Study to Demonstrate Equivalent Efficacy and to Compare Safety of Biosimilar Etanercept (GP2015) and Enbrel (EGALITY)

• ClinicalTrials.gov Identifier: NCT01891864
• Recruitment Status: Completed
• First Posted: July 3, 2013
• Results First Posted: March 27, 2017
• Last Update Posted: March 27, 2017
• Sponsor: Sandoz
• Collaborator: Hexal AG
• Information provided by (Responsible Party): Sandoz

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Chronic Stable Plaque Psoriasis
• Interventions: Drug: GP2015 Etanercept; Drug: Enbrel
• Enrollment: 531

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	GP2015 Etanercept	Enbrel ® Etanercept	GP2015 Etanercept Continued	Enbrel ® Etanercept Continued	GP2015 Etanercept Switched	Enbrel ® Etanercept Switched
Arm/Group Description	Solution for subcutaneous injection in pre-filled syringe. The drug is administered in a dose of 50 mg twice weekly for the first 12 weeks and 50 mg once weekly thereafter GP2015 Etanercept	Solution for subcutaneous injection in pre-filled syringe. The drug is administered in a dose of 50 mg twice weekly for the first 12 weeks and 50 mg once weekly thereafter Enbrel ® Etanercept	GP2015 50 mg subcutaneous (s.c.) injection of study drug from week 13 until Week 30 (Treatment Period 2). GP2015 50 mg subcutaneous (s.c.) injection of study drug from week 31 until Week 52 (Extension Period) in patients who had completed Treatment Period 2	Enbrel ® 50 mg subcutaneous (s.c.) injection of study drug from week 13 until Week 30 (Treatment Period 2) Enbrel ® 50 mg subcutaneous (s.c.) injection of study drug from week 31 until Week 52 (Extension Period) in patients who had completed Treatment Period 2.	GP2015/Enbrel ® 50 mg subcutaneous (s.c.) injection of study drug until Week 30. Three periods of 6 weeks alternating between Enbrel/GP2015/Enbrel (Treatment Period 2). Enbrel ® 50 mg subcutaneous (s.c.) injection of study drug from week 31 until Week 52 (Extension Period) in patients who had completed Treatment Period 2.	Enbrel ®/GP2015 50 mg subcutaneous (s.c.) injection of study drug until Week 30. Three periods of 6 weeks alternating between GP2015/Enbrel/GP2015 (Treatment Period 2). GP2015 50 mg subcutaneous (s.c.) injection of study drug from week 31 until Week 52 (Extension Period) in patients who had completed Treatment Period 2.
Period Title: Treatment Period 1
Started	264	267	0 [1]	0 [1]	0 [1]	0 [1]
Completed	256 [2]	255 [3]	0	0	0	0
Not Completed	8	12	0	0	0	0
Reason Not Completed
Protocol Violation / IMP non-compliance	1	1	0	0	0	0
Physician Decision	0	1	0	0	0	0
Adverse Event, Serious, Fatal	0	1	0	0	0	0
Adverse Event / Injection Site Reaction	4	4	0	0	0	0
Withdrawal by Subject	2	5	0	0	0	0
Lost to Follow-up	1	0	0	0	0	0
[1] Treatment arm applicable only in Treatment Period 2 and Extension Period; [2] 6 patients discontinued after completion of Treatment Period 1 and did NOT start Treatment Period 2; [3] 8 patients discontinued after completion of Treatment Period 1 and did NOT start Treatment Period 2
Period Title: Treatment Period 2
Started	0 [1]	0 [1]	150 [2]	151 [3]	100 [2]	96 [3]
Completed	0	0	143	142	96	91
Not Completed	0	0	7	9	4	5
Reason Not Completed
Protocol Violation	0	0	0	1	0	0
Physician Decision	0	0	1	0	0	0
Site Termination	0	0	1	2	0	0
Lack of Efficacy	0	0	1	0	1	0
Adverse Event	0	0	1	2	0	4
Termination of Site	0	0	0	0	2	0
Withdrawal by Subject	0	0	3	4	1	1
[1] Treatment arm applicable for Treatment Period 1 only (patients re-randomized in Treatment Period 2); [2] Part of the patients re-randomized from "GP2015 Etanercept" treatment arm in Treatment Period 1; [3] Part of the patients re-randomized from "Enbrel ® Etanercept" treatment arm in Treatment Period 1
Period Title: Extension Period
Started	0	0	140 [1]	142	95 [2]	90 [3]
Completed	0	0	132	137	88	90
Not Completed	0	0	8	5	7	0
Reason Not Completed
Lack of Efficacy	0	0	0	1	1	0
Pregnancy	0	0	1	0	0	0
Adverse Event	0	0	4	2	2	0
Withdrawal by Subject	0	0	1	2	4	0
Lost to Follow-up	0	0	2	0	0	0
[1] 2 patients withdrew consent 1 patient lost to FU between Treatment Period 2 and the Extension period; [2] 1 patient discontinued between Treatment Period 2 and Extension Period due to lack of efficacy; [3] 1 patient discontinued between Treatment Period 2 and Extension Period due to an adverse event

Baseline Characteristics

Arm/Group Title		GP2015 Etanercept	Enbrel ® Etanercept	Total
Arm/Group Description		Solution for subcutaneous injection in pre-filled syringe. The drug is administered in a dose of 50 mg twice weekly for the first 12 weeks and 50 mg once weekly thereafter GP2015 Etanercept	Solution for subcutaneous injection in pre-filled syringe. The drug is administered in a dose of 50 mg twice weekly for the first 12 weeks and 50 mg once weekly thereafter Enbrel ® Etanercept	Total of all reporting groups
Overall Number of Baseline Participants		264	267	531
Baseline Analysis Population Description		All patients randomized in GP15-302 study
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	264 participants	267 participants	531 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	254 96.2%	249 93.3%	503 94.7%
	>=65 years	10 3.8%	18 6.7%	28 5.3%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	264 participants	267 participants	531 participants
		42.1 (12.29)	42.7 (12.86)	42.4 (12.57)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	264 participants	267 participants	531 participants
	Female	107 40.5%	95 35.6%	202 38.0%
	Male	157 59.5%	172 64.4%	329 62.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	264 participants	267 participants	531 participants
Czech Republic		25	16	41
Russian Federation		9	8	17
Romania		9	24	33
Hungary		9	12	21
Ukraine		19	23	42
Poland		96	94	190
South Africa		4	1	5
United Kingdom		10	4	14
Slovakia		17	20	37
Bulgaria		13	8	21
Germany		12	17	29
Estonia		41	40	81

Outcome Measures

1. Primary Outcome

Title	PASI 75 Response Rate at Week 12 - GP2015 Etanercept vs. Enbrel ® Etanercept
Description	The 95% CI for the Psoriasis Area and Severity Index (PASI) 75 response rate differences at Week12 between GP2015 Etanercept and Enbrel ® Etanercept. PASI 75 response: patients who achieved ≥ 75% improvement (reduction) in PASI score compared to baseline were defined as PASI 75 responders. PASI scores can range from 0, corresponding to no signs of psoriasis up to theoretic maximum of 72.0, which means a higher PASI score reflects a higher psoriasis activity.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The analysis of the primary outcome measure was based on the per-protocol set (PPS) consisting of patients who completed study until 12 weeks without any major protocol deviation.

Arm/Group Title	GP2015 Etanercept	Enbrel ® Etanercept
Arm/Group Description:	Solution for subcutaneous injection in pre-filled syringe. The drug is administered in a dose of 50 mg twice weekly for the first 12 weeks and 50 mg once weekly thereafter GP2015 Etanercept	Solution for subcutaneous injection in pre-filled syringe. The drug is administered in a dose of 50 mg twice weekly for the first 12 weeks and 50 mg once weekly thereafter Enbrel ® Etanercept
Overall Number of Participants Analyzed	239	241
Measure Type: Number; Unit of Measure: % of patients achieving PASI75 response
	73.4	75.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GP2015 Etanercept, Enbrel ® Etanercept
	Comments	PASI 75 response rate (proportion of patients showing at least a 75% improvement in PASI) after the first 12 weeks of treatment (Treatment Period 1) was the primary endpoint to assess equivalence between GP2015 and Enbrel®. Therapeutic equivalence in terms of PASI75 could be concluded if the exact 95% confidence interval for the difference in the PASI75 rates is completely contained within the interval [-18%; 18%]. A logistic regression model was to be employed.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The equivalence margin for the comparison of GP2015 with Enbrel with respect to PASI 75 response at Week 12 was based on response rates reported in two pivotal placebo controlled trials (Leonardi et al 2003; Papp et al 2005). Based on the observed effect size of 45-46%, an equivalence margin of 18% was chosen so that at least 60% of the treatment effect seen for Enbrel was maintained. A response rate of 49% was assumed for the comparator treatment Enbrel.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95%; -9.85 to 5.3
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Percent Change From Baseline in PASI Score up to Week 12
Description	The key secondary efficacy endpoint was the % change from baseline in PASI score up to Week 12. PASI scores can range from 0, corresponding to no signs of psoriasis up to theoretic maximum of 72.0, which means a higher PASI score reflects a higher psoriasis activity. Two approaches (longitudinal approach applying a Mixed Model Repeated Measures and Averaged Treatment Effect approach applying an ANCOVA model) were employed in order to calculate 2-sided 95% confidence intervals (CI) for the difference between the treatment groups.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The analysis was based on the per-protocol set (PPS) consisting of patients who completed study until 12 weeks without any major protocol deviation.

Arm/Group Title	GP2015 Etanercept	Enbrel ® Etanercept
Arm/Group Description:	Solution for subcutaneous injection in pre-filled syringe. The drug is administered in a dose of 50 mg twice weekly for the first 12 weeks and 50 mg once weekly thereafter GP2015 Etanercept	Solution for subcutaneous injection in pre-filled syringe. The drug is administered in a dose of 50 mg twice weekly for the first 12 weeks and 50 mg once weekly thereafter Enbrel ® Etanercept
Overall Number of Participants Analyzed	239	241
Least Squares Mean (Standard Error); Unit of Measure: percentage difference
	-56.11 (1.0578)	-55.48 (1.0511)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GP2015 Etanercept, Enbrel ® Etanercept
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A MMRM (Mixed Model Repeated Method) was performed on the percentage change from baseline in PASI score from baseline to Week 12. Therapeutic equivalence in terms of the % change from baseline in PASI score was to be determined if the 95% CI for the difference between GP2015 and Enbrel was contained within the interval [-15%; 15%].
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.64
	Confidence Interval	(2-Sided) 95%; -3.474 to 2.204
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GP2015 Etanercept, Enbrel ® Etanercept
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The mean averaged treatment effect (ATE) of percent change from baseline in PASI score up to week 12 was derived for each patient and analyzed using an ANCOVA approach. Therapeutic equivalence in terms of the % change from baseline in PASI score was to be determined if the 95% CI for the difference between GP2015 and Enbrel was contained within the interval [-15%; 15%].
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.88
	Confidence Interval	(2-Sided) 95%; -3.61 to 1.845
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	PASI 50, 75 and 90 Response Rates
Description	Percentage of patients achieving Psoriasis Area and Severity Index (PASI) 50, PASI 75, and PASI 90 responses at Week 12. PASI 50 response: patients who achieved ≥ 50% improvement (reduction) in PASI score compared to baseline were defined as PASI 50 responders .PASI 90 response: patients who achieved ≥ 90% improvement (reduction) in PASI score compared to baseline were defined as PASI 90 responders .
Time Frame	Week12

Outcome Measure Data

Analysis Population Description

The analysis of this secondary outcome measure was based on the per-protocol set (PPS) consisting of patients who completed study until 12 weeks without any major protocol deviation.

Arm/Group Title	GP2015 Etanercept	Enbrel ® Etanercept
Arm/Group Description:	Solution for subcutaneous injection in pre-filled syringe. The drug is administered in a dose of 50 mg twice weekly for the first 12 weeks and 50 mg once weekly thereafter GP2015 Etanercept	Solution for subcutaneous injection in pre-filled syringe. The drug is administered in a dose of 50 mg twice weekly for the first 12 weeks and 50 mg once weekly thereafter Enbrel ® Etanercept
Overall Number of Participants Analyzed	239	241
Measure Type: Number; Unit of Measure: percentage of patients
% of patients achieving PASI50 response at Week 12	99.2	97.9
% of patients achieving PASI75 response at Week 12	73.4	75.7
% of patients achieving PASI90 response at Week 12	39.2	34.1

4. Secondary Outcome

Title	Injection Site Reactions
Description	Percentage of patients with injection site reactions up to Week 52
Time Frame	Week52

Outcome Measure Data

Analysis Population Description

The analysis was performed on safety set including all patients who took at least 1 dose of study treatment

Arm/Group Title	GP2015 Etanercept Continued	Enbrel ® Etanercept Switched	GP2015 Etanercept Switched	Enbrel ® Etanercept Continued
Arm/Group Description:	GP2015 Etanercept (s.c.) injection administered in a dose of 50 mg twice weekly for the first 12 weeks. GP2015 Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug from week 13 until Week 30 (Treatment Period 2). GP2015 Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug from week 31 until Week 52 (Extension Period) in patients who had completed Treatment Period 2.	Enbrel ® Etanercept (s.c.) injection administered in a dose of 50 mg twice weekly for the first 12 weeks. Enbrel ® Etanercept /GP2015 Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug until Week 30. Three periods of 6 weeks alternating between GP2015/Enbrel/GP2015 (Treatment Period 2). GP2015 Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug from week 31 until Week 52 (Extension Period) in patients who had completed Treatment Period 2.	GP2015 Etanercept (s.c.) injection administered in a dose of 50 mg twice weekly for the first 12 weeks. GP2015 Etanercept /Enbrel ® Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug until Week 30. Three periods of 6 weeks alternating between Enbrel/GP2015/Enbrel (Treatment Period 2). Enbrel ® Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug from week 31 until Week 52 (Extension Period) in patients who had completed Treatment Period 2.	Enbrel ® Etanercept (s.c.) injection administered in a dose of 50 mg twice weekly for the first 12 weeks. Enbrel ® Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug from week 13 until Week 30 (Treatment Period 2). Enbrel ® Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug from week 31 until Week 52 (Extension Period) in patients who had completed Treatment Period 2.
Overall Number of Participants Analyzed	164	96	100	171
Measure Type: Number; Unit of Measure: percentage of patients with ISRs
	8.5	16.7	9.0	15.8

5. Secondary Outcome

Title	Immunogenicity: Measurement of Rate of ADA Formations Against GP2015 Etanercept and Enbrel ® Etanercept
Description	Immunogenicity was analyzed by the percentage of patients with positive anti-drug antibodies (ADA) to either GP2015 Etanercept or Enbrel ® up to Week 52.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The analysis was performed on immunogenicity set consisting of patients who provided data for ADA assessment of etanercept at baseline visit.

Arm/Group Title	GP2015 Etanercept Continued	Enbrel ® Etanercept Switched	GP2015 Etanercept Switched	Enbrel ® Etanercept Continued
Arm/Group Description:	GP2015 Etanercept (s.c.) injection administered in a dose of 50 mg twice weekly for the first 12 weeks. GP2015 Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug from week 13 until Week 30 (Treatment Period 2). GP2015 Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug from week 31 until Week 52 (Extension Period) in patients who had completed Treatment Period 2.	Enbrel ® Etanercept (s.c.) injection administered in a dose of 50 mg twice weekly for the first 12 weeks. Enbrel ® Etanercept /GP2015 Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug until Week 30. Three periods of 6 weeks alternating between GP2015/Enbrel/GP2015 (Treatment Period 2). GP2015 Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug from week 31 until Week 52 (Extension Period) in patients who had completed Treatment Period 2.	GP2015 Etanercept (s.c.) injection administered in a dose of 50 mg twice weekly for the first 12 weeks. GP2015 Etanercept /Enbrel ® Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug until Week 30. Three periods of 6 weeks alternating between Enbrel/GP2015/Enbrel (Treatment Period 2). Enbrel ® Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug from week 31 until Week 52 (Extension Period) in patients who had completed Treatment Period 2.	Enbrel ® Etanercept (s.c.) injection administered in a dose of 50 mg twice weekly for the first 12 weeks. Enbrel ® Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug from week 13 until Week 30 (Treatment Period 2). Enbrel ® Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug from week 31 until Week 52 (Extension Period) in patients who had completed Treatment Period 2.
Overall Number of Participants Analyzed	140	90	95	142
Measure Type: Number; Unit of Measure: percentage patients with positive ADA
	0	1.1	0	3.5

Adverse Events

Time Frame	Adverse events are reported until the end of the study (week 52).
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	GP2015 Etanercept Continued		Enbrel ® Etanercept Switched		GP2015 Etanercept Switched		Enbrel ® Etanercept Continued
Arm/Group Description	GP2015 Etanercept (s.c.) injection administered in a dose of 50 mg twice weekly for the first 12 weeks. GP2015 Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug from week 13 until Week 30 (Treatment Period 2). GP2015 Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug from week 31 until Week 52 (Extension Period) in patients who had completed Treatment Period 2.		Enbrel ® Etanercept (s.c.) injection administered in a dose of 50 mg twice weekly for the first 12 weeks. Enbrel ® Etanercept /GP2015 Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug until Week 30. Three periods of 6 weeks alternating between GP2015/Enbrel/GP2015 (Treatment Period 2). GP2015 Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug from week 31 until Week 52 (Extension Period) in patients who had completed Treatment Period 2.		GP2015 Etanercept (s.c.) injection administered in a dose of 50 mg twice weekly for the first 12 weeks. GP2015 Etanercept /Enbrel ® Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug until Week 30. Three periods of 6 weeks alternating between Enbrel/GP2015/Enbrel (Treatment Period 2). Enbrel ® Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug from week 31 until Week 52 (Extension Period) in patients who had completed Treatment Period 2.		Enbrel ® Etanercept (s.c.) injection administered in a dose of 50 mg twice weekly for the first 12 weeks. Enbrel ® Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug from week 13 until Week 30 (Treatment Period 2). Enbrel ® Etanercept 50 mg subcutaneous (s.c.) weekly injection of study drug from week 31 until Week 52 (Extension Period) in patients who had completed Treatment Period 2.
All-Cause Mortality
	GP2015 Etanercept Continued		Enbrel ® Etanercept Switched		GP2015 Etanercept Switched		Enbrel ® Etanercept Continued
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--
Serious Adverse Events
	GP2015 Etanercept Continued		Enbrel ® Etanercept Switched		GP2015 Etanercept Switched		Enbrel ® Etanercept Continued
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/164 (4.27%)		6/96 (6.25%)		6/100 (6.00%)		7/171 (4.09%)
Cardiac disorders
Cardiopulmonary failure † 1 [1]	0/164 (0.00%)	0	0/96 (0.00%)	0	0/100 (0.00%)	0	1/171 (0.58%)	1
Eye disorders
Retinal detachment † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	0/100 (0.00%)	0	0/171 (0.00%)	0
Gastrointestinal disorders
Umbilical hernia † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	1/100 (1.00%)	1	0/171 (0.00%)	0
Mesenteric vascular insufficiency † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	0/100 (0.00%)	0	1/171 (0.58%)	1
General disorders
Fatigue † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	1/100 (1.00%)	1	0/171 (0.00%)	0
Hepatobiliary disorders
Drug-induced liver injury † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	0/100 (0.00%)	0	1/171 (0.58%)	1
Cholelithiasis † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	1/100 (1.00%)	1	0/171 (0.00%)	0
Immune system disorders
Milk allergy † 1	1/164 (0.61%)	1	0/96 (0.00%)	0	0/100 (0.00%)	0	0/171 (0.00%)	0
Infections and infestations
Appendicitis † 1	1/164 (0.61%)	1	0/96 (0.00%)	0	0/100 (0.00%)	0	0/171 (0.00%)	0
Pneumonia † 1	1/164 (0.61%)	1	0/96 (0.00%)	0	0/100 (0.00%)	0	1/171 (0.58%)	1
Brain abscess † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	0/100 (0.00%)	0	1/171 (0.58%)	1
Lobar pneumonia † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	0/100 (0.00%)	0	1/171 (0.58%)	1
Sepsis † 1	1/164 (0.61%)	1	0/96 (0.00%)	0	0/100 (0.00%)	0	0/171 (0.00%)	0
Diverticulitis † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	0/100 (0.00%)	0	0/171 (0.00%)	0
Tonsillitis † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	0/100 (0.00%)	0	0/171 (0.00%)	0
Eczema infected † 1	1/164 (0.61%)	1	0/96 (0.00%)	0	0/100 (0.00%)	0	0/171 (0.00%)	0
Injury, poisoning and procedural complications
Meniscus injury † 1	1/164 (0.61%)	1	0/96 (0.00%)	0	0/100 (0.00%)	0	0/171 (0.00%)	0
Upper limb fracture † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	0/100 (0.00%)	0	1/171 (0.58%)	1
Lower limb fracture † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	1/100 (1.00%)	1	0/171 (0.00%)	0
Metabolism and nutrition disorders
Acid-base balance disorder mixed † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	1/100 (1.00%)	1	0/171 (0.00%)	0
Musculoskeletal and connective tissue disorders
Psoriatic arthropathy † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	1/100 (1.00%)	1	0/171 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma in situ † 1	1/164 (0.61%)	1	0/96 (0.00%)	0	0/100 (0.00%)	0	0/171 (0.00%)	0
Squamous cell carcinoma of the cervix † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	1/100 (1.00%)	1	0/171 (0.00%)	0
Nervous system disorders
Cerebral infarction † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	0/100 (0.00%)	0	0/171 (0.00%)	0
Multiple sclerosis † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	1/100 (1.00%)	1	0/171 (0.00%)	0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous † 1	1/164 (0.61%)	1	0/96 (0.00%)	0	0/100 (0.00%)	0	0/171 (0.00%)	0
Renal and urinary disorders
Renal failure acute † 1	1/164 (0.61%)	1	0/96 (0.00%)	0	1/100 (1.00%)	1	0/171 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory failure † 1	1/164 (0.61%)	1	0/96 (0.00%)	0	1/100 (1.00%)	1	0/171 (0.00%)	0
Epistaxis † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	0/100 (0.00%)	0	1/171 (0.58%)	1
Pulmonary sarcoidosis † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	0/100 (0.00%)	0	0/171 (0.00%)	0
Chronic obstructive pulmonary disease † 1	1/164 (0.61%)	1	0/96 (0.00%)	0	0/100 (0.00%)	0	0/171 (0.00%)	0
Skin and subcutaneous tissue disorders
Psoriasis † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	1/100 (1.00%)	1	0/171 (0.00%)	0
Vascular disorders
Thrombophlebitis † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	0/100 (0.00%)	0	0/171 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (17.0); [1] Fatal event
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	1%
	GP2015 Etanercept Continued		Enbrel ® Etanercept Switched		GP2015 Etanercept Switched		Enbrel ® Etanercept Continued
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	97/164 (59.15%)		57/96 (59.38%)		60/100 (60.00%)		94/171 (54.97%)
Blood and lymphatic system disorders
Lymphadenopathy † 1	4/164 (2.44%)	4	1/96 (1.04%)	1	1/100 (1.00%)	1	0/171 (0.00%)	0
Lymph node pain † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	1/100 (1.00%)	1	0/171 (0.00%)	0
Eye disorders
Eye haemorrhage † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	1/100 (1.00%)	1	0/171 (0.00%)	0
Gastrointestinal disorders
Diarrhoea † 1	4/164 (2.44%)	4	3/96 (3.13%)	3	1/100 (1.00%)	1	2/171 (1.17%)	2
Abdominal pain upper † 1	3/164 (1.83%)	3	0/96 (0.00%)	0	0/100 (0.00%)	0	3/171 (1.75%)	3
Nausea † 1	0/164 (0.00%)	0	2/96 (2.08%)	2	1/100 (1.00%)	1	0/171 (0.00%)	0
Toothache † 1	0/164 (0.00%)	0	3/96 (3.13%)	3	0/100 (0.00%)	0	0/171 (0.00%)	0
Gastritis † 1	0/164 (0.00%)	0	2/96 (2.08%)	2	2/100 (2.00%)	2	4/171 (2.34%)	4
Dental caries † 1	0/164 (0.00%)	0	2/96 (2.08%)	3	0/100 (0.00%)	0	0/171 (0.00%)	0
General disorders
Pyrexia † 1	0/164 (0.00%)	0	2/96 (2.08%)	2	2/100 (2.00%)	2	0/171 (0.00%)	0
Fatigue † 1	1/164 (0.61%)	1	0/96 (0.00%)	0	0/100 (0.00%)	0	3/171 (1.75%)	3
Hepatobiliary disorders
Hepatitis alcoholic † 1	0/164 (0.00%)	0	2/96 (2.08%)	2	0/100 (0.00%)	0	0/171 (0.00%)	0
Hepatic steatosis † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	1/100 (1.00%)	1	0/171 (0.00%)	0
Infections and infestations
Nasopharyngitis † 1	20/164 (12.20%)	26	10/96 (10.42%)	15	14/100 (14.00%)	16	17/171 (9.94%)	22
Pharyngitis † 1	7/164 (4.27%)	9	3/96 (3.13%)	4	5/100 (5.00%)	5	10/171 (5.85%)	11
Viral upper respiratory tract infection † 1	5/164 (3.05%)	6	8/96 (8.33%)	12	4/100 (4.00%)	6	6/171 (3.51%)	7
Respiratory tract infection viral † 1	4/164 (2.44%)	6	1/96 (1.04%)	1	4/100 (4.00%)	4	2/171 (1.17%)	4
Upper respiratory tract infection † 1	4/164 (2.44%)	4	3/96 (3.13%)	3	1/100 (1.00%)	2	5/171 (2.92%)	9
Bronchitis † 1	4/164 (2.44%)	4	0/96 (0.00%)	0	0/100 (0.00%)	0	3/171 (1.75%)	4
Rhinitis † 1	2/164 (1.22%)	2	3/96 (3.13%)	4	1/100 (1.00%)	1	4/171 (2.34%)	5
Tonsillitis † 1	5/164 (3.05%)	6	1/96 (1.04%)	1	1/100 (1.00%)	1	1/171 (0.58%)	1
Influenza † 1	2/164 (1.22%)	2	0/96 (0.00%)	0	0/100 (0.00%)	0	3/171 (1.75%)	3
Oral herpes † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	2/100 (2.00%)	3	0/171 (0.00%)	0
Viral infection † 1	3/164 (1.83%)	3	1/96 (1.04%)	1	1/100 (1.00%)	1	2/171 (1.17%)	2
Urinary tract infection † 1	2/164 (1.22%)	2	1/96 (1.04%)	1	2/100 (2.00%)	2	3/171 (1.75%)	3
Cystitis † 1	3/164 (1.83%)	3	0/96 (0.00%)	0	0/100 (0.00%)	0	1/171 (0.58%)	1
Conjunctivitis † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	1/100 (1.00%)	1	0/171 (0.00%)	0
Folliculitis † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	2/100 (2.00%)	2	0/171 (0.00%)	0
Herpes simplex † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	2/100 (2.00%)	2	0/171 (0.00%)	0
Sinusitis † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	1/100 (1.00%)	2	0/171 (0.00%)	0
Upper respiratory tract infection bacterial † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	1/100 (1.00%)	1	0/171 (0.00%)	0
Pyelonephritis † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	2/100 (2.00%)	2	0/171 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	6/164 (3.66%)	6	2/96 (2.08%)	2	1/100 (1.00%)	1	2/171 (1.17%)	2
Blood pressure increased † 1	2/164 (1.22%)	2	0/96 (0.00%)	0	4/100 (4.00%)	4	2/171 (1.17%)	2
Gamma-glutamyltransferase increased † 1	6/164 (3.66%)	6	0/96 (0.00%)	0	3/100 (3.00%)	3	0/171 (0.00%)	0
Weight increased † 1	2/164 (1.22%)	2	0/96 (0.00%)	0	3/100 (3.00%)	3	4/171 (2.34%)	4
Aspartate aminotransferase increased † 1	5/164 (3.05%)	5	2/96 (2.08%)	2	1/100 (1.00%)	1	1/171 (0.58%)	1
Blood uric acid increased † 1	3/164 (1.83%)	3	0/96 (0.00%)	0	0/100 (0.00%)	0	2/171 (1.17%)	2
Metabolism and nutrition disorders
Diabetes mellitus † 1	0/164 (0.00%)	0	2/96 (2.08%)	2	1/100 (1.00%)	1	0/171 (0.00%)	0
Hyperuricaemia † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	2/100 (2.00%)	2	0/171 (0.00%)	0
Musculoskeletal and connective tissue disorders
Spinal pain † 1	2/164 (1.22%)	2	0/96 (0.00%)	0	0/100 (0.00%)	0	2/171 (1.17%)	2
Back pain † 1	7/164 (4.27%)	8	4/96 (4.17%)	5	2/100 (2.00%)	2	3/171 (1.75%)	3
Arthralgia † 1	5/164 (3.05%)	6	5/96 (5.21%)	9	3/100 (3.00%)	4	7/171 (4.09%)	8
Pain in extremity † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	2/100 (2.00%)	2	0/171 (0.00%)	0
Myalgia † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	1/100 (1.00%)	1	0/171 (0.00%)	0
Musculoskeletal pain † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	1/100 (1.00%)	1	0/171 (0.00%)	0
Osteoarthritis † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	1/100 (1.00%)	1	0/171 (0.00%)	0
Nervous system disorders
Headache † 1	3/164 (1.83%)	3	3/96 (3.13%)	7	4/100 (4.00%)	5	8/171 (4.68%)	8
Somnolence † 1	0/164 (0.00%)	0	0/96 (0.00%)	0	2/100 (2.00%)	2	0/171 (0.00%)	0
Schiatica † 1	0/164 (0.00%)	0	2/96 (2.08%)	2	0/100 (0.00%)	0	0/171 (0.00%)	0
Renal and urinary disorders
Haematuria † 1	3/164 (1.83%)	3	1/96 (1.04%)	1	1/100 (1.00%)	1	1/171 (0.58%)	1
Respiratory, thoracic and mediastinal disorders
Cough † 1	3/164 (1.83%)	3	0/96 (0.00%)	0	3/100 (3.00%)	3	2/171 (1.17%)	2
Oropharyngeal pain † 1	3/164 (1.83%)	3	1/96 (1.04%)	1	3/100 (3.00%)	3	2/171 (1.17%)	3
Skin and subcutaneous tissue disorders
Psoriasis † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	2/100 (2.00%)	3	5/171 (2.92%)	5
Pruritus † 1	2/164 (1.22%)	2	0/96 (0.00%)	0	0/100 (0.00%)	0	4/171 (2.34%)	4
Dermatitis psoriasiform † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	1/100 (1.00%)	1	0/171 (0.00%)	0
Dermatitis allergic † 1	3/164 (1.83%)	3	0/96 (0.00%)	0	0/100 (0.00%)	0	1/171 (0.58%)	2
Pruritus generalized † 1	0/164 (0.00%)	0	1/96 (1.04%)	1	1/100 (1.00%)	1	0/171 (0.00%)	0
Vascular disorders
Hypertenson † 1	5/164 (3.05%)	5	2/96 (2.08%)	2	3/100 (3.00%)	3	7/171 (4.09%)	8
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (17.0)

Limitations and Caveats

None reported

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

At least sixty days prior to submitting/presenting manuscript or other materials relating to the study a copy should be provided to Sandoz and Sandoz has sixty days to review and comment. Sandoz has the right to require amendments to any such proposed presentation or publication on reasonable grounds. Sandoz may require any proposed publication or presentation to be delayed for up to four months to enable a patent application to be prepared and filed.

Results Point of Contact

• Name/Title: Dr Guido Wuerth - Global Program Medical Director
• Organization: Sandoz
• Phone: +4980244762925
• EMail: guido.wuerth@sandoz.com

• Responsible Party: Sandoz
• ClinicalTrials.gov Identifier: NCT01891864
• Other Study ID Numbers: GP15-302
• First Submitted: June 24, 2013
• First Posted: July 3, 2013
• Results First Submitted: September 26, 2016
• Results First Posted: March 27, 2017
• Last Update Posted: March 27, 2017