Chronic Plaque Psoriasis, Psoriasis
Conditions
Keywords
Moderate to severe chronic plaque psoriasis, Psoriasis
Brief 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.
Interventions
Sponsors
Momenta Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved a 75% Reduction in Psoriasis Area and Severity Index (PASI) (PASI 75) Scores at Week 16 | Baseline; 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving PASI 50 Response at Week 16 | Baseline; 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. |
| Number of Participants Achieving PASI 50 Response at Week 52 (Follow-Up Visit) | Baseline; Week 52 | 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. |
| Number of Participants Achieving PASI 75 Response at Week 52 (Follow-Up Visit) | Baseline; Week 52 | 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. |
| Number of Participants Achieving PASI 90 Response at Week 16 | Baseline; 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. |
| Number of Participants Achieving PASI 90 Response at Week 52 (Follow-Up Visit) | Baseline; Week 52 | 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. |
| Absolute PASI Score at Baseline | 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. |
| Absolute PASI Score at Week 16 | 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. |
| Absolute PASI Score at Week 52 (Follow-Up Visit) | Week 52 | 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 in PASI Score at Week 16 | Baseline; 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. |
| Percent Change From Baseline in PASI Score at Week 52 (Follow-Up Visit) | Baseline; Week 52 | 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. |
| Health-Related Quality of Life During Treatment: Dermatology Life Quality Index (DLQI) Score at Baseline | 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. |
| Health-Related Quality of Life During Treatment: DLQI Score at Week 16 | 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. |
| Health-Related Quality of Life During Treatment: DLQI Score at Week 48 (Completion/Termination Visit) | Week 48 | 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. |
| Health-Related Quality of Life During Treatment: EuroQoL 5-Dimension Health Status Questionnaire (EQ-5D-5L) at Baseline | 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. |
| Health-Related Quality of Life During Treatment: EQ-5D-5L at Week 16 | 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. |
| Health-Related Quality of Life During Treatment: EQ-5D-5L at Week 48 (Completion/Termination Visit) | Week 48 | 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. |
| Number of Participants With Clinically Meaningful Changes in Vital Signs | Up to Week 52 | 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. |
| Percentage of Participants With a Response of Clear or Almost Clear on the Static Physician Global Assessment (sPGA) at Week 16 | 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. |
| Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | 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. |
| Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Week 48 | 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. |
| Number of Participants With Clinically Significant Abnormalities in Electrocardiogram Parameters at Baseline | Baseline | Clinically significant abnormalities were classified as such by the Investigator and reported as adverse events. |
| Number of Participants With Clinically Significant Abnormalities in Electrocardiogram Parameters at Week 16 | Week 16 | Clinically significant abnormalities were classified as such by the Investigator and reported as adverse events. |
| Number of Participants With Clinically Significant Abnormalities in Electrocardiogram Parameters at Week 48 (Completion/Termination Visit) | Week 48 | Clinically significant abnormalities were classified as such by the Investigator and reported as adverse events. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to Week 52 | TEAEs are adverse events that occurred during or after study drug administration. For more details on adverse events please refer the safety section. |
| Pharmacokinetics: Serum Concentrations by Treatment | Baseline (Week 0), Week 8, 16, 17, 21, 25, 29, 37, and 41 | 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). |
| Immunogenicity: Number of Participants With Anti-Drug Antibodies (ADA) at Baseline | Baseline (Week 0) | 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. |
| Immunogenicity: Number of Participants With ADA at Week 16 | 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. |
| Immunogenicity: Number of Participants With ADA at Week 25 | 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. |
| Immunogenicity: Number of Participants With ADA at Week 52 (Completion/Termination Visit) | Week 52 | 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. |
| Immunogenicity: Number of Participants With ADA and nADA by Titer at Baseline | Baseline (Week 0) | 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. |
| Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 16 | 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. |
| Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | 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. |
| Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Week 52 | 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. |
| Median Time to Seroconversion | Up to Week 52 | 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. |
| Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | 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. |
Countries
Bulgaria, Canada, Czechia, Estonia, Germany, Latvia, Poland, Slovakia, United States
Participant flow
Recruitment details
A total of 572 participants were enrolled and randomized equally into M923 and European Union reference protein product (EU RPP) arms. One participant in each arm did not receive any treatment. The 263 participants completing EU RPP treatment in Part 1 were randomized to 1 of 2 treatment arms in Part 2 (Transition and Continuous).
Participants by arm
| Arm | Count |
|---|---|
| Part 1 and Part 2: M923 Participants received 80 milligrams (mg) M923 (recombinant human immunoglobulin G subclass 1 \[IgG1\] monoclonal antibody specific for human tumor necrosis factor-alpha \[TNF-α\]) at Baseline (Week 0) and 40 mg every 2 weeks from Week 1 to Week 48 as a subcutaneous injection. | 286 |
| Part 1 and Part 2: EU RPP Participants received 80 mg European Union Reference Protein Product (EU RPP) at Baseline (Week 0) and 40 mg every 2 weeks from Week 1 to Week 16 as a subcutaneous injection. Participants from this arm were then randomized at Week 16 into either Arm: Continuous EU RPP (continued EU RPP from Weeks 17 to 48 \[last dose at Week 47\]) or Arm: Transition EU RPP (transition to M923 at Week 17; then to EU RPP at Week 25; and then to M923 at Week 37 \[last dose at Week 47\]). | 286 |
| Total | 572 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part 1: up to Week 16 | Adverse Event | 3 | 8 | 0 | 0 |
| Part 1: up to Week 16 | Did Not Receive Treatment | 1 | 1 | 0 | 0 |
| Part 1: up to Week 16 | Lost to Follow-up | 2 | 0 | 0 | 0 |
| Part 1: up to Week 16 | Physician Decision | 2 | 4 | 0 | 0 |
| Part 1: up to Week 16 | Unspecified Reason | 3 | 3 | 0 | 0 |
| Part 1: up to Week 16 | Withdrawal by Subject | 4 | 7 | 0 | 0 |
| Part 2: Week 17 to Week 47 | Adverse Event | 5 | 0 | 2 | 2 |
| Part 2: Week 17 to Week 47 | Failure to Achieve at Least a PASI 50 | 8 | 0 | 3 | 2 |
| Part 2: Week 17 to Week 47 | Lost to Follow-up | 2 | 0 | 0 | 1 |
| Part 2: Week 17 to Week 47 | Physician Decision | 3 | 0 | 2 | 1 |
| Part 2: Week 17 to Week 47 | Unspecified Reason | 2 | 0 | 1 | 1 |
| Part 2: Week 17 to Week 47 | Withdrawal by Subject | 9 | 0 | 7 | 5 |
Baseline characteristics
| Characteristic | Part 1 and Part 2: M923 | Total | Part 1 and Part 2: EU RPP |
|---|---|---|---|
| Age, Continuous | 44.6 years STANDARD_DEVIATION 12.4 | 45.0 years STANDARD_DEVIATION 12.6 | 45.5 years STANDARD_DEVIATION 12.9 |
| Number of Participants with the Indicated Static Physician's Global Assessment (sPGA) Score Almost Clear | 0 Participants | 0 Participants | 0 Participants |
| Number of Participants with the Indicated Static Physician's Global Assessment (sPGA) Score Clear | 0 Participants | 0 Participants | 0 Participants |
| Number of Participants with the Indicated Static Physician's Global Assessment (sPGA) Score Mild | 0 Participants | 0 Participants | 0 Participants |
| Number of Participants with the Indicated Static Physician's Global Assessment (sPGA) Score Moderate | 170 Participants | 352 Participants | 182 Participants |
| Number of Participants with the Indicated Static Physician's Global Assessment (sPGA) Score Severe | 103 Participants | 194 Participants | 91 Participants |
| Number of Participants with the Indicated Static Physician's Global Assessment (sPGA) Score Very Severe | 12 Participants | 24 Participants | 12 Participants |
| Psoriasis Area and Severity Index (PASI) Score | 21.24 units on a scale STANDARD_DEVIATION 9.27 | 20.70 units on a scale STANDARD_DEVIATION 8.74 | 20.16 units on a scale STANDARD_DEVIATION 8.16 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 281 Participants | 563 Participants | 282 Participants |
| Sex: Female, Male Female | 95 Participants | 195 Participants | 100 Participants |
| Sex: Female, Male Male | 191 Participants | 377 Participants | 186 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 285 | 0 / 285 | 0 / 271 | 0 / 132 | 0 / 131 |
| other Total, other adverse events | 92 / 285 | 104 / 285 | 96 / 271 | 47 / 132 | 63 / 131 |
| serious Total, serious adverse events | 4 / 285 | 7 / 285 | 10 / 271 | 10 / 132 | 8 / 131 |
Outcome results
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.
Time frame: Baseline; Week 16
Population: Per Protocol (PP) Analysis Set: subgroup of the Intent-To-Treat (ITT) Analysis Set that included all participants who did not have any deviations from the protocol deemed significant enough for exclusion from the efficacy analysis and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: M923 | Percentage of Participants Who Achieved a 75% Reduction in Psoriasis Area and Severity Index (PASI) (PASI 75) Scores at Week 16 | 80.1 percentage of participants |
| Part 1: EU RPP | Percentage of Participants Who Achieved a 75% Reduction in Psoriasis Area and Severity Index (PASI) (PASI 75) Scores at Week 16 | 79.0 percentage of participants |
90% CI: [-0.043, 0.072]
95% CI: [-0.054, 0.082]
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.
Time frame: Baseline
Population: Analysis was performed using PP Analysis Set including participants with evaluable data for part 1 and part 2 of the study are included in the analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: M923 | Absolute PASI Score at Baseline | 21.34 units on a scale | Standard Deviation 9.268 |
| Part 1: EU RPP | Absolute PASI Score at Baseline | 20.29 units on a scale | Standard Deviation 8.266 |
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.
Time frame: Week 16
Population: PP Analysis Set. Only those participants contributing data at Week 16 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: M923 | Absolute PASI Score at Week 16 | 2.58 units on a scale | Standard Deviation 4.092 |
| Part 1: EU RPP | Absolute PASI Score at Week 16 | 2.50 units on a scale | Standard Deviation 3.098 |
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.
Time frame: Week 52
Population: PP Analysis Set. Only those participants contributing data at Week 52 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: M923 | Absolute PASI Score at Week 52 (Follow-Up Visit) | 2.76 units on a scale | Standard Deviation 4.768 |
| Part 1: EU RPP | Absolute PASI Score at Week 52 (Follow-Up Visit) | 2.85 units on a scale | Standard Deviation 4.913 |
| Part 2: Continuous EU RPP | Absolute PASI Score at Week 52 (Follow-Up Visit) | 2.67 units on a scale | Standard Deviation 3.919 |
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.
Time frame: Baseline
Population: Analysis was performed using PP Analysis Set including participants with evaluable data for part 1 and part 2 of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: M923 | Health-Related Quality of Life During Treatment: Dermatology Life Quality Index (DLQI) Score at Baseline | 12.5 units on a scale | Standard Deviation 7.13 |
| Part 1: EU RPP | Health-Related Quality of Life During Treatment: Dermatology Life Quality Index (DLQI) Score at Baseline | 10.5 units on a scale | Standard Deviation 6.71 |
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.
Time frame: Week 16
Population: PP Analysis Set. Only those participants contributing data at Week 16 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: M923 | Health-Related Quality of Life During Treatment: DLQI Score at Week 16 | 2.4 units on a scale | Standard Deviation 4.04 |
| Part 1: EU RPP | Health-Related Quality of Life During Treatment: DLQI Score at Week 16 | 2.1 units on a scale | Standard Deviation 3.5 |
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.
Time frame: Week 48
Population: PP Analysis Set. Only those participants contributing data at Week 48 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: M923 | Health-Related Quality of Life During Treatment: DLQI Score at Week 48 (Completion/Termination Visit) | 2.1 units on a scale | Standard Deviation 3.77 |
| Part 1: EU RPP | Health-Related Quality of Life During Treatment: DLQI Score at Week 48 (Completion/Termination Visit) | 1.6 units on a scale | Standard Deviation 2.83 |
| Part 2: Continuous EU RPP | Health-Related Quality of Life During Treatment: DLQI Score at Week 48 (Completion/Termination Visit) | 2.1 units on a scale | Standard Deviation 3.97 |
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.
Time frame: Week 16
Population: PP Analysis Set. Only those participants contributing data at Week 16 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: M923 | Health-Related Quality of Life During Treatment: EQ-5D-5L at Week 16 | 83.7 units on a scale | Standard Deviation 12.38 |
| Part 1: EU RPP | Health-Related Quality of Life During Treatment: EQ-5D-5L at Week 16 | 83.4 units on a scale | Standard Deviation 13.92 |
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.
Time frame: Week 48
Population: PP Analysis Set. Only those participants contributing data at Week 48 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: M923 | Health-Related Quality of Life During Treatment: EQ-5D-5L at Week 48 (Completion/Termination Visit) | 85.3 units on a scale | Standard Deviation 13.83 |
| Part 1: EU RPP | Health-Related Quality of Life During Treatment: EQ-5D-5L at Week 48 (Completion/Termination Visit) | 83.9 units on a scale | Standard Deviation 14.92 |
| Part 2: Continuous EU RPP | Health-Related Quality of Life During Treatment: EQ-5D-5L at Week 48 (Completion/Termination Visit) | 84.2 units on a scale | Standard Deviation 12.98 |
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.
Time frame: Baseline
Population: Analysis was performed using PP Analysis Set including participants with evaluable data for part 1 and part 2 of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: M923 | Health-Related Quality of Life During Treatment: EuroQoL 5-Dimension Health Status Questionnaire (EQ-5D-5L) at Baseline | 71.3 units on a scale | Standard Deviation 18.7 |
| Part 1: EU RPP | Health-Related Quality of Life During Treatment: EuroQoL 5-Dimension Health Status Questionnaire (EQ-5D-5L) at Baseline | 72.5 units on a scale | Standard Deviation 20.27 |
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.
Time frame: Baseline (Week 0)
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Baseline | No positive result | 266 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Baseline | Predose positive result | 16 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Baseline | No positive result | 271 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Baseline | Predose positive result | 13 Participants |
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.
Time frame: Week 16
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 16 | Titers ≤ 1:16 (postdose positive ADAs) | 16 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 16 | Titers ≤ 1:16 (postdose positive nADAs) | 2 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 16 | Titers > 1:16 to ≤ 1:128 (postdose positive ADAs) | 90 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 16 | Titers > 1:16 to ≤ 1:128 (postdose positive nADAs) | 17 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 16 | Titers >1:128 to ≤ 1:152 (postdose positive ADAs) | 27 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 16 | Titers >1:128 to ≤ 1:152 (postdose positive nADAs) | 3 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 16 | Titers >1:152 (postdose positive ADAs) | 6 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 16 | Titers >1:152 (postdose positive nADAs) | 6 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 16 | Titers >1:152 (postdose positive nADAs) | 11 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 16 | Titers ≤ 1:16 (postdose positive ADAs) | 26 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 16 | Titers >1:128 to ≤ 1:152 (postdose positive ADAs) | 40 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 16 | Titers ≤ 1:16 (postdose positive nADAs) | 2 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 16 | Titers >1:152 (postdose positive ADAs) | 13 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 16 | Titers > 1:16 to ≤ 1:128 (postdose positive ADAs) | 73 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 16 | Titers >1:128 to ≤ 1:152 (postdose positive nADAs) | 11 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 16 | Titers > 1:16 to ≤ 1:128 (postdose positive nADAs) | 6 Participants |
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.
Time frame: Week 25
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers ≤ 1:16 (postdose positive ADAs) | 24 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers ≤ 1:16 (postdose positive nADAs) | 6 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers > 1:16 to ≤ 1:128 (postdose positive ADAs) | 86 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers > 1:16 to ≤ 1:128 (postdose positive nADAs) | 17 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers >1:128 to ≤ 1:152 (postdose positive ADAs) | 28 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers >1:128 to ≤ 1:152 (postdose positive nADAs) | 16 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers >1:152 (postdose positive ADAs) | 18 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers >1:152 (postdose positive nADAs) | 16 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers > 1:16 to ≤ 1:128 (postdose positive ADAs) | 37 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers >1:152 (postdose positive ADAs) | 15 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers > 1:16 to ≤ 1:128 (postdose positive nADAs) | 4 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers >1:128 to ≤ 1:152 (postdose positive ADAs) | 14 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers >1:128 to ≤ 1:152 (postdose positive nADAs) | 6 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers ≤ 1:16 (postdose positive ADAs) | 19 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers ≤ 1:16 (postdose positive nADAs) | 2 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers >1:152 (postdose positive nADAs) | 13 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers > 1:16 to ≤ 1:128 (postdose positive ADAs) | 42 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers ≤ 1:16 (postdose positive nADAs) | 4 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers ≤ 1:16 (postdose positive ADAs) | 21 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers > 1:16 to ≤ 1:128 (postdose positive nADAs) | 7 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers >1:152 (postdose positive ADAs) | 12 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers >1:128 to ≤ 1:152 (postdose positive nADAs) | 10 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers >1:128 to ≤ 1:152 (postdose positive ADAs) | 22 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 25 | Titers >1:152 (postdose positive nADAs) | 11 Participants |
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.
Time frame: Week 52
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers ≤ 1:16 (postdose positive ADAs) | 26 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers ≤ 1:16 (postdose positive nADAs) | 0 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers > 1:16 to ≤ 1:128 (postdose positive ADAs) | 62 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers > 1:16 to ≤ 1:128 (postdose positive nADAs) | 13 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers >1:128 to ≤ 1:152 (postdose positive ADAs) | 23 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers >1:128 to ≤ 1:152 (postdose positive nADAs) | 9 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers >1:152 (postdose positive ADAs) | 13 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers >1:152 (postdose positive nADAs) | 11 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers > 1:16 to ≤ 1:128 (postdose positive ADAs) | 37 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers >1:152 (postdose positive ADAs) | 7 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers > 1:16 to ≤ 1:128 (postdose positive nADAs) | 6 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers >1:128 to ≤ 1:152 (postdose positive ADAs) | 12 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers >1:128 to ≤ 1:152 (postdose positive nADAs) | 6 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers ≤ 1:16 (postdose positive ADAs) | 11 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers ≤ 1:16 (postdose positive nADAs) | 2 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers >1:152 (postdose positive nADAs) | 6 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers > 1:16 to ≤ 1:128 (postdose positive ADAs) | 38 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers ≤ 1:16 (postdose positive nADAs) | 3 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers ≤ 1:16 (postdose positive ADAs) | 17 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers > 1:16 to ≤ 1:128 (postdose positive nADAs) | 5 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers >1:152 (postdose positive ADAs) | 10 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers >1:128 to ≤ 1:152 (postdose positive nADAs) | 2 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers >1:128 to ≤ 1:152 (postdose positive ADAs) | 15 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA and nADA by Titer at Week 52 (Completion/Termination Visit) | Titers >1:152 (postdose positive nADAs) | 7 Participants |
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.
Time frame: Week 16
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: M923 | Immunogenicity: Number of Participants With ADA at Week 16 | EU Humera | 135 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA at Week 16 | M923 | 4 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA at Week 16 | Overall Results | 139 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA at Week 16 | Neutralizing ADA | 28 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA at Week 16 | Neutralizing ADA | 30 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA at Week 16 | EU Humera | 144 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA at Week 16 | Overall Results | 152 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA at Week 16 | M923 | 8 Participants |
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.
Time frame: Week 25
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: M923 | Immunogenicity: Number of Participants With ADA at Week 25 | EU Humera | 144 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA at Week 25 | M923 | 12 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA at Week 25 | Overall result | 156 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA at Week 25 | Neutralizing ADA | 55 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA at Week 25 | Neutralizing ADA | 25 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA at Week 25 | EU Humera | 80 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA at Week 25 | Overall result | 85 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA at Week 25 | M923 | 5 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA at Week 25 | Neutralizing ADA | 32 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA at Week 25 | M923 | 5 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA at Week 25 | Overall result | 97 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA at Week 25 | EU Humera | 92 Participants |
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.
Time frame: Week 52
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: M923 | Immunogenicity: Number of Participants With ADA at Week 52 (Completion/Termination Visit) | EU Humera | 131 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA at Week 52 (Completion/Termination Visit) | M923 | 10 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA at Week 52 (Completion/Termination Visit) | Overall result | 141 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With ADA at Week 52 (Completion/Termination Visit) | Neutralizing ADA | 40 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA at Week 52 (Completion/Termination Visit) | Neutralizing ADA | 28 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA at Week 52 (Completion/Termination Visit) | EU Humera | 73 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA at Week 52 (Completion/Termination Visit) | Overall result | 79 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With ADA at Week 52 (Completion/Termination Visit) | M923 | 6 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA at Week 52 (Completion/Termination Visit) | Neutralizing ADA | 23 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA at Week 52 (Completion/Termination Visit) | M923 | 7 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA at Week 52 (Completion/Termination Visit) | Overall result | 87 Participants |
| Part 2: Continuous EU RPP | Immunogenicity: Number of Participants With ADA at Week 52 (Completion/Termination Visit) | EU Humera | 80 Participants |
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.
Time frame: Baseline (Week 0)
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: M923 | Immunogenicity: Number of Participants With Anti-Drug Antibodies (ADA) at Baseline | EU Humera | 15 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With Anti-Drug Antibodies (ADA) at Baseline | M923 | 1 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With Anti-Drug Antibodies (ADA) at Baseline | Overall Results | 16 Participants |
| Part 1: M923 | Immunogenicity: Number of Participants With Anti-Drug Antibodies (ADA) at Baseline | Neutralizing ADA | 4 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With Anti-Drug Antibodies (ADA) at Baseline | Neutralizing ADA | 2 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With Anti-Drug Antibodies (ADA) at Baseline | EU Humera | 11 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With Anti-Drug Antibodies (ADA) at Baseline | Overall Results | 13 Participants |
| Part 1: EU RPP | Immunogenicity: Number of Participants With Anti-Drug Antibodies (ADA) at Baseline | M923 | 2 Participants |
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.
Time frame: Up to Week 52
Population: Safety Analysis Set. Only those participants who had a postdose seroconversion time were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: M923 | Median Time to Seroconversion | 113.0 days |
| Part 1: EU RPP | Median Time to Seroconversion | 113.0 days |
| Part 2: Continuous EU RPP | Median Time to Seroconversion | 112.0 days |
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.
Time frame: Baseline; Week 16
Population: PP Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: M923 | Number of Participants Achieving PASI 50 Response at Week 16 | 243 Participants |
| Part 1: EU RPP | Number of Participants Achieving PASI 50 Response at Week 16 | 253 Participants |
90% CI: [-0.061, 0.016]
95% CI: [-0.069, 0.024]
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.
Time frame: Baseline; Week 52
Population: PP Analysis Set. Only those participants contributing data at Week 52 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: M923 | Number of Participants Achieving PASI 50 Response at Week 52 (Follow-Up Visit) | 228 Participants |
| Part 1: EU RPP | Number of Participants Achieving PASI 50 Response at Week 52 (Follow-Up Visit) | 111 Participants |
| Part 2: Continuous EU RPP | Number of Participants Achieving PASI 50 Response at Week 52 (Follow-Up Visit) | 113 Participants |
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.
Time frame: Baseline; Week 52
Population: PP Analysis Set. Only those participants contributing data at Week 52 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: M923 | Number of Participants Achieving PASI 75 Response at Week 52 (Follow-Up Visit) | 202 Participants |
| Part 1: EU RPP | Number of Participants Achieving PASI 75 Response at Week 52 (Follow-Up Visit) | 96 Participants |
| Part 2: Continuous EU RPP | Number of Participants Achieving PASI 75 Response at Week 52 (Follow-Up Visit) | 101 Participants |
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.
Time frame: Baseline; Week 16
Population: PP Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: M923 | Number of Participants Achieving PASI 90 Response at Week 16 | 165 Participants |
| Part 1: EU RPP | Number of Participants Achieving PASI 90 Response at Week 16 | 147 Participants |
90% CI: [0.01, 0.149]
95% CI: [-0.004, 0.162]
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.
Time frame: Baseline; Week 52
Population: PP Analysis Set. Only those participants contributing data at Week 52 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: M923 | Number of Participants Achieving PASI 90 Response at Week 52 (Follow-Up Visit) | 159 Participants |
| Part 1: EU RPP | Number of Participants Achieving PASI 90 Response at Week 52 (Follow-Up Visit) | 71 Participants |
| Part 2: Continuous EU RPP | Number of Participants Achieving PASI 90 Response at Week 52 (Follow-Up Visit) | 77 Participants |
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.
Time frame: Up to Week 52
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: M923 | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 Participants |
| Part 2: Transition EU RPP | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Meaningful Changes in Vital Signs | 0 Participants |
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.
Time frame: Baseline
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram Parameters at Baseline | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram Parameters at Baseline | 0 Participants |
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.
Time frame: Week 16
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram Parameters at Week 16 | 2 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram Parameters at Week 16 | 0 Participants |
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.
Time frame: Week 48
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram Parameters at Week 48 (Completion/Termination Visit) | 3 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram Parameters at Week 48 (Completion/Termination Visit) | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram Parameters at Week 48 (Completion/Termination Visit) | 0 Participants |
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.
Time frame: Baseline
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Lymphocytes absolute | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Gamma glutamyl transferase | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | White blood cell count (total leucocytes) | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Creatine kinase | 2 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Lymphocytes | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | C-reactive protein | 6 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Hematocrit | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Cholesterol | 2 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Monocytes | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Triglycerides | 3 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Neutrophils absolute | 2 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Total protein | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Eosinophils absolute | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Potassium | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Mean cell volume | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Urea | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Eosinophils | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Creatinine | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Neutrophils | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Phosphate | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Aspartate transaminase | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Glucose | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Platelet count | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Uric acid | 2 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Alanine transaminase | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Specific Gravity | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Hemoglobin | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Specific Gravity | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Hemoglobin | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Hematocrit | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Platelet count | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Mean cell volume | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | White blood cell count (total leucocytes) | 1 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Neutrophils absolute | 1 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Neutrophils | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Lymphocytes absolute | 1 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Lymphocytes | 1 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Monocytes | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Eosinophils absolute | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Eosinophils | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Aspartate transaminase | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Alanine transaminase | 1 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Gamma glutamyl transferase | 4 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Creatine kinase | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | C-reactive protein | 2 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Cholesterol | 4 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Triglycerides | 2 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Total protein | 1 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Potassium | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Urea | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Creatinine | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Phosphate | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Glucose | 2 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Baseline | Uric acid | 0 Participants |
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.
Time frame: Week 16
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Uric acid | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Neutrophils absolute | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Creatinine | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Neutrophils | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Specific Gravity | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Lymphocytes absolute | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Total protein | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Lymphocytes | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Hemoglobin | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Monocytes | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Phosphate | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Eosinophils absolute | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Hematocrit | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Eosinophils | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Urea | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Aspartate transaminase | 2 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Platelet count | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Alanine transaminase | 3 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Glucose | 2 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Gamma glutamyl transferase | 3 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Mean cell volume | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Creatine kinase | 2 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Potassium | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | C-reactive protein | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | White blood cell count (total leucocytes) | 2 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Cholesterol | 4 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Triglycerides | 5 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Cholesterol | 3 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Triglycerides | 3 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Total protein | 1 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Potassium | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Urea | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Creatinine | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Phosphate | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Glucose | 3 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Uric acid | 1 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Specific Gravity | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Hemoglobin | 1 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Hematocrit | 1 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Platelet count | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Mean cell volume | 1 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | White blood cell count (total leucocytes) | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Neutrophils absolute | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Neutrophils | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Lymphocytes absolute | 1 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Lymphocytes | 1 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Monocytes | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Eosinophils absolute | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Eosinophils | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Aspartate transaminase | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Alanine transaminase | 1 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Gamma glutamyl transferase | 2 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | Creatine kinase | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 16 | C-reactive protein | 0 Participants |
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.
Time frame: Week 48
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Hemoglobin | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Triglycerides | 11 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Eosinophils absolute | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Glucose | 5 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Cholesterol | 7 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Eosinophils | 2 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Mean cell volume | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | C-reactive protein | 3 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Aspartate transaminase | 2 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Red Blood Cell Count | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Creatine kinase | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Alanine transaminase | 5 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Phosphate | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Total bilirubin | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Alkaline Phosphatase | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | White blood cell count (total leucocytes) | 2 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Gamma glutamyl transferase | 3 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | pH | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Albumin | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Neutrophils absolute | 3 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Hematocrit | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Creatinine | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Neutrophils | 3 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Specific Gravity | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Urea | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Lymphocytes absolute | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Chloride | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Potassium | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Lymphocytes | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Uric acid | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Sodium | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Monocytes absolute | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Platelet count | 1 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Total protein | 0 Participants |
| Part 1: M923 | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Monocytes | 1 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Lymphocytes absolute | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Red Blood Cell Count | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Hemoglobin | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Hematocrit | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Platelet count | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Mean cell volume | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | White blood cell count (total leucocytes) | 1 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Neutrophils absolute | 1 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Neutrophils | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Lymphocytes | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Monocytes absolute | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Monocytes | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Eosinophils absolute | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Eosinophils | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Aspartate transaminase | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Alanine transaminase | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Alkaline Phosphatase | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Gamma glutamyl transferase | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Total bilirubin | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Creatine kinase | 1 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | C-reactive protein | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Cholesterol | 3 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Triglycerides | 4 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Total protein | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Sodium | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Potassium | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Chloride | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Urea | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Creatinine | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Albumin | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Phosphate | 0 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Glucose | 3 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Uric acid | 3 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | pH | 1 Participants |
| Part 1: EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Specific Gravity | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Monocytes absolute | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Phosphate | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Total protein | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Lymphocytes | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Platelet count | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Sodium | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Lymphocytes absolute | 1 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Specific Gravity | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Potassium | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | pH | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Glucose | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Chloride | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Neutrophils | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Hematocrit | 1 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Urea | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Neutrophils absolute | 2 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Red Blood Cell Count | 1 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Alkaline Phosphatase | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Creatinine | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Gamma glutamyl transferase | 3 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Alanine transaminase | 3 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | White blood cell count (total leucocytes) | 1 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Total bilirubin | 1 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Aspartate transaminase | 1 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Uric acid | 3 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Creatine kinase | 1 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Eosinophils | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Albumin | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | C-reactive protein | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Eosinophils absolute | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Mean cell volume | 1 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Cholesterol | 2 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Monocytes | 0 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Hemoglobin | 1 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters at Week 48 (Completion/Termination Visit) | Triglycerides | 2 Participants |
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.
Time frame: Up to Week 52
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: M923 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 169 Participants |
| Part 1: EU RPP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 194 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 199 Participants |
| Part 2: Transition EU RPP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 99 Participants |
| Part 2: Continuous EU RPP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 103 Participants |
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.
Time frame: Week 16
Population: PP Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: M923 | Percentage of Participants With a Response of Clear or Almost Clear on the Static Physician Global Assessment (sPGA) at Week 16 | 68.9 percentage of participants |
| Part 1: EU RPP | Percentage of Participants With a Response of Clear or Almost Clear on the Static Physician Global Assessment (sPGA) at Week 16 | 66.1 percentage of participants |
95% CI: [-0.048, 0.11]
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.
Time frame: Baseline; Week 16
Population: PP Analysis Set. Only those participants contributing data at Week 16 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: M923 | Percent Change From Baseline in PASI Score at Week 16 | -86.21 percent change | Standard Deviation 20.065 |
| Part 1: EU RPP | Percent Change From Baseline in PASI Score at Week 16 | -86.79 percent change | Standard Deviation 15.756 |
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.
Time frame: Baseline; Week 52
Population: PP Analysis Set. Only those participants contributing data at Week 52 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: M923 | Percent Change From Baseline in PASI Score at Week 52 (Follow-Up Visit) | -86.43 percent change | Standard Deviation 22.57 |
| Part 1: EU RPP | Percent Change From Baseline in PASI Score at Week 52 (Follow-Up Visit) | -85.53 percent change | Standard Deviation 21.771 |
| Part 2: Continuous EU RPP | Percent Change From Baseline in PASI Score at Week 52 (Follow-Up Visit) | -85.64 percent change | Standard Deviation 20.968 |
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).
Time frame: Baseline (Week 0), Week 8, 16, 17, 21, 25, 29, 37, and 41
Population: Pharmacokinetic (PK) Analysis Set: all participants who received at least 1 dose of study drug and had at least 1 measured concentration at a scheduled PK time point after start of dosing. Only participants with evaluable data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: M923 | Pharmacokinetics: Serum Concentrations by Treatment | Baseline (Week 0)/Predose | 302 nanograms per milliter (ng/mL) | Standard Deviation 16.5 |
| Part 1: M923 | Pharmacokinetics: Serum Concentrations by Treatment | Week 16/Peak | 8580 nanograms per milliter (ng/mL) | Standard Deviation 5700 |
| Part 1: M923 | Pharmacokinetics: Serum Concentrations by Treatment | Week 8/Peak | 9100 nanograms per milliter (ng/mL) | Standard Deviation 5450 |
| Part 1: EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Baseline (Week 0)/Predose | 301 nanograms per milliter (ng/mL) | Standard Deviation 9.69 |
| Part 1: EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 8/Peak | 7640 nanograms per milliter (ng/mL) | Standard Deviation 4370 |
| Part 1: EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 16/Peak | 6990 nanograms per milliter (ng/mL) | Standard Deviation 5100 |
| Part 2: Continuous EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 25/Trough | 6790 nanograms per milliter (ng/mL) | Standard Deviation 5210 |
| Part 2: Continuous EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 21/Trough | 6630 nanograms per milliter (ng/mL) | Standard Deviation 4960 |
| Part 2: Continuous EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 37/Trough | 6120 nanograms per milliter (ng/mL) | Standard Deviation 4220 |
| Part 2: Continuous EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 17/Trough | 6900 nanograms per milliter (ng/mL) | Standard Deviation 5270 |
| Part 2: Continuous EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 41/Trough | 5950 nanograms per milliter (ng/mL) | Standard Deviation 4230 |
| Part 2: Continuous EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 29/Trough | 5990 nanograms per milliter (ng/mL) | Standard Deviation 4020 |
| Part 2: Transition EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 17/Trough | 5840 nanograms per milliter (ng/mL) | Standard Deviation 4840 |
| Part 2: Transition EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 37/Trough | 5250 nanograms per milliter (ng/mL) | Standard Deviation 4190 |
| Part 2: Transition EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 25/Trough | 6320 nanograms per milliter (ng/mL) | Standard Deviation 5260 |
| Part 2: Transition EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 21/Trough | 6260 nanograms per milliter (ng/mL) | Standard Deviation 4960 |
| Part 2: Transition EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 29/Trough | 5330 nanograms per milliter (ng/mL) | Standard Deviation 4000 |
| Part 2: Transition EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 41/Trough | 5480 nanograms per milliter (ng/mL) | Standard Deviation 4140 |
| Part 2: Continuous EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 21/Trough | 5100 nanograms per milliter (ng/mL) | Standard Deviation 4040 |
| Part 2: Continuous EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 25/Trough | 4970 nanograms per milliter (ng/mL) | Standard Deviation 3870 |
| Part 2: Continuous EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 29/Trough | 4840 nanograms per milliter (ng/mL) | Standard Deviation 3480 |
| Part 2: Continuous EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 37/Trough | 4830 nanograms per milliter (ng/mL) | Standard Deviation 3680 |
| Part 2: Continuous EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 41/Trough | 4740 nanograms per milliter (ng/mL) | Standard Deviation 3710 |
| Part 2: Continuous EU RPP | Pharmacokinetics: Serum Concentrations by Treatment | Week 17/Trough | 5340 nanograms per milliter (ng/mL) | Standard Deviation 4050 |