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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Chronic Plaque Psoriasis, Psoriasis

Intervention / Treatment
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* Biological: M923
* Biological: Humira


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be able to understand and communicate with the investigator and comply with the requirements of the study Chronic plaque-type psoriasis diagnosed for at least 6 months before screening Stable plaque psoriasis History of receipt of or candidate for therapy. Moderate to severe psoriasis at screening and baseline Must be willing and able to self-administer SC injections or have a caregiver available to administer injections Male participants of childbearing potential must employ a highly effective contraceptive measure 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: Forms of psoriasis other than chronic plaque-type Drug-induced psoriasis. Other skin conditions which would interfere with assessment of psoriasis Medical conditions other than psoriasis for which systemic corticosteroids were used in the last year prior to screening Other inflammatory conditions other than psoriasis or psoriatic arthritis Prior use of systemic tumor necrosis factor (TNF) inhibitors, or 2 or more non-TNF biologic therapies Ongoing use of prohibited psoriasis treatments Ongoing use of other non-psoriasis prohibited treatments All other prior non-psoriasis concomitant treatments must be on a stable dose for at least 4 weeks Laboratory abnormalities at screening deemed clinically significant by the investigator Any condition or illness which in the opinion of the investigator or sponsor poses an unacceptable safety risk History of latex allergy History of or current signs or symptoms or diagnosis of a demyelinating disorder History of or current Class III or IV New York Heart Association congestive heart failure Signs, symptoms, or diagnosis of lymphoproliferative disorders, lymphoma, leukemia, myeloproliferative disorders, or multiple myeloma 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 Chronic infections, recurrent infections; recent infection to be evaluated History of or presence of human immunodeficiency virus (HIV), or Hepatitis B (HBV) or C virus (HCV) History of active tuberculosis (TB) or untreated or inadequately treated latent TB. Exposure to an investigational product ≤30 days prior to enrollment or participation in another clinical study during the course of this study Participant is a family member or employee of the investigator or site staff or study team

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: M923<br>Participants assigned to receive M923 | Biological: M923<br>* Recombinant human immunoglobulin G subclass 1 (IgG1) monoclonal antibody specific for human tumor necrosis factor-alpha (TNF-α)<br>* Other names: Adalimumab;|
| Active Comparator: Humira<br>Participants assigned to receive Humira | Biological: Humira<br>* Recombinant human immunoglobulin G subclass 1 (IgG1) monoclonal antibody specific for human tumor necrosis factor-alpha (TNF-α)<br>* Other names: Adalimumab;|
| Other: M923 and Humira<br>Participants assigned to receive M923 and Humira | Biological: M923<br>* Recombinant human immunoglobulin G subclass 1 (IgG1) monoclonal antibody specific for human tumor necrosis factor-alpha (TNF-α)<br>* Other names: Adalimumab;Biological: Humira<br>* Recombinant human immunoglobulin G subclass 1 (IgG1) monoclonal antibody specific for human tumor necrosis factor-alpha (TNF-α)<br>* Other names: Adalimumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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) | 
| 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 | 
| 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 | 
| 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 | 
| 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) | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Moderate to severe chronic plaque psoriasis, Psoriasis