Phase 3 Study of M923 and Humira® in Subjects With Chronic Plaque-type Psoriasis

Psoriasis Clinical Trial

Official title:

A Phase 3 Randomized, Double-blind, Multicenter Study to Evaluate Efficacy, Safety, and Immunogenicity of an Adalimumab Biosimilar (M923) and Humira® in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02581345
• Other study ID #: 911401
• Status: Completed
• Phase: Phase 3
• Start date: September 2015
• Est. completion date: April 4, 2017

Study information

• Verified date: October 2018
• Source: Momenta Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate efficacy, safety, and immunogenicity of a proposed adalimumab biosimilar (M923) and Humira in participants with moderate to severe chronic plaque-type psoriasis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 572
• Est. completion date: April 4, 2017
• Est. primary completion date: April 4, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Must be able to understand and communicate with the investigator and comply with the requirements of the study

2. Chronic plaque-type psoriasis diagnosed for at least 6 months before screening

3. Stable plaque psoriasis

4. History of receipt of or candidate for therapy.

5. Moderate to severe psoriasis at screening and baseline

6. Must be willing and able to self-administer SC injections or have a caregiver available to administer injections

7. Male participants of childbearing potential must employ a highly effective contraceptive measure

8. Female participants must have a negative pregnancy test; are not planning to become pregnant; and must not be lactating. Female participants must also agree to employ a highly effective contraceptive measure.

Exclusion Criteria:

1. Forms of psoriasis other than chronic plaque-type

2. Drug-induced psoriasis.

3. Other skin conditions which would interfere with assessment of psoriasis

4. Medical conditions other than psoriasis for which systemic corticosteroids were used in the last year prior to screening

5. Other inflammatory conditions other than psoriasis or psoriatic arthritis

6. Prior use of systemic tumor necrosis factor (TNF) inhibitors, or 2 or more non-TNF biologic therapies

7. Ongoing use of prohibited psoriasis treatments

8. Ongoing use of other non-psoriasis prohibited treatments

9. All other prior non-psoriasis concomitant treatments must be on a stable dose for at least 4 weeks

10. Laboratory abnormalities at screening deemed clinically significant by the investigator

11. Any condition or illness which in the opinion of the investigator or sponsor poses an unacceptable safety risk

12. History of latex allergy

13. History of or current signs or symptoms or diagnosis of a demyelinating disorder

14. History of or current Class III or IV New York Heart Association congestive heart failure

15. Signs, symptoms, or diagnosis of lymphoproliferative disorders, lymphoma, leukemia, myeloproliferative disorders, or multiple myeloma

16. Current malignancy or history of any malignancy except adequately treated or excised non metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ; no more than 3 lifetime basal cell and squamous cell carcinomas permitted

17. Chronic infections, recurrent infections; recent infection to be evaluated

18. History of or presence of human immunodeficiency virus (HIV), or Hepatitis B (HBV) or C virus (HCV)

19. History of active tuberculosis (TB) or untreated or inadequately treated latent TB.

20. Exposure to an investigational product =30 days prior to enrollment or participation in another clinical study during the course of this study

21. Participant is a family member or employee of the investigator or site staff or study team

Related Conditions & MeSH terms

• Chronic Plaque Psoriasis
• Psoriasis

Intervention

Biological:
• M923
Recombinant human immunoglobulin G subclass 1 (IgG1) monoclonal antibody specific for human tumor necrosis factor-alpha (TNF-a)
• Humira
Recombinant human immunoglobulin G subclass 1 (IgG1) monoclonal antibody specific for human tumor necrosis factor-alpha (TNF-a)

Locations

Country	Name	City	State
Bulgaria	Medical Centre Asklepii, OOD	Dupnitsa
Bulgaria	DCC Sveti Georgi EOOD	Haskovo
Bulgaria	UMHAT Dr.Georgi Stranski, EAD	Pleven
Bulgaria	DCC Sv. Georgi, EOOD	Plovdiv
Bulgaria	Department of Dermatology and Venereology, Faculty of Medicine, UMHAT Alexandrovska	Sofia
Canada	Mediprobe Research Inc	London	Ontario
Canada	Dr. David Gratton Dermatologue Inc.	Montreal	Quebec
Canada	Recherche GCP Research	Montréal	Quebec
Canada	SKDS Research Inc	Newmarket	Ontario
Canada	North Bay Dermatology Centre	North Bay	Ontario
Canada	Office of Dr. Michael Robern	Ottawa	Ontario
Canada	The Centre for Dermatology	Richmond Hill	Ontario
Canada	London Road Diagnostic Clinic and Medical Centre	Sarnia	Ontario
Canada	Centre de Recherche Dermatologique du Quebec metropolitain (CRDQ)	Ste-Foy	Quebec
Canada	K Papp Clinical Research Inc	Waterloo	Ontario
Czechia	CCBR Czech Brno, s.r.o	Brno
Czechia	Dermatologie - MUDr. HELENA KORANDOVA s.r.o.	Olomouc	Povel
Czechia	CCBR Czech a.s	Pardubice
Czechia	Clintrial s.r.o	Praha 10
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha 10
Czechia	CCBR Czech Prague s.r.o	Praha 3	Czech Republic
Czechia	Krajska zdravotni a.s. - Masarykova nemocnice v Usti nad Labem Dermatovenerologicke oddeleni	Usti nad Labem
Czechia	MUDr. Jaroslav Dragon - Kozni ordinace	Ústí nad Labem
Estonia	Parnu Hospital	Pärnu
Estonia	East Tallinn Central Hospital	Tallinn
Estonia	Medicum AS	Tallinn
Estonia	North Estonia Medical Centre Foundation	Tallinn
Estonia	Vahlberg & Pild OU	Tallinn
Estonia	Kliiniliste Uuringute Keskus (Clinical Research Centre)	Tartu
Estonia	Tartu University Hospital; Dermatology Clinic	Tartu
Germany	Praxis fuer Dermatologie und Venerologie	Dresden
Germany	Universitaetsklinikum Carl Gustav Carus TU Dresden	Dresden
Germany	Klinikum der Johann Wolfgang Goethe-Universitaet	Frankfurt am Main
Germany	Clinical Research Hamburg	Hamburg
Germany	Klinische Forschunq Schwerin GmbH	Mecklenburg	Vorpommern
Germany	Universitaetsklinikum Schleswig Holstein	Schleswig	Holstein
Latvia	Derma Clinic Riga Ltd	Riga
Latvia	Health Centre 4	Riga
Latvia	Health Centre 4	Riga
Latvia	J. Kisis Ltd	Riga
Latvia	Riga 1 st Hospital	Riga
Latvia	Ventspils Outpatient Clinic	Ventspils
Poland	Poradnia Kardiologiczna Jaroslaw Jurowiecki	Gdansk
Poland	Medica Pro Familia Sp. z o. o. S.K.A. Oddzial w Gdyni	Gdynia
Poland	NZOZ POLIMEDICA FILIA KIELCE (Niepubliczny Zaklad Opieki Zdrowotnej POLIMEDICA)	Kielce
Poland	Grazyna Pulka Specjalistyczny Osrodek ALL-MED	Krakow
Poland	Medica Pro Familia Sp. z o.o. SK.A.	Krakow
Poland	Centrum Medyczne Szpital Swietej Rodziny	Lodz
Poland	Centrum Terapii Wspolczesnej _J.M. Jasnorzewska Sp. Komandytowo-Akcyjna	Lodz
Poland	NZOZ ALL-MED Centrum Medyczne Specjalistyczne Gabinety Lekarskie	Lodz
Poland	KO-MED Centra Kliniczne Lublin II	Lublin
Poland	Medicome sp.zoo	Oswiecim
Poland	Ai Centrum Medyczne	Poznan
Poland	Centrum Badan Klinicznych S.C.	Poznan
Poland	KO-MED Centra Kliniczne Pulawy	Pulawy
Poland	Centrum Medyczne Medyk	Rzeszow
Poland	NZOZ Nasz Lekarz	Torun
Poland	Medica Pro Familia Sp. z o.o. S.K.A.	Warsaw	Mazowieckie
Poland	MTZ Clinical Research Sp z o.o.	Warsaw
Poland	KO-MED Centra Kliniczne Zamosc	Zamosc
Poland	Nzoz Polimedica	Zgierz
Slovakia	Derma therapy spol. s.r.o.	Bratislava
Slovakia	Nemocnica Kosice-Saca, a.s., 1.sukromna nemocnica	Kosice
Slovakia	Pedi-Derma s.r.o.	Kosice	Kosicky Kraj
Slovakia	Dema-beauty, s.r.o	Nitra
Slovakia	Sanare S.r.o	Svidnik
United States	Radiant Clinical Research	Anderson	South Carolina
United States	Wallace Medical Group, Inc.	Beverly Hills	California
United States	Tufts Medical Center; Inc.	Boston	Massachusetts
United States	Radiant Research; Inc.	Cincinnati	Ohio
United States	Radiant Research, Inc.	Columbus	Ohio
United States	Horizons Clinical Research Center, LLC	Denver	Colorado
United States	Encino Research Center	Encino	California
United States	Palmetto Clinical Trial Services, LLC	Fountain Inn	South Carolina
United States	Radiant Research, Inc.	Greer	South Carolina
United States	Dawes Fretzin Clinical Research Group, LLC	Indianapolis	Indiana
United States	eStudySite	La Mesa	California
United States	eStudySite	Las Vegas	Nevada
United States	Bioclinical Research Alliance; Inc	Miami	Florida
United States	Sanitas Reasearch, LLC	Miami	Florida
United States	Renstar Medical Research	Ocala	Florida
United States	eStudySite	Oceanside	California
United States	Compass Research, LLC	Orlando	Florida
United States	Radiant Research; Inc.	Overland Park	Kansas
United States	Austin Institute for Clinical Research, LLC	Pflugerville	Texas
United States	National Clinical Research-Richmond, Inc	Richmond	Virginia
United States	Clinical Trials of Texas; Inc.	San Antonio	Texas
United States	eStudySite	San Diego	California
United States	Shahram Jacobs MD, INC	Sherman Oaks	California
United States	Bay State Clinical Trials, Inc	Watertown	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Momenta Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Czechia,  Estonia,  Germany,  Latvia,  Poland,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Achieved a 75% Reduction in Psoriasis Area and Severity Index (PASI) (PASI 75) Scores at Week 16	The PASI combines assessments of the extent of body surface involvement in 4 anatomical regions (head, arms, trunk, and legs) and the severity of scaling, redness, and thickness in each region, yielding an overall score of 0 for no disease to 72 for the most severe disease. Each of the body areas was scored by itself, and then the 4 scores were combined into the final PASI score. Participants achieving PASI 75 are defined as having an improvement (reduction) of at least 75% in the Week 16 PASI score compared to the score at Baseline.	Baseline; Week 16
Secondary	Percentage of Participants With a Response of Clear or Almost Clear on the Static Physician Global Assessment (sPGA) at Week 16	The sPGA response rate was defined as the percentage of participants who had achieved a clear or almost clear response on the 6-point sPGA scale. The sPGA was the physician's determination of the participant's psoriasis lesions overall at a given time point. Overall lesions were categorized by descriptions for induration, erythema, and scaling. For the analysis of responses, the participant's psoriasis was assessed at a given time point on a 6-point scale on which 0 = cleared, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = very severe.	Week 16
Secondary	Number of Participants Achieving PASI 50 Response at Week 16	The PASI combines assessments of the extent of body surface involvement in 4 anatomical regions (head, arms, trunk, and legs) and the severity of scaling, redness, and thickness in each region, yielding an overall score of 0 for no disease to 72 for the most severe disease. Each of the body areas was scored by itself, and then the 4 scores were combined into the final PASI score. Participants achieving PASI 50 are defined as having an improvement (reduction) of at least 50% compared to Baseline.	Baseline; Week 16
Secondary	Number of Participants Achieving PASI 50 Response at Week 52 (Follow-Up Visit)	The PASI combines assessments of the extent of body surface involvement in 4 anatomical regions (head, arms, trunk, and legs) and the severity of scaling, redness, and thickness in each region, yielding an overall score of 0 for no disease to 72 for the most severe disease. Each of the body areas was scored by itself, and then the 4 scores were combined into the final PASI score. Participants achieving PASI 50 are defined as having an improvement (reduction) of at least 50% compared to Baseline.	Baseline; Week 52
Secondary	Number of Participants Achieving PASI 75 Response at Week 52 (Follow-Up Visit)	The PASI combines assessments of the extent of body surface involvement in 4 anatomical regions (head, arms, trunk, and legs) and the severity of scaling, redness, and thickness in each region, yielding an overall score of 0 for no disease to 72 for the most severe disease. Each of the body areas was scored by itself, and then the 4 scores were combined into the final PASI score. Participants achieving PASI 75 are defined as having an improvement (reduction) of at least 75% compared to Baseline.	Baseline; Week 52
Secondary	Number of Participants Achieving PASI 90 Response at Week 16	The PASI combines assessments of the extent of body surface involvement in 4 anatomical regions (head, arms, trunk, and legs) and the severity of scaling, redness, and thickness in each region, yielding an overall score of 0 for no disease to 72 for the most severe disease. Each of the body areas was scored by itself, and then the 4 scores were combined into the final PASI score. Participants achieving PASI 90 are defined as having an improvement (reduction) of at least 90% compared to Baseline.	Baseline; Week 16
Secondary	Number of Participants Achieving PASI 90 Response at Week 52 (Follow-Up Visit)	The PASI combines assessments of the extent of body surface involvement in 4 anatomical regions (head, arms, trunk, and legs) and the severity of scaling, redness, and thickness in each region, yielding an overall score of 0 for no disease to 72 for the most severe disease. Each of the body areas was scored by itself, and then the 4 scores were combined into the final PASI score. Participants achieving PASI 90 are defined as having an improvement (reduction) of at least 90% compared to Baseline.	Baseline; Week 52
Secondary	Absolute PASI Score at Baseline	The PASI combines assessments of the extent of body surface involvement in 4 anatomical regions (head, arms, trunk, and legs) and the severity of scaling, redness, and thickness in each region, yielding an overall score of 0 for no disease to 72 for the most severe disease. Each of the body areas was scored by itself, and then the 4 scores were combined into the final PASI score.	Baseline
Secondary	Absolute PASI Score at Week 16	The PASI combines assessments of the extent of body surface involvement in 4 anatomical regions (head, arms, trunk, and legs) and the severity of scaling, redness, and thickness in each region, yielding an overall score of 0 for no disease to 72 for the most severe disease. Each of the body areas was scored by itself, and then the 4 scores were combined into the final PASI score.	Week 16
Secondary	Absolute PASI Score at Week 52 (Follow-Up Visit)	The PASI combines assessments of the extent of body surface involvement in 4 anatomical regions (head, arms, trunk, and legs) and the severity of scaling, redness, and thickness in each region, yielding an overall score of 0 for no disease to 72 for the most severe disease. Each of the body areas was scored by itself, and then the 4 scores were combined into the final PASI score.	Week 52
Secondary	Percent Change From Baseline in PASI Score at Week 16	The PASI combines assessments of the extent of body surface involvement in 4 anatomical regions (head, arms, trunk, and legs) and the severity of scaling, redness, and thickness in each region, yielding an overall score of 0 for no disease to 72 for the most severe disease. Each of the body areas was scored by itself, and then the 4 scores were combined into the final PASI score. Percent change from Baseline was calculated as: (post-Baseline value - Baseline value) / (Baseline value) * 100.	Baseline; Week 16
Secondary	Percent Change From Baseline in PASI Score at Week 52 (Follow-Up Visit)	The PASI combines assessments of the extent of body surface involvement in 4 anatomical regions (head, arms, trunk, and legs) and the severity of scaling, redness, and thickness in each region, yielding an overall score of 0 for no disease to 72 for the most severe disease. Each of the body areas was scored by itself, and then the 4 scores were combined into the final PASI score. Percent change from Baseline was calculated as: (post-Baseline value - Baseline value) / (Baseline value) * 100.	Baseline; Week 52
Secondary	Health-Related Quality of Life During Treatment: Dermatology Life Quality Index (DLQI) Score at Baseline	The DLQI score was calculated by summing the individual scores of each question at a given time point, resulting in a maximum score of 30 and a minimum score of 0. The higher the score, the more quality of life is impaired. For the analysis of responses, the participant's results were assessed on a scoring scale on which 3 = very much or yes (applicable to question 7 only), 2 = a lot, 1 = a little, 0 = not at all or not relevant. Interpretation of DLQI scoring can be taken as 0 - 1 = no effect at all on participant's life, 2 - 5 = small effect on participant's life, 6 - 10 = moderate effect on participant's life, 11 - 20 = very large effect on participant's life, and 21 - 30 = extremely large effect on participant's life.	Baseline
Secondary	Health-Related Quality of Life During Treatment: DLQI Score at Week 16	The DLQI score was calculated by summing the individual scores of each question at a given time point, resulting in a maximum score of 30 and a minimum score of 0. The higher the score, the more quality of life is impaired. For the analysis of responses, the participant's results were assessed on a scoring scale on which 3 = very much or yes (applicable to question 7 only), 2 = a lot, 1 = a little, 0 = not at all or not relevant. Interpretation of DLQI scoring can be taken as 0 - 1 = no effect at all on participant's life, 2 - 5 = small effect on participant's life, 6 - 10 = moderate effect on participant's life, 11 - 20 = very large effect on participant's life, and 21 - 30 = extremely large effect on participant's life.	Week 16
Secondary	Health-Related Quality of Life During Treatment: DLQI Score at Week 48 (Completion/Termination Visit)	The DLQI score was calculated by summing the individual scores of each question at a given time point, resulting in a maximum score of 30 and a minimum score of 0. The higher the score, the more quality of life is impaired. For the analysis of responses, the participant's results were assessed on a scoring scale on which 3 = very much or yes (applicable to question 7 only), 2 = a lot, 1 = a little, 0 = not at all or not relevant. Interpretation of DLQI scoring can be taken as 0 - 1 = no effect at all on participant's life, 2 - 5 = small effect on participant's life, 6 - 10 = moderate effect on participant's life, 11 - 20 = very large effect on participant's life, and 21 - 30 = extremely large effect on participant's life.	Week 48
Secondary	Health-Related Quality of Life During Treatment: EuroQoL 5-Dimension Health Status Questionnaire (EQ-5D-5L) at Baseline	The EQ-5D-5L health score was measured on a Visual Analog Scale (VAS) anchored by 0 = "worst health you can imagine" and 100 = "best health you can imagine". Baseline was defined as the last scheduled observation prior to dosing, typically Day 1, predose.	Baseline
Secondary	Health-Related Quality of Life During Treatment: EQ-5D-5L at Week 16	The EQ-5D-5L health score was measured on a Visual Analog Scale (VAS) anchored by 0 = "worst health you can imagine" and 100 = "best health you can imagine".	Week 16
Secondary	Health-Related Quality of Life During Treatment: EQ-5D-5L at Week 48 (Completion/Termination Visit)	The EQ-5D-5L health score was measured on a Visual Analog Scale (VAS) anchored by 0 = "worst health you can imagine" and 100 = "best health you can imagine".	Week 48
Secondary	Number of Participants With Clinically Meaningful Changes in Vital Signs	Vital signs included body temperature, respiratory rate, pulse rate, systolic and diastolic blood pressure, and weight. Clinically meaningful changes were classified as such by the Investigator and reported as adverse events.	Up to Week 52
Secondary	Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline	Laboratory results included hematology [Hemoglobin, Hematocrit, Platelet count, Mean cell volume, White blood cell count (total leucocytes), Neutrophils absolute, Neutrophils, Lymphocytes absolute, Lymphocytes, Monocytes, Eosinophils absolute, and Eosinophils], chemistry (Aspartate transaminase, Alanine transaminase, Gamma glutamyl transferase, Creatine kinase, C-reactive protein, Cholesterol, Triglycerides, Total protein, Potassium, Urea, Creatinine, Phosphate, Glucose, and Uric acid) and urinalysis [Specific Gravity] parameters. Laboratory results of a few hematology (Red Blood Cell Count and Monocytes absolute), chemistry (Alkaline Phosphatase, Total bilirubin, Sodium, Chloride, and Albumin), and urinalysis (pH) parameters were not assessed at Baseline and Week 16. Clinically meaningful changes were classified as such by the Investigator and reported as adverse events.	Baseline
Secondary	Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16	Laboratory results included hematology [Hemoglobin, Hematocrit, Platelet count, Mean cell volume, White blood cell count (total leucocytes), Neutrophils absolute, Neutrophils, Lymphocytes absolute, Lymphocytes, Monocytes, Eosinophils absolute, and Eosinophils], chemistry (Aspartate transaminase, Alanine transaminase, Gamma glutamyl transferase, Creatine kinase, C-reactive protein, Cholesterol, Triglycerides, Total protein, Potassium, Urea, Creatinine, Phosphate, Glucose, and Uric acid) and urinalysis [Specific Gravity] parameters. Laboratory results of a few hematology (Red Blood Cell Count and Monocytes absolute), chemistry (Alkaline Phosphatase, Total bilirubin, Sodium, Chloride, and Albumin), and urinalysis (pH) parameters were not assessed at Baseline and Week 16. Clinically meaningful changes were classified as such by the Investigator and reported as adverse events.	Week 16
Secondary	Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit)	Laboratory results included hematology [Red Blood Cell Count, Hemoglobin, Hematocrit, Platelet count, Mean cell volume, White blood cell count (total leucocytes), Neutrophils absolute, Neutrophils, Lymphocytes absolute, Lymphocytes, Monocytes absolute, Monocytes, Eosinophils absolute, and Eosinophils], chemistry (Aspartate transaminase, Alanine transaminase, Alkaline Phosphatase, Gamma glutamyl transferase, Total bilirubin, Creatine kinase, C-reactive protein, Cholesterol, Triglycerides, Total protein, Sodium, Potassium, Chloride, Urea, Creatinine, Albumin, Phosphate, Glucose, and Uric acid) and urinalysis [pH and Specific Gravity] parameters. Clinically meaningful changes were classified as such by the Investigator and reported as adverse events.	Week 48
Secondary	Number of Participants With Clinically Significant Abnormalities in Electrocardiogram Parameters at Baseline	Clinically significant abnormalities were classified as such by the Investigator and reported as adverse events.	Baseline
Secondary	Number of Participants With Clinically Significant Abnormalities in Electrocardiogram Parameters at Week 16	Clinically significant abnormalities were classified as such by the Investigator and reported as adverse events.	Week 16
Secondary	Number of Participants With Clinically Significant Abnormalities in Electrocardiogram Parameters at Week 48 (Completion/Termination Visit)	Clinically significant abnormalities were classified as such by the Investigator and reported as adverse events.	Week 48
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	TEAEs are adverse events that occurred during or after study drug administration. For more details on adverse events please refer the safety section.	Up to Week 52
Secondary	Pharmacokinetics: Serum Concentrations by Treatment	Serum samples were collected at Baseline (Week 0, perdose), approximately 1 week (peak) after IP administration (Weeks 8 and 16), and 2 weeks after dose administration as a trough sample collected prior to the next dose administration (Weeks 17, 21, 25, 29, 37, 41).	Baseline (Week 0), Week 8, 16, 17, 21, 25, 29, 37, and 41
Secondary	Immunogenicity: Number of Participants With Anti-Drug Antibodies (ADA) at Baseline	The M923 confirmation assay was evaluated only if the EU Humira confirmation assay was negative. Overall Result: a participant was considered to be positive if a confirmed positive result was observed at any assay (including predose; if a participant had either a negative result in the screening assay or a positive result at screening followed by a negative result in all confirmation tiers, the overall result was negative. Overall Status: a participant was considered to have developed ADA or neutralizing ADAs if a confirmed positive result was observed at any time during the treatment period inclusive of the predose results; the designation of negative required either a negative screening assay or a negative confirmation result at each sampling time. The same convention applied for the neutralizing assay results.	Baseline (Week 0)
Secondary	Immunogenicity: Number of Participants With ADA at Week 16	The M923 confirmation assay was evaluated only if the EU Humira confirmation assay was negative. Overall Result: a participant was considered to be positive if a confirmed positive result was observed at any assay (including predose; if a participant had either a negative result in the screening assay or a positive result at screening followed by a negative result in all confirmation tiers, the overall result was negative. Overall Status: a participant was considered to have developed ADA or neutralizing ADAs if a confirmed positive result was observed at any time during the treatment period inclusive of the predose results; the designation of negative required either a negative screening assay or a negative confirmation result at each sampling time. The same convention applied for the neutralizing assay results.	Week 16
Secondary	Immunogenicity: Number of Participants With ADA at Week 25	The M923 confirmation assay was evaluated only if the EU Humira confirmation assay was negative. Overall Result: a participant was considered to be positive if a confirmed positive result was observed at any assay (including predose; if a participant had either a negative result in the screening assay or a positive result at screening followed by a negative result in all confirmation tiers, the overall result was negative. Overall Status: a participant was considered to have developed ADA or neutralizing ADAs if a confirmed positive result was observed at any time during the treatment period inclusive of the predose results; the designation of negative required either a negative screening assay or a negative confirmation result at each sampling time. The same convention applied for the neutralizing assay results.	Week 25
Secondary	Immunogenicity: Number of Participants With ADA at Week 52 (Completion/Termination Visit)	The M923 confirmation assay was evaluated only if the EU Humira confirmation assay was negative. Overall Result: a participant was considered to be positive if a confirmed positive result was observed at any assay (including predose; if a participant had either a negative result in the screening assay or a positive result at screening followed by a negative result in all confirmation tiers, the overall result was negative. Overall Status: a participant was considered to have developed ADA or neutralizing ADAs if a confirmed positive result was observed at any time during the treatment period inclusive of the predose results; the designation of negative required either a negative screening assay or a negative confirmation result at each sampling time. The same convention applied for the neutralizing assay results.	Week 52
Secondary	Immunogenicity: Number of Participants With ADA and nADA by Titer at Baseline	The M923 confirmation assay was evaluated only if the EU Humira confirmation assay was negative. Overall Result: a participant was considered to be positive if a confirmed positive result was observed at any assay (including predose); if a participant had either a negative result in the screening assay or a positive result at screening followed by a negative result in all confirmation tiers, the overall result was negative. Overall Status: a participant was considered to have developed ADA or neutralizing ADAs if a confirmed positive result was observed at any time during the treatment period inclusive of the predose results; the designation of negative required either a negative screening assay or a negative confirmation result at each sampling time. In confirmed positive samples, an assay was used to determine the relative titer of the ADA; a subsequent neutralizing antibodies assay was used to determine the presence of neutralizing antibodies.	Baseline (Week 0)
Secondary	Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 16	The M923 confirmation assay was evaluated only if the EU Humira confirmation assay was negative. Overall Result: a participant was considered to be positive if a confirmed positive result was observed at any assay (including predose); if a participant had either a negative result in the screening assay or a positive result at screening followed by a negative result in all confirmation tiers, the overall result was negative. Overall Status: a participant was considered to have developed ADA or neutralizing ADAs if a confirmed positive result was observed at any time during the treatment period inclusive of the predose results; the designation of negative required either a negative screening assay or a negative confirmation result at each sampling time. In confirmed positive samples, an assay was used to determine the relative titer of the ADA; a subsequent neutralizing antibodies assay was used to determine the presence of neutralizing antibodies.	Week 16
Secondary	Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25	The M923 confirmation assay was evaluated only if the EU Humira confirmation assay was negative. Overall Result: a participant was considered to be positive if a confirmed positive result was observed at any assay (including predose); if a participant had either a negative result in the screening assay or a positive result at screening followed by a negative result in all confirmation tiers, the overall result was negative. Overall Status: a participant was considered to have developed ADA or neutralizing ADAs if a confirmed positive result was observed at any time during the treatment period inclusive of the predose results; the designation of negative required either a negative screening assay or a negative confirmation result at each sampling time. In confirmed positive samples, an assay was used to determine the relative titer of the ADA; a subsequent neutralizing antibodies assay was used to determine the presence of neutralizing antibodies.	Week 25
Secondary	Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit)	The M923 confirmation assay was evaluated only if the EU Humira confirmation assay was negative. Overall Result: a participant was considered to be positive if a confirmed positive result was observed at any assay (including predose); if a participant had either a negative result in the screening assay or a positive result at screening followed by a negative result in all confirmation tiers, the overall result was negative. Overall Status: a participant was considered to have developed ADA or neutralizing ADAs if a confirmed positive result was observed at any time during the treatment period inclusive of the predose results; the designation of negative required either a negative screening assay or a negative confirmation result at each sampling time. In confirmed positive samples, an assay was used to determine the relative titer of the ADA; a subsequent neutralizing antibodies assay was used to determine the presence of neutralizing antibodies.	Week 52
Secondary	Median Time to Seroconversion	Time to seroconversion (in days) was defined as the time to the observation of the first confirmed positive ADA response. Participants with confirmed positive ADA response at baseline (Week 0 predose) were excluded.	Up to Week 52