Study to Demonstrate Equivalent Efficacy and to Compare Safety of Biosimilar Adalimumab (GP2017) and Humira (ADACCESS)

• 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	Plaque Type Psoriasis
Interventions	Drug: GP2017 Adalimumab; Drug: Humira ® Adalimumab
Enrollment	465

Participant Flow

Recruitment Details	661 patients were screened. 465 patients were randomized 1:1 into Treatment Period 1 and stratified by region (US/EU), body weight (<90/≥90 kg) and prior systemic therapy (no/any). In Treatment Period 2 patients were re-randomized 2:1 to either continue originally assigned treatment or switch treatment and were stratified by region only.
Pre-assignment Details	Screening lasted for at least 2 weeks and up to 4 weeks. Main inclusion criteria: Men or women of at least 18 years; Chronic plaque-type psoriasis ≥ 6 months before randomization; Moderate to severe psoriasis : PASI score ≥ 12 IGA score ≥3 BSA affected by plaque-type psoriasis ≥ 10%; No previous exposure to adalimumab

Arm/Group Title	GP2017 Adalimumab	Humira ® Adalimumab	Humira ® Adalimumab Switched	Humira ® Adalimumab Continued	GP2017 Adalimumab Switched	GP2017 Adalimumab Continued
Arm/Group Description	Solution for subcutaneous (s.c.) injection in pre-filled syringe. Study drug is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1).	Solution for subcutaneous (s.c.) injection in pre-filled syringe. Study drug is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1).	Alternating treatment between GP2017/Humira ®/GP2017 subcutaneous (s.c.) injection of 40mg study drug (Treatment Period 2 / Week 17 until Week 35) followed by Humira ® subcutaneous (s.c.) injection of 40mg study drug (Extension Period / Week 35 until Week 51).	Humira ® subcutaneous (s.c.) injection of 40mg study drug from Week 17 until Week 35 (Treatment Period 2) and from Week 35 until Week 51 (Extension Period).	Alternating treatment between Humira ®/GP2017/Humira ® subcutaneous (s.c.) injection of 40mg study drug (Treatment Period 2 / Week 17 until Week 35) followed by GP2017 40mg subcutaneous (s.c.) injection of 40mg study drug (Extension Period / Week 35 until Week 51).	GP2017 subcutaneous (s.c.) injection of 40mg study drug from Week 17 until Week 35 (Treatment Period 2) and from Week 35 until Week 51 (Extension Period).
Period Title: TREATMENT PERIOD 1
Started	231	234	0 [1]	0 [1]	0 [1]	0 [1]
Completed	201 [2]	201 [3]	0	0	0	0
Not Completed	30	33	0	0	0	0
Reason Not Completed
Protocol Violation	2	8	0	0	0	0
Physician Decision	0	2	0	0	0	0
Lack of Efficacy	4	2	0	0	0	0
Pregnancy	0	1	0	0	0	0
Adverse Event	3	5	0	0	0	0
Withdrawal by Subject	15	11	0	0	0	0
Lost to Follow-up	6	4	0	0	0	0
[1] Treatment arm applicable only in Treatment Period 2 and Extension Period; [2] 12 patients did not proceed into Treatment Period 2; [3] 11 patients did not proceed into Treatment Period 2
Period Title: TREATMENT PERIOD 2
Started	0 [1]	0 [1]	63 [2]	127 [2]	63 [3]	126 [3]
Completed	0	0	57	116	59	112
Not Completed	0	0	6	11	4	14
Reason Not Completed
Non compliance study medication	0	0	0	0	0	1
Lack of Efficacy	0	0	2	6	3	2
Pregnancy	0	0	0	0	0	1
Death	0	0	0	0	0	1
Adverse Event	0	0	0	4	0	1
Withdrawal by Subject	0	0	3	1	1	7
Lost to Follow-up	0	0	1	0	0	1
[1] Treatment arm applicable for Treatment Period 1 only (patients re-randomized in Treatment Period 2); [2] Patients re-randomized from "Humira ® adalimumab" treatment arm in Treatment Period 1; [3] Patients re-randomized from "GP2017 adalimumab" treatment arm in Treatment Period 1
Period Title: EXTENSION PERIOD
Started	0	0	52 [1]	109 [2]	56 [3]	106 [4]
Completed	0	0	47	104	50	100
Not Completed	0	0	5	5	6	6
Reason Not Completed
New therapy for study indication	0	0	0	0	1	1
Lack of Efficacy	0	0	1	3	1	1
Adverse Event	0	0	2	0	1	0
Withdrawal by Subject	0	0	2	2	2	2
Non-compliance with study indication	0	0	0	0	1	0
Lost to Follow-up	0	0	0	0	0	2
[1] 5 patients did not proceed from Treatment Period 2 into Extension Period; [2] 7 patients did not proceed from Treatment Period 2 into Extension Period; [3] 3 patients did not proceed from Treatment Period 2 into Extension Period; [4] 6 patients did not proceed from Treatment Period 2 into Extension Period

Baseline Characteristics

Arm/Group Title		GP2017 Adalimumab	Humira ® Adalimumab	Total
Arm/Group Description		Solution for subcutaneous (s.c.) injection in pre-filled syringe. Study drug is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1).	Solution for subcutaneous (s.c.) injection in pre-filled syringe. Study drug is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1).	Total of all reporting groups
Overall Number of Baseline Participants		231	234	465
Baseline Analysis Population Description		The Full analysis set (FAS) consists of all randomized patients to whom a study treatment was assigned.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	231 participants	234 participants	465 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	205 88.7%	208 88.9%	413 88.8%
	>=65 years	26 11.3%	26 11.1%	52 11.2%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	231 participants	234 participants	465 participants
		45.6 (14.16)	46.9 (14.09)	46.3 (14.12)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	231 participants	234 participants	465 participants
	Female	89 38.5%	92 39.3%	181 38.9%
	Male	142 61.5%	142 60.7%	284 61.1%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	231 participants	234 participants	465 participants
United States		188	190	378
Europe		43	44	87

Outcome Measures

1. Primary Outcome

Title	PASI 75 Response Rate at Week 16 - GP2017 Adalimumab vs Humira ® Adalimumab
Description	The primary variable was the PASI75 response rate at Week 16, defined as the proportion of patients achieving a reduction of 75% or more of the PASI score at Week 16 compared with baseline.
Time Frame	At Week 16 only

Outcome Measure Data

Analysis Population Description

The Per-protocol analysis set (PPS) consists of patients who completed the study up to Week 16 and had no major protocol deviations or additional exclusion criteria up to and including Week 16.

Arm/Group Title	GP2017 Adalimumab	Humira ® Adalimumab
Arm/Group Description:	Solution for subcutaneous (s.c.) injection in pre-filled syringe. Study drug is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1).	Solution for subcutaneous (s.c.) injection in pre-filled syringe. Study drug is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1).
Overall Number of Participants Analyzed	197	196
Measure Type: Number; Unit of Measure: percent of participants
	66.8	65.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GP2017 Adalimumab, Humira ® Adalimumab
	Comments	[Not Specified]
	Type of Statistical Test	Equivalence
	Comments	Adjusted response rates were estimated using a logistic regression model including treatment, body weight strata, region and prior systemic therapy. The 95% CI for the rate difference was derived based on the normal approximation and standard error computed using the delta method.To conclude equivalent efficacy, the 95% CI had to be entirely within the interval [-18%, 18%].
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 95%; -7.46 to 11.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.75
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Mean Percent Change From Baseline in PASI Score up to Week 16 (MMRM)
Description	The key secondary efficacy variable was the percentage change from baseline in PASI score at each visit up to Week 16.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

The Per-protocol analysis set (PPS) consists of patients who completed the study up to Week 16 and had no major protocol deviations or additional exclusion criteria up to and including Week 16.

Arm/Group Title	GP2017 Adalimumab	Humira ® Adalimumab
Arm/Group Description:	Solution for subcutaneous (s.c.) injection in pre-filled syringe. Study drug is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1).	Solution for subcutaneous (s.c.) injection in pre-filled syringe. Study drug is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1).
Overall Number of Participants Analyzed	197	196
Least Squares Mean (Standard Error); Unit of Measure: percentage change from baseline
	-60.7 (1.54)	-61.5 (1.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GP2017 Adalimumab, Humira ® Adalimumab
	Comments	[Not Specified]
	Type of Statistical Test	Equivalence
	Comments	LS means, SE and 95% CI were estimated by a Mixed Model Repeated Measures (MMRM) model with treatment, visit, treatment-by-visit interaction, body weight strata, region and prior systemic therapy, as fixed factors and baseline PASI score as covariate. Therapeutic equivalence in terms of the % change from baseline in PASI score was to be determined if the 95% CI for the difference between GP2017 and Humira treatment was contained within the interval [-15%; 15%].
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; -3.15 to 4.84
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.03
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Mean ATE of Percent Change From Baseline in PASI Score up to Week 16 (ANCOVA)
Description	The key secondary efficacy variable was the average treatment effect (ATE) which is the weighted average of % change from baseline in PASI scores between Week 1 and Week 16 (weights based on the time interval between two consecutive visits).
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

The Per-protocol analysis set (PPS) consists of patients who completed the study up to Week 16 and had no major protocol deviations or additional exclusion criteria up to and including Week 16.

Arm/Group Title	GP2017 Adalimumab	Humira ® Adalimumab
Arm/Group Description:	Solution for subcutaneous (s.c.) injection in pre-filled syringe. Study drug is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1).	Solution for subcutaneous (s.c.) injection in pre-filled syringe. Study drug is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1).
Overall Number of Participants Analyzed	197	196
Least Squares Mean (Standard Error); Unit of Measure: percentage change from baseline
	-59.7 (1.59)	60.8 (1.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GP2017 Adalimumab, Humira ® Adalimumab
	Comments	[Not Specified]
	Type of Statistical Test	Equivalence
	Comments	LSM, SE and 95% CI were estimated using an ANCOVA model with treatment, body weight strata, region and prior systemic therapy as fixed effects and baseline PASI score as covariate. Therapeutic equivalence in terms of the % change from baseline in PASI score was to be determined if the 95% CI for the difference between GP2017 and Humira was contained within the interval [−15%; 15%].
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; -2.78 to 5.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.0
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	PASI 50, PASI 75, PASI 90 and PASI 100 Response Rates
Description	Proportion of patients achieving PASI 50, 75, 90 and 100 at Week 17 (end of Treatment Period 1)
Time Frame	At Week 17 only

Outcome Measure Data

Analysis Population Description

The Per-protocol analysis set (PPS) consists of patients who completed the study up to Week 16 and had no major protocol deviations or additional exclusion criteria up to and including Week 16.

Arm/Group Title	GP2017 Adalimumab	Humira ® Adalimumab
Arm/Group Description:	Solution for subcutaneous (s.c.) injection in pre-filled syringe. Study drug is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1).	Solution for subcutaneous (s.c.) injection in pre-filled syringe. Study drug is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1).
Overall Number of Participants Analyzed	197	196
Measure Type: Number; Unit of Measure: percent of participants
% of patients achieving PASI50 at Week 17	93.2	92.8
% of patients achieving PASI75 at Week 17	71.4	68.6
% of patients achieving PASI90 at Week 17	51.6	44.8
% of patients achieving PASI100 at Week 17	21.9	16.5

5. Secondary Outcome

Title	PASI 50, PASI75, PASI 90 and PASI100 Response Rates
Description	Proportion of Patients Achieving PASI 50, 75, 90 and 100 at Week 35 (end of Treatment Period 2)
Time Frame	At Week 35 only

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Humira ® Adalimumab Switched	Humira ® Adalimumab Continued	GP2017 Adalimumab Switched	GP2017 Adalimumab Continued
Arm/Group Description:	Humira is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1). Alternating treatment between GP2017/Humira ®/GP2017 subcutaneous (s.c.) injection of 40mg study drug (Treatment Period 2 / Week 17 until Week 35). Humira ® subcutaneous (s.c.) injection of 40mg study drug (Extension Period / Week 35 until Week 51).	Humira is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose until Week 51.	GP2017 is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1). Alternating treatment between Humira ®/GP2017/Humira ® subcutaneous (s.c.) injection of 40mg study drug (Treatment Period 2 / Week 17 until Week 35). GP2017 40mg subcutaneous (s.c.) injection of 40mg study drug (Extension Period / Week 35 until Week 51).	GP2017 is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose until Week 51.
Overall Number of Participants Analyzed	51	115	55	105
Measure Type: Number; Unit of Measure: percent of participants
% of patients achieving PASI50 at Week 35	95.9	96.4	94.1	96.1
% of patients achieving PASI75 at Week 35	73.5	73.6	70.6	74.5
% of patients achieving PASI90 at Week 35	53.1	52.7	62.7	61.8
% of patients achieving PASI100 at Week 35	28.6	30.9	35.3	33.3

6. Secondary Outcome

Title	PASI 50, PASI75, PASI 90 and PASI100 Response Rates
Description	Proportion of Patients Achieving PASI 50, 75, 90 and 100 at Week 51 (Entire Study)
Time Frame	At Week 51 only

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Humira ® Adalimumab Switched	Humira ® Adalimumab Continued	GP2017 Adalimumab Switched	GP2017 Adalimumab Continued
Arm/Group Description:	Humira is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1). Alternating treatment between GP2017/Humira ®/GP2017 subcutaneous (s.c.) injection of 40mg study drug (Treatment Period 2 / Week 17 until Week 35). Humira ® subcutaneous (s.c.) injection of 40mg study drug (Extension Period / Week 35 until Week 51).	Humira is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose until Week 51.	GP2017 is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1). Alternating treatment between Humira ®/GP2017/Humira ® subcutaneous (s.c.) injection of 40mg study drug (Treatment Period 2 / Week 17 until Week 35). GP2017 40mg subcutaneous (s.c.) injection of 40mg study drug (Extension Period / Week 35 until Week 51).	GP2017 is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose until Week 51.
Overall Number of Participants Analyzed	51	115	55	105
Measure Type: Number; Unit of Measure: percent of participants
% of patients achieving PASI50 at Week 51	95.3	93.9	87.5	95.9
% of patients achieving PASI75 at Week 51	76.7	79.6	75.0	84.5
% of patients achieving PASI90 at Week 51	48.8	51.0	60.4	62.9
% of patients achieving PASI100 at Week 51	25.6	29.6	31.3	35.1

7. Secondary Outcome

Title	IGA Response Rate
Description	Proportion of patients achieving a score of 0 (“clear”) or 1 (“almost clear”) or improved by at least 2 points of the IGA scale compared to baseline at Week 17.
Time Frame	At Week 17 only

Outcome Measure Data

Analysis Population Description

The Per-protocol analysis set (PPS) consists of patients who completed the study up to Week 16 and had no major protocol deviations or additional exclusion criteria up to and including Week 16.

Arm/Group Title	GP2017 Adalimumab	Humira ® Adalimumab
Arm/Group Description:	Study arm with intervention being studied in the protocol. Adalimumab Solution for subcutaneous injection with an initial dose of 80 mg s.c. in Week 0, followed by 40 mg s.c. eow, starting at Week 1 and ending at Week 51. GP2017 Adalimumab	Humira® Adalimumab as a subcutaneous injection with an initial dose of 80 mg s.c. in Week 0, followed by 40 mg s.c. eow, starting at Week 1 and ending at Week 51. Humira ® Adalimumab
Overall Number of Participants Analyzed	197	196
Measure Type: Number; Unit of Measure: percent of participants
	53.6	53.6

8. Secondary Outcome

Title	IGA Response Rate
Description	Proportion of patients achieving a score of 0 (“clear”) or 1 (“almost clear”) or improved by at least 2 points of the IGA scale compared to baseline at Week 51
Time Frame	At Week 35 only

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Humira ® Adalimumab Switched	Humira ® Adalimumab Continued	GP2017 Adalimumab Switched	GP2017 Adalimumab Continued
Arm/Group Description:	Humira is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1). Alternating treatment between GP2017/Humira ®/GP2017 subcutaneous (s.c.) injection of 40mg study drug (Treatment Period 2 / Week 17 until Week 35). Humira ® subcutaneous (s.c.) injection of 40mg study drug (Extension Period / Week 35 until Week 51).	Humira is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose until Week 51.	GP2017 is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1). Alternating treatment between Humira ®/GP2017/Humira ® subcutaneous (s.c.) injection of 40mg study drug (Treatment Period 2 / Week 17 until Week 35). GP2017 40mg subcutaneous (s.c.) injection of 40mg study drug (Extension Period / Week 35 until Week 51).	GP2017 is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose until Week 51.
Overall Number of Participants Analyzed	51	115	55	105
Measure Type: Number; Unit of Measure: percent of participants
	59.2	58.2	58.8	58.8

9. Secondary Outcome

Title	IGA Response Rate
Description	Proportion of patients achieving a score of 0 (“clear”) or 1 (“almost clear”) or improved by at least 2 points of the IGA scale compared to baseline at Week 51
Time Frame	At Week 51 only

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Humira ® Adalimumab Switched	Humira ® Adalimumab Continued	GP2017 Adalimumab Switched	GP2017 Adalimumab Continued
Arm/Group Description:	Humira is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1). Alternating treatment between GP2017/Humira ®/GP2017 subcutaneous (s.c.) injection of 40mg study drug (Treatment Period 2 / Week 17 until Week 35). Humira ® subcutaneous (s.c.) injection of 40mg study drug (Extension Period / Week 35 until Week 51).	Humira is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose until Week 51.	GP2017 is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1). Alternating treatment between Humira ®/GP2017/Humira ® subcutaneous (s.c.) injection of 40mg study drug (Treatment Period 2 / Week 17 until Week 35). GP2017 40mg subcutaneous (s.c.) injection of 40mg study drug (Extension Period / Week 35 until Week 51).	GP2017 is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose until Week 51.
Overall Number of Participants Analyzed	51	115	55	105
Measure Type: Number; Unit of Measure: percent of participants
	46.5	55.1	58.3	59.8

10. Secondary Outcome

Title	DLQI
Description	Proportion of patients reporting a DLQI of 0 or 1 (no effect at all on patient's life)
Time Frame	At Week 17 only

Outcome Measure Data

Analysis Population Description

The Per-protocol analysis set (PPS) consists of patients who completed the study up to Week 16 and had no major protocol deviations or additional exclusion criteria up to and including Week 16.

Arm/Group Title	GP2017 Adalimumab	Humira ® Adalimumab
Arm/Group Description:	Solution for subcutaneous (s.c.) injection in pre-filled syringe. Study drug is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1).	Solution for subcutaneous (s.c.) injection in pre-filled syringe. Study drug is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1).
Overall Number of Participants Analyzed	197	196
Measure Type: Number; Unit of Measure: % of patients with DLQI of 0 or 1
	50.5	48.4

11. Secondary Outcome

Title	DLQI
Description	Proportion of patients reporting a DLQI of 0 or 1 (no effect at all on patient's life)
Time Frame	At Week 35 only

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Humira ® Adalimumab Switched	Humira ® Adalimumab Continued	GP2017 Adalimumab Switched	GP2017 Adalimumab Continued
Arm/Group Description:	Humira is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1). Alternating treatment between GP2017/Humira ®/GP2017 subcutaneous (s.c.) injection of 40mg study drug (Treatment Period 2 / Week 17 until Week 35). Humira ® subcutaneous (s.c.) injection of 40mg study drug (Extension Period / Week 35 until Week 51).	Humira is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose until Week 51.	GP2017 is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1). Alternating treatment between Humira ®/GP2017/Humira ® subcutaneous (s.c.) injection of 40mg study drug (Treatment Period 2 / Week 17 until Week 35). GP2017 40mg subcutaneous (s.c.) injection of 40mg study drug (Extension Period / Week 35 until Week 51).	GP2017 is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose until Week 51.
Overall Number of Participants Analyzed	51	115	55	105
Measure Type: Number; Unit of Measure: % of patients with DLQI of 0 or 1
	49.0	54.5	52.9	55.9

12. Secondary Outcome

Title	DLQI
Description	Proportion of patients reporting a DLQI of 0 or 1 (no effect at all on patient's life)
Time Frame	At Week 51 only

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Humira ® Adalimumab Switched	Humira ® Adalimumab Continued	GP2017 Adalimumab Switched	GP2017 Adalimumab Continued
Arm/Group Description:	Humira is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1). Alternating treatment between GP2017/Humira ®/GP2017 subcutaneous (s.c.) injection of 40mg study drug (Treatment Period 2 / Week 17 until Week 35). Humira ® subcutaneous (s.c.) injection of 40mg study drug (Extension Period / Week 35 until Week 51).	Humira is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose until Week 51.	GP2017 is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1). Alternating treatment between Humira ®/GP2017/Humira ® subcutaneous (s.c.) injection of 40mg study drug (Treatment Period 2 / Week 17 until Week 35). GP2017 40mg subcutaneous (s.c.) injection of 40mg study drug (Extension Period / Week 35 until Week 51).	GP2017 is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose until Week 51.
Overall Number of Participants Analyzed	51	115	55	105
Measure Type: Number; Unit of Measure: % of patients with DLQI of 0 or 1
	48.8	55.6	54.2	59.8

13. Secondary Outcome

Title	ADA Formation Against GP2017 Adalimumab and Humira® Adalimumab From Randomization Until Week 17
Description	Proportion of patients with at least one confirmed positive anti-drug antibodies (ADA) response to adalimumab from Randomization to Week 17. Patients with ADA positive results at baseline were excluded from subsequent results.
Time Frame	At Week 17 only

Outcome Measure Data

Analysis Population Description

The Safety analysis set (SAF) includes all patients who received at least one dose of study treatment during Treatment Period 1. Patients were analyzed according to the treatment received.

Arm/Group Title	GP2017 Adalimumab	Humira ® Adalimumab
Arm/Group Description:	Solution for subcutaneous (s.c.) injection in pre-filled syringe. Study drug is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1).	Solution for subcutaneous (s.c.) injection in pre-filled syringe. Study drug is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1).
Overall Number of Participants Analyzed	231	234
Measure Type: Number; Unit of Measure: % patients with at least 1 ADA+ sample
	36.8	34.1

14. Secondary Outcome

Title	ADA Formation Against GP2017 Adalimumab and Humira® Adalimumab From Randomization Until Week 51
Description	Proportion of patients with at least one confirmed positive anti-drug antibodies (ADA) response to adalimumab from Randomization to Week 51. Patients with ADA positive results at baseline were excluded from subsequent results.
Time Frame	At Week 51 only

Outcome Measure Data

Analysis Population Description

The Safety analysis set (SAF) includes all patients who received at least one dose of study treatment during Treatment Period 1. Patients were analyzed according to the treatment received.

Arm/Group Title	Humira ® Adalimumab Switched	Humira ® Adalimumab Continued	GP2017 Adalimumab Switched	GP2017 Adalimumab Continued
Arm/Group Description:	Humira is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1). Alternating treatment between GP2017/Humira ®/GP2017 subcutaneous (s.c.) injection of 40mg study drug (Treatment Period 2 / Week 17 until Week 35). Humira ® subcutaneous (s.c.) injection of 40mg study drug (Extension Period / Week 35 until Week 51).	Humira is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose until Week 51.	GP2017 is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1). Alternating treatment between Humira ®/GP2017/Humira ® subcutaneous (s.c.) injection of 40mg study drug (Treatment Period 2 / Week 17 until Week 35). GP2017 40mg subcutaneous (s.c.) injection of 40mg study drug (Extension Period / Week 35 until Week 51).	GP2017 is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose until Week 51.
Overall Number of Participants Analyzed	63	127	63	126
Measure Type: Number; Unit of Measure: % patients with at least 1 ADA+ sample
	39.3	45.1	46.7	35.8

Adverse Events

Time Frame	Treatment emergent adverse events (TEAEs) are reported from Day 1 until the end of study (Week 51)
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Humira ® Adalimumab Switched		Humira ® Adalimumab Continued		GP2017 Adalimumab Switched		GP2017 Adalimumab Continued
Arm/Group Description	Humira is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1). Alternating treatment between GP2017/Humira ®/GP2017 subcutaneous (s.c.) injection of 40mg study drug (Treatment Period 2 / Week 17 until Week 35). Humira ® subcutaneous (s.c.) injection of 40mg study drug (Extension Period / Week 35 until Week 51).		Humira is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose until Week 51.		GP2017 is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose for the first 17 weeks (Treatment Period 1). Alternating treatment between Humira ®/GP2017/Humira ® subcutaneous (s.c.) injection of 40mg study drug (Treatment Period 2 / Week 17 until Week 35). GP2017 40mg subcutaneous (s.c.) injection of 40mg study drug (Extension Period / Week 35 until Week 51).		GP2017 is administered on Day 1 with an intial dose of 80mg followed by 40mg every other week (eow) starting one week after initial dose until Week 51.
All-Cause Mortality
	Humira ® Adalimumab Switched		Humira ® Adalimumab Continued		GP2017 Adalimumab Switched		GP2017 Adalimumab Continued
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/63 (0.00%)		0/127 (0.00%)		0/63 (0.00%)		1/126 (0.79%)
Serious Adverse Events
	Humira ® Adalimumab Switched		Humira ® Adalimumab Continued		GP2017 Adalimumab Switched		GP2017 Adalimumab Continued
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/63 (9.52%)		10/127 (7.87%)		2/63 (3.17%)		4/126 (3.17%)
Cardiac disorders
Cardiomyopathy † 1	0/63 (0.00%)	0	0/127 (0.00%)	0	0/63 (0.00%)	0	1/126 (0.79%)	1
Coronary artery disease † 1	0/63 (0.00%)	0	1/127 (0.79%)	1	0/63 (0.00%)	0	0/126 (0.00%)	0
Gastrointestinal disorders
Abdominall pain † 1	0/63 (0.00%)	0	1/127 (0.79%)	1	0/63 (0.00%)	0	0/126 (0.00%)	0
Vomiting † 1	0/63 (0.00%)	0	1/127 (0.79%)	1	0/63 (0.00%)	0	0/126 (0.00%)	0
General disorders
Chest pain † 1	0/63 (0.00%)	0	1/127 (0.79%)	1	0/63 (0.00%)	0	0/126 (0.00%)	0
Non-cardiac chest pain † 1	1/63 (1.59%)	1	0/127 (0.00%)	0	0/63 (0.00%)	0	0/126 (0.00%)	0
Pyrexia † 1	1/63 (1.59%)	1	0/127 (0.00%)	0	0/63 (0.00%)	0	0/126 (0.00%)	0
Swelling † 1	1/63 (1.59%)	1	0/127 (0.00%)	0	0/63 (0.00%)	0	0/126 (0.00%)	0
Infections and infestations
Pneumonia † 1	2/63 (3.17%)	2	1/127 (0.79%)	1	0/63 (0.00%)	0	0/126 (0.00%)	0
Pneumonia necrotizing † 1	0/63 (0.00%)	0	1/127 (0.79%)	1	0/63 (0.00%)	0	0/126 (0.00%)	0
Pulmonary tuberculosis † 1	0/63 (0.00%)	0	1/127 (0.79%)	1	0/63 (0.00%)	0	0/126 (0.00%)	0
Pyelonephritis † 1	0/63 (0.00%)	0	0/127 (0.00%)	0	0/63 (0.00%)	0	1/126 (0.79%)	1
Sepsis † 1	0/63 (0.00%)	0	1/127 (0.79%)	1	0/63 (0.00%)	0	0/126 (0.00%)	0
Musculoskeletal and connective tissue disorders
Joint effusion † 1	1/63 (1.59%)	1	0/127 (0.00%)	0	0/63 (0.00%)	0	0/126 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma † 1	1/63 (1.59%)	1	1/127 (0.79%)	1	1/63 (1.59%)	1	1/126 (0.79%)	1
Adenocarcinoma of colon † 1	0/63 (0.00%)	0	1/127 (0.79%)	1	0/63 (0.00%)	0	0/126 (0.00%)	0
Chronic lymphocytic leukaemia † 1	0/63 (0.00%)	0	1/127 (0.79%)	1	0/63 (0.00%)	0	0/126 (0.00%)	0
Prostate cancer † 1	0/63 (0.00%)	0	0/127 (0.00%)	0	1/63 (1.59%)	1	0/126 (0.00%)	0
Psychiatric disorders
Completed suicide † 1	0/63 (0.00%)	0	0/127 (0.00%)	0	0/63 (0.00%)	0	1/126 (0.79%)	1
Schizoaffective disorder † 1	0/63 (0.00%)	0	0/127 (0.00%)	0	1/63 (1.59%)	1	0/126 (0.00%)	0
Suicide attempt † 1	0/63 (0.00%)	0	1/127 (0.79%)	1	0/63 (0.00%)	0	0/126 (0.00%)	0
Renal and urinary disorders
Renal colic † 1	1/63 (1.59%)	2	0/127 (0.00%)	0	0/63 (0.00%)	0	0/126 (0.00%)	0
Renal haematoma † 1	0/63 (0.00%)	0	1/127 (0.79%)	1	0/63 (0.00%)	0	0/126 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain † 1	0/63 (0.00%)	0	1/127 (0.79%)	1	0/63 (0.00%)	0	0/126 (0.00%)	0
1 Term from vocabulary, MedDRA version 19.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	3%
	Humira ® Adalimumab Switched		Humira ® Adalimumab Continued		GP2017 Adalimumab Switched		GP2017 Adalimumab Continued
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/63 (63.49%)		85/127 (66.93%)		47/63 (74.60%)		84/126 (66.67%)
Blood and lymphatic system disorders
Thrombocytopenia † 1	0/63 (0.00%)	0	3/127 (2.36%)	5	2/63 (3.17%)	2	1/126 (0.79%)	1
Neutropenia † 1	2/63 (3.17%)	2	1/127 (0.79%)	1	0/63 (0.00%)	0	1/126 (0.79%)	1
Gastrointestinal disorders
Diarrhea † 1	2/63 (3.17%)	2	7/127 (5.51%)	7	2/63 (3.17%)	2	2/126 (1.59%)	2
Toothache † 1	0/63 (0.00%)	0	4/127 (3.15%)	5	3/63 (4.76%)	3	4/126 (3.17%)	4
Nausea † 1	2/63 (3.17%)	3	4/127 (3.15%)	5	1/63 (1.59%)	1	3/126 (2.38%)	4
Dental caries † 1	0/63 (0.00%)	0	5/127 (3.94%)	5	0/63 (0.00%)	0	2/126 (1.59%)	2
Constipation † 1	1/63 (1.59%)	1	4/127 (3.15%)	6	0/63 (0.00%)	0	1/126 (0.79%)	1
Gastrooesophageal reflux disease † 1	0/63 (0.00%)	0	4/127 (3.15%)	4	0/63 (0.00%)	0	0/126 (0.00%)	0
Abdominal discomfort † 1	2/63 (3.17%)	2	0/127 (0.00%)	0	1/63 (1.59%)	1	0/126 (0.00%)	0
Food poisoning † 1	0/63 (0.00%)	0	0/127 (0.00%)	0	2/63 (3.17%)	3	0/126 (0.00%)	0
General disorders
Fatigue † 1	1/63 (1.59%)	1	7/127 (5.51%)	8	4/63 (6.35%)	5	3/126 (2.38%)	3
Injection site erythema † 1	0/63 (0.00%)	0	3/127 (2.36%)	3	5/63 (7.94%)	14	6/126 (4.76%)	8
Injection site bruising † 1	2/63 (3.17%)	2	3/127 (2.36%)	3	0/63 (0.00%)	0	1/126 (0.79%)	1
Injection site pain † 1	1/63 (1.59%)	1	2/127 (1.57%)	2	2/63 (3.17%)	15	1/126 (0.79%)	1
Injection site pruritus † 1	1/63 (1.59%)	1	1/127 (0.79%)	2	2/63 (3.17%)	2	0/126 (0.00%)	0
Injection site induration † 1	0/63 (0.00%)	0	0/127 (0.00%)	0	2/63 (3.17%)	2	0/126 (0.00%)	0
Immune system disorders
Seasonal allergy † 1	1/63 (1.59%)	2	5/127 (3.94%)	5	1/63 (1.59%)	1	4/126 (3.17%)	4
Infections and infestations
Nasopharyngitis † 1	7/63 (11.11%)	7	16/127 (12.60%)	17	8/63 (12.70%)	12	12/126 (9.52%)	23
Upper respiratory tract infection † 1	5/63 (7.94%)	5	11/127 (8.66%)	14	3/63 (4.76%)	3	12/126 (9.52%)	17
Sinusitis † 1	2/63 (3.17%)	2	7/127 (5.51%)	8	3/63 (4.76%)	3	11/126 (8.73%)	13
Bronchitis † 1	3/63 (4.76%)	4	1/127 (0.79%)	1	2/63 (3.17%)	2	7/126 (5.56%)	7
Viral upper respiratory tract infection † 1	2/63 (3.17%)	2	2/127 (1.57%)	2	3/63 (4.76%)	3	3/126 (2.38%)	4
Urinary tract infection † 1	1/63 (1.59%)	1	2/127 (1.57%)	2	1/63 (1.59%)	1	5/126 (3.97%)	6
Gatroenteritis viral † 1	2/63 (3.17%)	2	3/127 (2.36%)	3	2/63 (3.17%)	2	1/126 (0.79%)	1
Gastroenteritis † 1	2/63 (3.17%)	2	2/127 (1.57%)	2	0/63 (0.00%)	0	2/126 (1.59%)	2
Influenza † 1	2/63 (3.17%)	2	1/127 (0.79%)	1	2/63 (3.17%)	2	1/126 (0.79%)	1
Staphylococcal infection † 1	1/63 (1.59%)	1	1/127 (0.79%)	1	2/63 (3.17%)	2	0/126 (0.00%)	0
Vulvovaginal mycotic infection † 1	2/63 (3.17%)	3	1/127 (0.79%)	1	0/63 (0.00%)	0	1/126 (0.79%)	1
Injury, poisoning and procedural complications
Muscle strain † 1	3/63 (4.76%)	3	1/127 (0.79%)	1	1/63 (1.59%)	1	1/126 (0.79%)	1
Ligament sprain † 1	2/63 (3.17%)	2	2/127 (1.57%)	2	0/63 (0.00%)	0	1/126 (0.79%)	1
Investigations
Gamma-glutamyltransferase increased † 1	0/63 (0.00%)	0	2/127 (1.57%)	2	4/63 (6.35%)	4	1/126 (0.79%)	1
Alanine aminotransferase increased † 1	0/63 (0.00%)	0	2/127 (1.57%)	2	3/63 (4.76%)	3	0/126 (0.00%)	0
Weight decreased † 1	1/63 (1.59%)	1	1/127 (0.79%)	1	2/63 (3.17%)	2	1/126 (0.79%)	1
Aspartate aminotransferase increased † 1	0/63 (0.00%)	0	0/127 (0.00%)	0	3/63 (4.76%)	3	1/126 (0.79%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 1	3/63 (4.76%)	4	3/127 (2.36%)	4	6/63 (9.52%)	6	5/126 (3.97%)	8
Back pain † 1	1/63 (1.59%)	1	5/127 (3.94%)	6	4/63 (6.35%)	4	5/126 (3.97%)	7
Pain in extremity † 1	1/63 (1.59%)	1	2/127 (1.57%)	2	3/63 (4.76%)	4	2/126 (1.59%)	2
Musculoskeletal pain † 1	2/63 (3.17%)	2	1/127 (0.79%)	1	0/63 (0.00%)	0	2/126 (1.59%)	2
Nervous system disorders
Headache † 1	7/63 (11.11%)	7	7/127 (5.51%)	8	2/63 (3.17%)	2	13/126 (10.32%)	20
Dizziness † 1	0/63 (0.00%)	0	4/127 (3.15%)	4	0/63 (0.00%)	0	4/126 (3.17%)	4
Sciatica † 1	2/63 (3.17%)	2	0/127 (0.00%)	0	0/63 (0.00%)	0	1/126 (0.79%)	1
Psychiatric disorders
Anxiety † 1	1/63 (1.59%)	1	3/127 (2.36%)	3	3/63 (4.76%)	3	1/126 (0.79%)	1
Insomnia † 1	1/63 (1.59%)	1	4/127 (3.15%)	4	1/63 (1.59%)	1	1/126 (0.79%)	1
Respiratory, thoracic and mediastinal disorders
Cough † 1	4/63 (6.35%)	4	5/127 (3.94%)	5	1/63 (1.59%)	1	2/126 (1.59%)	3
Oropharyngeal pain † 1	3/63 (4.76%)	3	3/127 (2.36%)	3	1/63 (1.59%)	1	2/126 (1.59%)	4
Sinus congestion † 1	0/63 (0.00%)	0	4/127 (3.15%)	4	2/63 (3.17%)	2	2/126 (1.59%)	2
Rhinitis allergic † 1	0/63 (0.00%)	0	1/127 (0.79%)	1	2/63 (3.17%)	2	0/126 (0.00%)	0
Skin and subcutaneous tissue disorders
Dermatitis contact † 1	0/63 (0.00%)	0	1/127 (0.79%)	1	2/63 (3.17%)	3	4/126 (3.17%)	6
Pruritus generalised † 1	1/63 (1.59%)	1	4/127 (3.15%)	4	0/63 (0.00%)	0	0/126 (0.00%)	0
Urticaria † 1	2/63 (3.17%)	2	2/127 (1.57%)	2	0/63 (0.00%)	0	0/126 (0.00%)	0
Dermal cyst † 1	2/63 (3.17%)	2	0/127 (0.00%)	0	0/63 (0.00%)	0	0/126 (0.00%)	0
Dry skin † 1	2/63 (3.17%)	2	0/127 (0.00%)	0	0/63 (0.00%)	0	0/126 (0.00%)	0
Psoriasis † 1	2/63 (3.17%)	2	0/127 (0.00%)	0	0/63 (0.00%)	0	0/126 (0.00%)	0
Vascular disorders
Hypertension † 1	3/63 (4.76%)	3	10/127 (7.87%)	10	0/63 (0.00%)	0	2/126 (1.59%)	2
1 Term from vocabulary, MedDRA version 19.0; † Indicates events were collected by systematic assessment

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.

The Sponsor shall have the right to the first publication or presentation of the results of the study which is intended to be a joint, multi-center publication of the study results. Following the first publication, institutions and/or Principal Investigators may publish or present data or results from the study per the terms of the clinical trial agreement.

Results Point of Contact

Name/Title: Global Program Medical Director

Organization: Sandoz

Phone: +49 8024 476 ext 0

EMail: biopharma.clinicaltrials@sandoz.com

Responsible Party:	Sandoz
ClinicalTrials.gov Identifier:	NCT02016105 History of Changes
Other Study ID Numbers:	GP17-301; 2013-000747-11 ( EudraCT Number )
First Submitted:	December 14, 2013
First Posted:	December 19, 2013
Results First Submitted:	February 22, 2017
Results First Posted:	April 7, 2017
Last Update Posted:	May 30, 2017