Insufficient clinical response	4	3
Overall Study Lost to Follow-up	0	1
Overall Study No longer willing to participate	3	4
Overall Study Progressive disease	20	14
Overall Study Protocol Violation	0	1
Overall Study Adverse Event	1	3

Baseline Characteristics

A Study Of PF-05280586 (Rituximab-Pfizer) Or MabThera® (Rituximab-EU) For The First-Line Treatment Of Patients With CD20-Positive, Low Tumor Burden, Follicular Lymphoma (REFLECTIONS B328-06)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab-EU n=198 Participants Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 n=196 Participants Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	Total n=394 Participants Total of all reporting groups
Age, Continuous	58.3 years STANDARD_DEVIATION 12.8 • n=5 Participants	58.7 years STANDARD_DEVIATION 12.1 • n=7 Participants	58.5 years STANDARD_DEVIATION 12.4 • n=5 Participants
Sex: Female, Male Female	106 Participants n=5 Participants	110 Participants n=7 Participants	216 Participants n=5 Participants
Sex: Female, Male Male	92 Participants n=5 Participants	86 Participants n=7 Participants	178 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	26 Participants n=5 Participants	31 Participants n=7 Participants	57 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	172 Participants n=5 Participants	165 Participants n=7 Participants	337 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	44 Participants n=5 Participants	30 Participants n=7 Participants	74 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	146 Participants n=5 Participants	158 Participants n=7 Participants	304 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 26

Population: ITT population included all participants who were randomized.

Outcome measures

Outcome measures
Measure	Rituximab-EU n=198 Participants Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 n=196 Participants Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Overall Response Rate (ORR): Percentage of Participants With Overall Response (OR) at Week 26	70.7 percentage of participants Interval 63.8 to 76.9	75.5 percentage of participants Interval 68.9 to 81.4

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Safety population included all participants who received at least 1 dose of any study drug.

An AE was any untoward medical occurrence in participants who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious.

Outcome measures

Outcome measures
Measure	Rituximab-EU n=197 Participants Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 n=196 Participants Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	145 Participants	156 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	15 Participants	17 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Safety population included all participants who received at least 1 dose of any study drug.

Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state. Relatedness to treatment was assessed by investigator. AEs included both serious and non-serious AEs.

Outcome measures

Outcome measures
Measure	Rituximab-EU n=197 Participants Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 n=196 Participants Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Number of Participants With Treatment Related Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	94 Participants	86 Participants
Number of Participants With Treatment Related Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Safety population included all participants who received at least 1 dose of any study drug.

An AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Grade 1=Mild, asymptomatic or mild symptoms, Grade 2=Moderate; minimal, local or noninvasive intervention indicated, Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life threatening) events caused participant to be in imminent danger of death. Grade 5 = death. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state.

Outcome measures

Outcome measures
Measure	Rituximab-EU n=197 Participants Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 n=196 Participants Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Number of Participants With Grade 3 or Higher Treatment-Emergent Adverse Events (AEs) as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03	26 Participants	28 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Safety population included all participants who received at least 1 dose of any study drug.

Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Grade 1=Mild, asymptomatic or mild symptoms, Grade 2=Moderate; minimal, local or noninvasive intervention indicated; Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 = death. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state.

Outcome measures

Outcome measures
Measure	Rituximab-EU n=197 Participants Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 n=196 Participants Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Number of Participants With Grade 3 or Higher Treatment-Related Treatment-Emergent Adverse Events (AEs) as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03	8 Participants	9 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Safety population included all participants who received at least 1 dose of any study drug. Here, 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.

Criteria for clinically significant laboratory abnormalities included total bilirubin (TB) less than (\<) 2\*upper limit of normal (ULN), alanine aminotransferase (ALT)\<3\*ULN; TB\<2\*ULN, ALT more than (\>) 3 equal to (=) \*ULN; TB\<2\*ULN, aspartate aminotransferase (AST)\<3\*ULN; TB\<2\*ULN, AST\>=3\*ULN. Data for only those categories are reported for which at least one participant had clinically significant laboratory abnormality.

Outcome measures

Outcome measures
Measure	Rituximab-EU n=197 Participants Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 n=195 Participants Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Number of Participants With Clinically Significant Laboratory Abnormalities TB<2ULN, ALT<3ULN	194 Participants	192 Participants
Number of Participants With Clinically Significant Laboratory Abnormalities TB<2ULN, ALT>=3ULN	3 Participants	3 Participants
Number of Participants With Clinically Significant Laboratory Abnormalities TB<2ULN, AST<3ULN	196 Participants	195 Participants
Number of Participants With Clinically Significant Laboratory Abnormalities TB<2ULN, AST>=3ULN	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From randomization until disease progression, death or permanent discontinuation from treatment/study due to any reason, or up to Week 52

Population: ITT population included all participants who were randomized. Here. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.

TTF was defined as the time (in months) from date of randomization to first progression of disease based on central review, death due to any cause, or permanent discontinuation from treatment, or discontinuation from study for any reason, whichever came first. Progression was defined as any new lesion or increase by greater than or equal to (\>=) 50% of previously involved sites from nadir. TTF was calculated using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Rituximab-EU n=48 Participants Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 n=54 Participants Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Time to Treatment Failure (TTF)	18.9 months Interval 12.6 to 18.9	NA months Interval 12.3 to Due to smaller number of participants with an event, median and upper limit of 95% CI could not be calculated.

SECONDARY outcome

Timeframe: From randomization until disease progression or death due to any cause or up to Week 52

Population: ITT population included all participants who were randomized. Here. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.

PFS was defined as the time (in months) from date of randomization to first progression of disease (PD) based on central review or death due to any cause in the absence of documented PD. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir. PFS was calculated using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Rituximab-EU n=28 Participants Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 n=37 Participants Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Progression-Free Survival (PFS)	18.9 months Interval 12.6 to 18.9	NA months Due to smaller number of participants with an event, median and upper limit of 95% CI could not be calculated.

SECONDARY outcome

Timeframe: Week 26

Population: ITT population included all participants who were randomized.

Complete Remission (CR) was defined as disappearance of all evidence of disease. CR was assessed by central review based on scans done at Week 26.

Outcome measures

Outcome measures
Measure	Rituximab-EU n=198 Participants Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 n=196 Participants Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Percentage of Participants With Complete Remission (CR) at Week 26	28.3 percentage of participants Interval 22.1 to 35.1	26.0 percentage of participants Interval 20.0 to 32.8

SECONDARY outcome

Timeframe: From date of first documentation of overall response to first documentation of PD or to death due to any cause in absence of PD or up to Week 52

Population: The response-evaluable population was defined as all randomized participants who received at least 1 dose of study drug, had adequate disease assessment at baseline, and at least 1 post baseline response assessment. Here. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.

DOR was defined as the time (in months) from date of the first documentation of overall response (CR or PR) to the first documentation of progressive disease (PD) based on central review or to death due to any cause in the absence of documented PD. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measureable disease and no new sites. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir. DOR was calculated using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Rituximab-EU n=19 Participants Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 n=28 Participants Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Duration of Response (DOR)	15.4 months Interval 10.4 to 15.4	NA months Interval 9.6 to Due to smaller number of participants with an event, median and upper limit of 95% CI could not be calculated.

SECONDARY outcome

Timeframe: From randomization until death due to any cause or up to Week 52

Population: ITT population included all participants who were randomized.

Overall survival was defined as the time (in months) from date of randomization to death due to any cause. For participants who were alive, overall survival was censored at the last contact. Overall survival was calculated using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Rituximab-EU n=198 Participants Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 n=196 Participants Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Overall Survival	18.9 months Due to single participant with an event, lower and upper limit of 95% CI could not be calculated.	NA months Due to single participant with an event, median, lower and upper limit of 95% CI could not be calculated.

SECONDARY outcome

Timeframe: Predose (within 4 hours prior to start of infusion) on Days 1, 8, 15 and 22; within 15 minutes prior to end of infusion on Days 1 and 22

Population: The pharmacokinetic analysis set (PKAS) included participants who received at least 1 dose of any study drug and who provided at least one post-dose pharmacokinetic concentration. Here, 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Rituximab-EU n=132 Participants Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 n=138 Participants Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Maximum Observed Serum Concentration (Cmax) of PF-05280586 and Rituximab-EU	334848.88 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 33	337708.05 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 36

SECONDARY outcome

Timeframe: Predose (within 4 hours prior to the start of dosing) on Day 1, 8, 15, and 22

Population: The pharmacokinetic analysis set (PKAS) included participants who received at least 1 dose of any study drug and who provided at least one post-dose pharmacokinetic concentration. Here 'Number analyzed' signifies number of participants evaluable for this outcome measure at specified time points.

Outcome measures

Outcome measures
Measure	Rituximab-EU n=197 Participants Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 n=196 Participants Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Minimum Observed (Trough) Serum Concentration (Ctrough) of PF-05280586 and Rituximab-EU Day 1	0.01 ng/mL Geometric Coefficient of Variation 577	0.01 ng/mL Geometric Coefficient of Variation 1320
Minimum Observed (Trough) Serum Concentration (Ctrough) of PF-05280586 and Rituximab-EU Day 8	62311.74 ng/mL Geometric Coefficient of Variation 47	66669.15 ng/mL Geometric Coefficient of Variation 45
Minimum Observed (Trough) Serum Concentration (Ctrough) of PF-05280586 and Rituximab-EU Day 15	109619.73 ng/mL Geometric Coefficient of Variation 43	119026.91 ng/mL Geometric Coefficient of Variation 29
Minimum Observed (Trough) Serum Concentration (Ctrough) of PF-05280586 and Rituximab-EU Day 22	144650.79 ng/mL Geometric Coefficient of Variation 68	158294.91 ng/mL Geometric Coefficient of Variation 32

SECONDARY outcome

Timeframe: Baseline, Week 2, 3, 4, 5, 13, 26, 39, 52

Population: The modified ITT (mITT) Population included all participants who were randomized and received at least 1 dose of any study drug. Here 'Number analyzed' signifies number of participants evaluable for this outcome measure at specified time points.

Outcome measures

Outcome measures
Measure	Rituximab-EU n=197 Participants Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 n=196 Participants Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Cluster of Differentiation (CD) 19-Positive B-Cell Counts Baseline	114.2 Cells per microliter Interval 0.6 to 2313.1	119.9 Cells per microliter Interval 10.9 to 1310.1
Cluster of Differentiation (CD) 19-Positive B-Cell Counts Week 2	1.0 Cells per microliter Interval 0.2 to 44.8	0.8 Cells per microliter Interval 0.2 to 136.0
Cluster of Differentiation (CD) 19-Positive B-Cell Counts Week 3	0.6 Cells per microliter Interval 0.2 to 19.5	0.6 Cells per microliter Interval 0.2 to 248.1
Cluster of Differentiation (CD) 19-Positive B-Cell Counts Week 4	0.5 Cells per microliter Interval 0.2 to 8.7	0.4 Cells per microliter Interval 0.2 to 144.5
Cluster of Differentiation (CD) 19-Positive B-Cell Counts Week 5	0.5 Cells per microliter Interval 0.2 to 19.0	0.4 Cells per microliter Interval 0.2 to 19.0
Cluster of Differentiation (CD) 19-Positive B-Cell Counts Week 13	0.5 Cells per microliter Interval 0.2 to 130.7	0.5 Cells per microliter Interval 0.2 to 183.7
Cluster of Differentiation (CD) 19-Positive B-Cell Counts Week 26	1.2 Cells per microliter Interval 0.2 to 496.5	0.9 Cells per microliter Interval 0.2 to 329.8
Cluster of Differentiation (CD) 19-Positive B-Cell Counts Week 39	21.7 Cells per microliter Interval 0.3 to 341.0	10.7 Cells per microliter Interval 0.2 to 442.7
Cluster of Differentiation (CD) 19-Positive B-Cell Counts Week 52	60.8 Cells per microliter Interval 1.4 to 413.0	51.6 Cells per microliter Interval 0.3 to 597.9

SECONDARY outcome

Timeframe: Baseline up to Week 52

Human serum ADA samples were analyzed for the presence or absence of anti-rituximab antibodies or anti-PF-05280586 antibodies using the validated drug-specific assay with a tiered approach using screening, confirmation and titer/quantitation. Human NAb serum samples testing ADA positive were analyzed for the presence or absence of neutralizing anti-rituximab antibody and neutralizing anti-PF-05280586 antibody using the validated drug-specific assay with a tiered approach using screening, confirmation and titer/quantitation. Participants with their ADA titer \>= 1.88 were considered to be ADA positive. Only participants with a positive ADA result were further tested for NAb.

Outcome measures

Outcome measures
Measure	Rituximab-EU n=197 Participants Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 n=195 Participants Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) ADA Positive	39 Participants	43 Participants
Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) NAB Positive	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: The Safety analysis population include all participants who received at least 1 dose of any study treatment.

Immune-based adverse effects included infusion related reaction (IRR), adverse events which fulfill Sampson's criteria, and adverse events which belong to the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) anaphylaxis or hypersensitivity reactions. Potential allergic and anaphylactic reactions were identified programmatically based on the criteria of Sampson et al, (2006).

Outcome measures

Outcome measures
Measure	Rituximab-EU n=197 Participants Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 n=196 Participants Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Number of Participants Reporting Immune-Based Adverse Effects IRR reported	59 Participants	49 Participants
Number of Participants Reporting Immune-Based Adverse Effects AE based on Sampson's criteria	17 Participants	17 Participants
Number of Participants Reporting Immune-Based Adverse Effects Anaphylaxis/Hypersensitivity (SMQ)	48 Participants	39 Participants

Adverse Events

Rituximab-EU

Serious events: 15 serious events

Other events: 143 other events

Deaths: 1 deaths

PF-05280586

Serious events: 17 serious events

Other events: 153 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Rituximab-EU n=197 participants at risk Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 n=196 participants at risk Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Cardiac disorders Angina unstable	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Cardiac disorders Atrial fibrillation	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Cardiac disorders Intracardiac thrombus	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Gastrointestinal disorders Abdominal pain	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Gastrointestinal disorders Mesenteric artery stenosis	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
General disorders Disease progression	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
General disorders Non-cardiac chest pain	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
General disorders Pyrexia	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Immune system disorders Serum sickness	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Infections and infestations Appendicitis	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Infections and infestations Clostridium difficile infection	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Infections and infestations Diverticulitis	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Infections and infestations Escherichia sepsis	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Infections and infestations Hepatitis B	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Infections and infestations Kidney infection	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Infections and infestations Peritonitis	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Infections and infestations Urinary tract infection	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Infections and infestations Viral sinusitis	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Injury, poisoning and procedural complications Contusion	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Injury, poisoning and procedural complications Infusion related reaction	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Polyarthritis	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma stage I	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of lung	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Nervous system disorders Paraesthesia	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Nervous system disorders Transient ischaemic attack	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Gastrointestinal disorders Ileus	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Gastrointestinal disorders Inguinal hernia	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Hepatobiliary disorders Cholelithiasis	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.

Other adverse events
Measure	Rituximab-EU n=197 participants at risk Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m\^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.	PF-05280586 n=196 participants at risk Participants received PF-05280586 IV infusion at a dose of 375 mg/m\^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Infections and infestations Herpes zoster	1.5% 3/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Blood and lymphatic system disorders Anaemia	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Blood and lymphatic system disorders Lymph node pain	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Blood and lymphatic system disorders Lymphopenia	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Blood and lymphatic system disorders Neutropenia	1.5% 3/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Blood and lymphatic system disorders Thrombocytopenia	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Cardiac disorders Angina pectoris	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Cardiac disorders Angina unstable	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Cardiac disorders Atrial fibrillation	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	1.0% 2/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Cardiac disorders Bradycardia	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Cardiac disorders Cardiac failure congestive	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Cardiac disorders Palpitations	1.0% 2/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	2.6% 5/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Cardiac disorders Sinus bradycardia	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Cardiac disorders Tachycardia	1.0% 2/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Ear and labyrinth disorders Ear discomfort	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	1.0% 2/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Ear and labyrinth disorders Ear disorder	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Ear and labyrinth disorders Ear pain	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Ear and labyrinth disorders Ear pruritus	1.0% 2/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	1.5% 3/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Ear and labyrinth disorders Hypoacusis	1.0% 2/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	1.0% 2/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Ear and labyrinth disorders Tinnitus	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Ear and labyrinth disorders Vertigo	1.5% 3/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	1.0% 2/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Ear and labyrinth disorders Vertigo positional	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Endocrine disorders Hyperthyroidism	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Endocrine disorders Hypothyroidism	1.0% 2/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Endocrine disorders Thyroid cyst	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Eye disorders Accommodation disorder	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Eye disorders Cataract	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	1.0% 2/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Eye disorders Conjunctival disorder	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Eye disorders Diplopia	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Eye disorders Dry eye	1.0% 2/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Eye disorders Erythema of eyelid	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Eye disorders Eye pruritus	1.5% 3/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Eye disorders Lacrimation increased	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Eye disorders Meibomianitis	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Eye disorders Ocular hyperaemia	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.00% 0/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Gastrointestinal disorders Abdominal discomfort	0.51% 1/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Gastrointestinal disorders Abdominal pain	1.5% 3/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	3.6% 7/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	0.51% 1/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Gastrointestinal disorders Abdominal pain upper	2.5% 5/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	4.6% 9/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
General disorders Asthenia	6.6% 13/197 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.	4.6% 9/196 • Baseline up to end of study (up to 52 weeks) Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.