Clinical Trial to Compare Treatment With GP2017 and Humir... | NCT02744755

ID	Type	Description	Link
2015-003433-10	EudraCT Number

Status Module

Name	Class
Hexal AG	INDUSTRY

Oversight Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
GP2017	Experimental	Group 1 will receive treatment with 40mg GP2017 (Adalimumab - GP2017) by subcutaneous injection every other week up to 24 weeks (Study Period 1) at which patients achieving at least a moderate clinical response continue treatment with 40mg GP2017 subcutaneous injection every other week up to 48 weeks (Study Period 2).	Biological: Adalimumab - GP2017
US Licensed Humira	Active Comparator	Group 2 will receive treatment with 40mg Humira® (Adalimumab - US licensed Humira®) by subcutaneous injection every other week up to 24 weeks (Study Period 1) at which patients achieving at least a moderate clinical response will be switched to treatment with 40mg GP2017 subcutaneous injection every other week up to 48 weeks (Study Period 2).	Biological: Adalimumab - US licensed Humira

Name	Type	Description	Arm Group Labels	Other Names
Adalimumab - GP2017	Biological	Adalimumab - GP2017	GP2017	GP2017

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Study Period 1: Change in DAS28-CRP Score From Baseline at Week 12 in Patients Treated With GP2017 and Patients Treated With Humira	Disease activity score (DAS) 28-CRP is based on 28-joint count (tender and swollen joints), C-reactive protein and patient's assessment of global disease activity (GDA) or general health (GH), values range from 0.96 to 10.0 while higher values mean a higher disease activity. • A DAS28-CRP value >5.1 corresponds to a high disease activity • A DAS28-CRP value between 3.2 and 5.1 corresponds to a moderate disease activity • A DAS28-CRP value between 2.6 and 3.2 corresponds to a low disease activity • A DAS28-CRP value < 2.6 corresponds to remission DAS28-CRP = 0.56 * sqrt(tender28) + 0.28* sqrt(swollen28) + 0.36 * ln(CRP+1) + 0.014 * GDA or GH + 0.96 where • tender28 and swollen28 are the number of tender and swollen joints as assessed using 28-joint count • CRP is C-reactive protein (mg/l) • GDA is the global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm	Study period 1: week 12

Secondary Outcomes

Measure	Description	Time Frame
Study Period 1: Time-weighted Averaged Change From Baseline in DAS28-CRP Until Week 24 in Patients Treated With GP2017 and With Humira	Disease activity score (DAS) 28-CRP is based on 28-joint count (tender and swollen joints), C-reactive protein and patient's assessment of global disease activity (GDA) or general health (GH), values range from 0.96 to 10.0 while higher values mean a higher disease activity. • A DAS28-CRP value >5.1 corresponds to a high disease activity • A DAS28-CRP value between 3.2 and 5.1 corresponds to a moderate disease activity • A DAS28-CRP value between 2.6 and 3.2 corresponds to a low disease activity • A DAS28-CRP value < 2.6 corresponds to remission DAS28-CRP = 0.56 * sqrt(tender28) + 0.28* sqrt(swollen28) + 0.36 * ln(CRP+1) + 0.014 * GDA or GH + 0.96 where • tender28 and swollen28 are the number of tender and swollen joints as assessed using 28-joint count • CRP is C-reactive protein (mg/l) • GDA is the global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients must have been diagnosed with RA ≥ 6 months prior to screening
Patients must have active disease, defined as DAS28-CRP ≥ 3.2 at the time of screening
Patients must have CRP levels above 5mg/l or ESR levels above the upper limits of normal
Patients must have had inadequate clinical response to MTX 10 - 25 mg/week

Exclusion Criteria:

Previous treatment with adalimumab, other anti-TNFα therapies or cell depleting agents, e.g. anti-CD20 therapy
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during treatment
Nursing (lactating) or pregnant women
History of or ongoing inflammatory or autoimmune diseases other than RA, e.g. mixed connective tissue disease, systemic lupus erythematosus etc.
Systemic corticosteroids > 7.5mg/day within 4 weeks prior to baseline
History or presence of cancer or lymphoproliferative disease other than a successfully and completely treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix and/or removed non-invasive colon polyps, with no evidence of recurrence
History of uncontrolled diabetes, unstable ischemic heart disease, congestive heart failure (New York Heart Association III-IV), active peptic ulcer disease, recent stroke (within 3 months)
Subject known to have immune deficiency, history of positive human immunodeficiency virus (HIV) status or immunocompromised for other reasons
History of clinically significant hematologic (e.g. severe anemia, leucopenia, thrombocytopenia), renal or liver disease (e.g. glomerulonephritis, fibrosis, cirrhosis, hepatitis)
History of persistent chronic infection; recurrent infection or active infections
History of tuberculosis, presence of active tuberculosis, latent tuberculosis as detected by imaging (e.g. chest X-ray, chest Computerized Tomography(CT) scan, Magnetic Resonance Imaging (MRI)) and/ or positive QuantiFERON-TB Gold test (QFT)
History or evidence of opportunistic infections, e.g. histoplasmosis, listeriosis, legionellosis
Positive serology Hepatitis B (either HBsAg or anti-HBc) or Hepatitis C (positive HCV-Ab or HCV-RNA) indicative of previous or current infections

Facility	Status	City	State	ZIP	Country	Contacts
Arizona Arthritis & Rheumatology		Mesa	Arizona	85032	United States
Sun Valley Arthritis Center Ltd.

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
33651341	Derived	Blauvelt A, Leonardi CL, Gaylis N, Jauch-Lembach J, Balfour A, Lemke L, Hachaichi S, Brueckmann I, Festini T, Wiland P. Treatment with SDZ-ADL, an Adalimumab Biosimilar, in Patients with Rheumatoid Arthritis, Psoriasis, or Psoriatic Arthritis: Results of Patient-Reported Outcome Measures from Two Phase III Studies (ADMYRA and ADACCESS). BioDrugs. 2021 Mar;35(2):229-238. doi: 10.1007/s40259-021-00470-1. Epub 2021 Mar 2.
33263165

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 1, 2017	Sep 21, 2018

Arm/Group Information

ID	Title	Description
BG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
BG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Baseline characteristics are presented for Study Period 1 Full Analysis Set (SP 1 FAS ). The SP 1 FAS is comprised of all randomized patients to whom study treatment has been assigned.

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00052.8± 12.81 BG00153.8± 12.22 BG00253.3± 12.51

Sex: Female, Male

Baseline characteristics are presented for Study Period 1 Full Analysis Set (SP 1 FAS ). The SP 1 FAS is comprised of all randomized patients to whom study treatment has been assigned.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000153 BG001

Race/Ethnicity, Customized

Baseline characteristics are presented for Study Period 1 Full Analysis Set (SP 1 FAS ). The SP 1 FAS is comprised of all randomized patients to whom study treatment has been assigned.

Count of Participants

Participants

Title

Denominators

Categories

White

Title	Measurements
	BG000152 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Study Period 1: Change in DAS28-CRP Score From Baseline at Week 12 in Patients Treated With GP2017 and Patients Treated With Humira

Disease activity score (DAS) 28-CRP is based on 28-joint count (tender and swollen joints), C-reactive protein and patient's assessment of global disease activity (GDA) or general health (GH), values range from 0.96 to 10.0 while higher values mean a higher disease activity. • A DAS28-CRP value >5.1 corresponds to a high disease activity • A DAS28-CRP value between 3.2 and 5.1 corresponds to a moderate disease activity • A DAS28-CRP value between 2.6 and 3.2 corresponds to a low disease activity • A DAS28-CRP value < 2.6 corresponds to remission DAS28-CRP = 0.56 * sqrt(tender28) + 0.28* sqrt(swollen28) + 0.36 * ln(CRP+1) + 0.014 * GDA or GH + 0.96 where • tender28 and swollen28 are the number of tender and swollen joints as assessed using 28-joint count • CRP is C-reactive protein (mg/l) • GDA is the global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm

Treatment Period 1 Per-Protocol set

Posted

Least Squares Mean

Standard Error

scores on a scale

Study period 1: week 12

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Units	Counts
Participants	OG000140 OG001144

Title

Denominators

Categories

Title	Measurements
	OG000-2.16± 0.114 OG001-2.18± 0.110

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Therapeutic equivalence in terms of change from baseline in DAS28-CRP at week 12 will be concluded if the 95% confidence interval for the LS mean difference between GP2017 and Humira is contained within the interval [-0.6; 0.6]. A mixed-model repeated measures analysis was performed for DAS28-CRP change from baseline including treatment, stratification factors, time, the interaction between time (visits) and treatment all as categorical variables, and baseline DAS28-CRP as a continuous variable.					Mean Difference (Final Values)	0.02	Standard Error of the Mean	0.129	2-Sided	95	-0.24	0.27					Equivalence

Secondary

Study Period 1: Time-weighted Averaged Change From Baseline in DAS28-CRP Until Week 24 in Patients Treated With GP2017 and With Humira

Treatment Period 1 Per-Protocol set

Posted

Least Squares Mean

Standard Error

scores on a scale

Study period 1: week 24

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017

Secondary

Study Period 1- Proportion of Patients Achieving EULAR Criterion for Remission

Proportion of patients achieving European League against Rheumatism (EULAR) remission (defined as DAS28 CRP < 2.6 )

Treatment period 1 per protocol set. Patients with data available

Posted

Count of Participants

Participants

week 4, week 12 and week 24

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Units	Counts
Participants

Secondary

Study Period 1- Proportion of Patients Achieving EULAR Criterion for Good Response

Proportion of patients achieving European League against Rheumatism (EULAR) good response (defined as DAS28<=3.2 at post-baseline assessment timepoint(s) with an improvement of >1.2 in DAS28 from baseline.)

Treatment period 1 per protocol set. Patients with data available

Posted

Count of Participants

Participants

week 4, week 12 and week 24

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Units	Counts

Secondary

Study Period 1- Proportion of Patients Achieving EULAR Criterion for Moderate Response

Proportion of patients achieving European League against Rheumatism (EULAR) moderate response (defined as DAS28<=3.2 at post-baseline assessment timepoint(s) with an improvement of >0.6 to <=1.2 from baseline or DAS28 >3.2 to <=5.1 with an improvement of >0.6 to <=1.2 or of >1.2 from baseline or DAS28 >5.1 with an improvement of >1.2 from baseline) ;

Treatment period 1 per protocol set. Patients with data available

Posted

Count of Participants

Participants

week 4, week 12 and week 24

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Secondary

Study Period 1- Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria

Proportion of patients achieving EULAR/American College of Rheumatology (EULAR/ACR) Boolean remission criteria (defined as number of tender joint count 28 <=1 and swollen joint count 28 <=1, CRP level (mg/dL) <=1 and patient's global assessment <=1 on a scale of 1-10 (corresponding to <=10 on a scale of 1-100).

Treatment period 1 per protocol set. Patients with data available

Posted

Count of Participants

Participants

week 4, week 12, week 24

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Secondary

Study Period 1: Change in DAS28-CRP and DAS28-ESR Scores From Baseline to Week 24 in Patients Treated With GP2017 and Patients Treated With Humira

DAS28-CRP is a disease activity score and defined in primary outcome measure. DAS28-ESR is the DAS28 erythrocyte sedimentation rate score.

DAS28-CRP and DAS28-ESR:

best is 0,
< 2.6 - remission,
≥ 2.6 to ≤ 3.2 - low disease activity
> 3.2 to ≤ 5.1 - moderate disease activity
> 5.1 - high disease activity

DAS28-ESR = 0.56 * sqrt(tender28) + 0.28*sqrt(swollen28) + 0.7 * ln(ESR) + 0.014 * GDA where • tender28 and swollen28 are the number of tender and swollen joints as assessed using 28-joint count • CRP is C-reactive protein (mg/l) • ESR is erythrocyte sedimentation rate (mm/h) • GDA is the global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm.Values range from 0 to 10. Higher values mean a higher disease activity.

Treatment Period 1 Per-Protocol set

Posted

Least Squares Mean

Standard Error

scores on a scale

study period 1: week 2, 4, 24

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Secondary

Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24

ACR20 response was defined if a patient fulfilled all 3 criteria below: -at least 20% improvement in tender 68 joint count

-at least 20% improvement in swollen 66 joint-count; And at least 20% improvement in at least 3 of the following 5 measures: - Patient's assessment of RA pain (visual analogue scale (VAS) 100 mm), -Patient's global assessment of disease activity (VAS 100 mm), -Physician's global assessment of disease activity (VAS 100 mm), -Patient self-assessed disability index(HAQ-DI© score), -Acute phase reactant (CRP or ESR). ACR50 and ACR70 responses were defined as ACR20 response replacing "20% improvement" by "50% improvement" and "70% improvement", respectively.

Treatment period 1 per protocol set. Patients with data available

Posted

Count of Participants

Participants

Week 4, week 12 and week 24

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Secondary

Study Period 1 - Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI©) at Weeks 4, 12 and 24;

Health assessment questionnaire (HAQ-DI) disability index ranges from 0 (best) to 3 (worst).The HAQ© was scored in accordance with the recommendation from the developers outlined in the "HAQ PACK" from Stanford University, California.

Ramey Dr, Fries JF, Singh G. in B. Spilker Quality of Life and Pharmacoleconomics in Clinical Trials, 2nd ed, The Health Assessment Questionnaire 1995 -- Status and Review. Philadelphia: Lippincott-Raven Pub., 1996, p 227 - 237.

Fries JF, Spitz P, Kraines G, Holman H. Measurement of Patient Outcome in Arthritis, Arthritis and Rheumatism, 1980, 23:137-145.

Treatment period 1 per protocol set. Patients with data available

Posted

Mean

Standard Deviation

score on a scale

Weeks 4, 12 and 24;

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Secondary

Study Period 1- Proportion of Patients Achieving HAQ-DI© in Normal Range (≤ 0.5) at Weeks 4, 12 and 24;

Health assessment questionnaire disability index (HAQ-DI©) ranges from 0 (best) to 3 (worst)

Treatment period 1 per protocol set. Patients with data available

Posted

Count of Participants

Participants

Weeks 4, 12 and 24;

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Units	Counts
Participants

Secondary

Study Period 1- Proportion of Patients Achieving HAQ-DI© Score Improvement >0.3 at Weeks 4, 12 and 24

Health assessment questionnaire (HAQ-DI©) disability index ranges from 0 (best) to 3 (worst)

Treatment period 1 per protocol set. Patients with data available

Posted

Count of Participants

Participants

Weeks 4, 12 and 24;

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Units	Counts
Participants

Secondary

Study Period 1 - Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Relative to Baseline at Weeks 4, 12 and 24 (Change From Baseline)

FACIT© fatigue scale is a 13- item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function, ranging from 0 (worst) to 52 (best).

Treatment period 1 per protocol set. Patients with data available

Posted

Mean

Standard Deviation

score on a scale

Weeks 4, 12 and 24;

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Units	Counts

Secondary

Study Period 1 - CRP (C-reactive Protein) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24

Outcome measure 13 presents changes in CRP measures in blood while Outome measure 7 presents changes in DAS28-CRP scores (calculated composite score to measure the disease activity)

Treatment period 1 per protocol set. Patients with data available

Posted

Mean

Standard Deviation

mg/L

Week 4, week 12, week 24

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Units	Counts

Secondary

Study Period 1 -ESR (Erythrocyte Sedimentation Rate) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24

Outcome measure 13 presents changes in ESR measures in blood while outcome measure 7 presents changes in DAS28-ESR scores (calculated composite score to measure the disease activity)

Treatment period 1 per protocol set. Patients with data available

Posted

Mean

Standard Deviation

mm/h

Week 4, week 12, week 24

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Units	Counts

Secondary

Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira

Incidence of injection site reactions in GP2017 and Humira

Safety Set

Posted

Count of Participants

Participants

Treatment Period 1, 24 weeks

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Units	Counts
Participants

Secondary

Study Period 1 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 or Humira (Positive Patients)

Frequency of patients having anti-drug antibody (ADA) during 24 weeks

Safety Set

Posted

Count of Participants

Participants

baseline, week 2, week 4, week 12, week 24

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Units	Counts
Participants

Secondary

Study Period 2 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira (Positive Patients)

Frequency of patients having anti-drug antibody (ADA) during 24 weeks

Safety Set

Posted

Count of Participants

Participants

week 24, week 36, week 48

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Units	Counts
Participants

Secondary

Study Period 2 : Proportion of Patients Achieving ACR20/50/70 Response at Week 48, in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira

Treatment period 2 per protocol set. Patients with data available

Posted

Count of Participants

Participants

week 48

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Units	Counts
Participants

Secondary

Study Period 2 - Health Assessment Questionnaire-Disability Index (HAQ-DI©) Changes From Week 24 at Week 48 in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira

Health assessment questionnaire (HAQ-DI) disability index ranges from 0 (best) to 3 (worst)

Treatment period 1 per protocol set. Patients with data available

Posted

Mean

Standard Deviation

score on a scale

Weeks 48

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Units	Counts

Secondary

Study Period 2 :Proportion of Patients Treated Continuously With GP2017 and Patients Treated With GP2017 After Switch From Humira Achieving HAQ-DI© Score in Normal Range ≤0.5 at Week 48

Treatment period 2 per protocol set. Patients with data available

Posted

Count of Participants

Participants

week 48

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Units	Counts
Participants

Secondary

Study Period 2 : Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Changes From Week 24 at Week 48 in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira

Treatment period 2 per protocol set. Patients with data available

Posted

Mean

Standard Deviation

score on a scale

week 48

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Units	Counts

Secondary

Study Period 2: Changes From Week 24 at Week 48 in DAS28-CRP and DAS28-ESR Scores in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira

DAS28-CRP is a disease activity score and defined in primary outcome measure. DAS28-ESR is the DAS28 erythrocyte sedimentation rate score.

DAS28-CRP and DAS28-ESR:

best is 0,
< 2.6 - remission,
≥ 2.6 to ≤ 3.2 - low disease activity
> 3.2 to ≤ 5.1 - moderate disease activity
> 5.1 - high disease activity

DAS28-ESR = 0.56 * sqrt(tender28) + 0.28* sqrt(swollen28) + 0.7 * ln(ESR) + 0.014 * GDA where • tender28 and swollen28 are the number of tender and swollen joints as assessed using 28-joint count • CRP is C-reactive protein (mg/l) • ESR is erythrocyte sedimentation rate (mm/h) • GDA is the global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm.Values range from 0 to 10. Higher values mean a higher disease activity.

Treatment period 2 per protocol set. Patients with data available

Posted

Mean

Standard Deviation

score on a scale

week 48

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017

Secondary

Study Period 2: Incidence of Injection Site Reactions in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira

Incidence of injection site reactions

Safety Set

Posted

Count of Participants

Participants

up to 48 weeks

ID	Title	Description
OG000	GP2017	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
OG001	Humira / Switched GP2017	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Study Period 1 SP1 SAF GP2017	Study Period 1 SP1 SAF GP2017	177	5	177	83	177
EG001	Study Period 1 SP1 SAF Humira	Study Period 1 SP1 SAF Humira	176	4	176	74	176
EG002	Study Period 2 SP2 SAF Continued GP2017	Study Period 2 SP2 SAF Continued GP2017	159	4	159	28	159
EG003	Study Period 2 SP2 SAF Humira to GP2017	Study Period 2 SP2 SAF Humira to GP2017	166	6	166	26	166
EG004	Entire Study SP1 SAF GP2017	Entire study SP1 SAF GP2017	177	7	177	94	177
EG005	Entire Study SP1 SAF Humira/Switched GP2017	Entire study SP1 SAF Humira/Switched GP2017	176	10	176	80	176

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Angina pectoris	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected177 at risk EG0010 affected176 at risk EG0020 affected159 at risk EG0031 affected166 at risk EG0040 affected177 at risk EG0051 affected176 at risk
Constipation	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected177 at risk EG0010 affected176 at risk EG0021 affected159 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected177 at risk EG0010 affected176 at risk EG0020 affected159 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected177 at risk EG0010 affected176 at risk EG0020 affected159 at risk EG003
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected177 at risk EG0011 affected176 at risk EG0020 affected159 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected177 at risk EG0010 affected176 at risk EG0020 affected159 at risk EG003
Hepatitis	Hepatobiliary disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected177 at risk EG0010 affected176 at risk EG0020 affected159 at risk EG003
Bronchitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected177 at risk EG0010 affected176 at risk EG0020 affected159 at risk EG003
Diverticulitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected177 at risk EG0010 affected176 at risk EG0021 affected159 at risk EG003
Pneumonia	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected177 at risk EG0010 affected176 at risk EG0020 affected159 at risk EG003
Pneumonia bacterial	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 affected177 at risk EG0010 affected176 at risk EG0020 affected159 at risk EG003
Humerus fracture	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0000 affected177 at risk EG0011 affected176 at risk EG0020 affected159 at risk EG003
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0000 affected177 at risk EG0010 affected176 at risk EG0021 affected159 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected177 at risk EG0010 affected176 at risk EG0020 affected159 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected177 at risk EG0010 affected176 at risk EG0020 affected159 at risk EG003
Brain neoplasm benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.0)	Systematic Assessment	EG0000 affected177 at risk EG0011 affected176 at risk EG0020 affected159 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.0)	Systematic Assessment	EG0000 affected177 at risk EG0011 affected176 at risk EG0020 affected159 at risk EG003
Encephalopathy	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected177 at risk EG0010 affected176 at risk EG0021 affected159 at risk EG003
Epilepsy	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected177 at risk EG0011 affected176 at risk EG0020 affected159 at risk EG003
Hemianopia homonymous	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected177 at risk EG0011 affected176 at risk EG0020 affected159 at risk EG003
Intracranial pressure increased	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected177 at risk EG0011 affected176 at risk EG0020 affected159 at risk EG003
Uterine prolapse	Reproductive system and breast disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected177 at risk EG0010 affected176 at risk EG0020 affected159 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Leukopenia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0002 affected177 at risk EG0010 affected176 at risk EG0022 affected159 at risk EG0030 affected166 at risk EG0044 affected177 at risk EG0050 affected176 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0003 affected177 at risk EG0010 affected176 at risk EG0022 affected159 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0004 affected177 at risk EG0017 affected176 at risk EG0020 affected159 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0005 affected177 at risk EG0011 affected176 at risk EG0020 affected159 at risk EG003
Fatigue	General disorders	MedDRA (20.0)	Systematic Assessment	EG0005 affected177 at risk EG0010 affected176 at risk EG0020 affected159 at risk EG003
Injection site erythema	General disorders	MedDRA (20.0)	Systematic Assessment	EG0002 affected177 at risk EG0016 affected176 at risk EG0021 affected159 at risk EG003
Bronchitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0004 affected177 at risk EG0018 affected176 at risk EG0021 affected159 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0002 affected177 at risk EG0014 affected176 at risk EG0021 affected159 at risk EG003
Influenza	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0003 affected177 at risk EG0015 affected176 at risk EG0021 affected159 at risk EG003
Oral herpes	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0004 affected177 at risk EG0013 affected176 at risk EG0021 affected159 at risk EG003
Pharyngitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0009 affected177 at risk EG00110 affected176 at risk EG0021 affected159 at risk EG003
Sinusitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0005 affected177 at risk EG0013 affected176 at risk EG0020 affected159 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG00012 affected177 at risk EG0017 affected176 at risk EG0024 affected159 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0004 affected177 at risk EG0016 affected176 at risk EG0022 affected159 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG00026 affected177 at risk EG00116 affected176 at risk EG0024 affected159 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0002 affected177 at risk EG0013 affected176 at risk EG0020 affected159 at risk EG003
Transaminases increased	Investigations	MedDRA (20.0)	Systematic Assessment	EG0000 affected177 at risk EG0013 affected176 at risk EG0021 affected159 at risk EG003
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA (20.0)	Systematic Assessment	EG0003 affected177 at risk EG0013 affected176 at risk EG0022 affected159 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0008 affected177 at risk EG0010 affected176 at risk EG0022 affected159 at risk EG003
Rheumatoid arthritis	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0003 affected177 at risk EG0011 affected176 at risk EG0025 affected159 at risk EG003
Headache	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0007 affected177 at risk EG0015 affected176 at risk EG0022 affected159 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0002 affected177 at risk EG0011 affected176 at risk EG0023 affected159 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected177 at risk EG0013 affected176 at risk EG0020 affected159 at risk EG003
Hypertension	Vascular disorders	MedDRA (20.0)	Systematic Assessment	EG0005 affected177 at risk EG0013 affected176 at risk EG0022 affected159 at risk EG003

ID	Term
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases