Efficacy and Safety Study of SUNPG1623

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, multiple-dose, phase 2b study to demonstrate the safety and efficacy of SUNPG1623

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose, Phase 2b Study to Demonstrate the Safety and Efficacy of Tildrakizumab in Subjects With Active Psoriatic Arthritis

Conditions
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Active Psoriatic Arthritis

Intervention / Treatment
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* Drug: SUNPG1623 I
* Drug: SUNPG1623 II
* Drug: SUNPG1623 III
* Drug: SUNPG1623 IV
* Drug: PLACEBO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has provided written informed consent Subject is ≥ 18 years of age at time of Screening Subject must be on stable dose of NSAID for ≥ 4 weeks prior to initiation of IMP Subject has a negative evaluation for TB within 4 weeks before initiating IMP Subject has a diagnosis of PsA (by the Classification of Psoriatic Arthritis [CASPAR] criteria) with symptoms present for at least 6 months. Subject has ≥ 3 tender and ≥ 3 swollen joints at Screening and Baseline. Exclusion Criteria: Subject has a planned surgical intervention between Baseline and the Week 24 evaluation for a pretreatment condition Subject has an active infection or history of infections Subject has any concurrent medical condition or uncontrolled, clinically significant systemic disease Subject has a known history of infection with hepatitis B, hepatitis C, or human immunodeficiency virus

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SUNPG1623 dose I<br>low range dose | Drug: SUNPG1623 I<br>* injection<br>|
| Experimental: SUNPG1623 dose II<br>mid range dose | Drug: SUNPG1623 II<br>* injection<br>Drug: PLACEBO<br>* injection<br>|
| Experimental: SUNPG1623 dose III<br>mid range dose | Drug: SUNPG1623 III<br>* injection<br>Drug: PLACEBO<br>* injection<br>|
| Experimental: SUNPG1623 dose IV<br>mid range dose to high dose | Drug: SUNPG1623 IV<br>* injection<br>Drug: PLACEBO<br>* injection<br>|
| Placebo Comparator: Placebo<br>mid range dose to high dose | Drug: PLACEBO<br>* injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Who Achieve American College of Rheumatology20 Response Rate | The American College of Rheumatology20 response measured the percentage of subjects with at least a 20% improvement from Baseline in both tender joints (68) and swollen joints (66) and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, patient pain assessment, patient self-assessed disability, and acute-phase C-reactive protein. For 'Units of Measure'- Data entered is proportion of participants, which is calculated by dividing the value obtained (percentage in this case) by 100. | week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Achieving American College of Rheumatology70 Response Rate | The American College of Rheumatology70 response measured the percentage of subjects with at least a 50% improvement from Baseline in both tender joints (68) and swollen joints (66) and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, patient pain assessment, patient self-assessed disability, and acute-phase C-reactive protein. For 'Units of Measure'- Data entered is proportion of participants, which is calculated by dividing the value obtained (percentage in this case) by 100. | week 1, week 4, week 8, week 12, week 16, week 20, week 24, and week 52 | 
| Change From Baseline in Tender Joint Counts | Peripheral joints were assessed for tenderness and swelling. There is no validated measure to assess peripheral joints in Psoriatic arthritis; the measure used was the American College of Rheumatology joint count initially developed for the assessment of patients with rheumatoid arthritis. | week 1, week 4, week 8, week 12, week 16, week 20, and week 24 | 
| Change From Baseline in Tender Joint Counts | Peripheral joints were assessed for tenderness and swelling. There is no validated measure to assess peripheral joints in Psoriatic arthritis; the measure used was the American College of Rheumatology joint count initially developed for the assessment of patients with rheumatoid arthritis. | Week 52 | 
| Change From Baseline in Swollen Joint Counts | Peripheral joints were assessed for tenderness and swelling. There is no validated measure to assess peripheral joints in Psoriatic arthritis; the measure used was the American College of Rheumatology joint count initially developed for the assessment of patients with rheumatoid arthritis. | week 1, week 4, week 8, week 12, week 16, week 20, and week 24 | 
| Change From Baseline in Swollen Joint Counts | Peripheral joints were assessed for tenderness and swelling. There is no validated measure to assess peripheral joints in Psoriatic arthritis; the measure used was the American College of Rheumatology joint count initially developed for the assessment of patients with rheumatoid arthritis. | Week 52 | 
| Physician Global Assessment of Disease Activity Visual Analog Scale | 100 mm Visual analog scale with descriptors (verbal) : very good (0) to very poor (100) | week 1, week 4, week 8, week 12, week 16, week 20, and week 24 | 
| Change From Baseline in Physician Global Assessment of Disease Activity Visual Analog Scale | 100 mm Visual analog scale with descriptors (verbal) : very good (0) to very poor (100) | Week 52 | 
| Patient's Global Assessment of Disease Activity | 100 mm Visual analog scale descriptors (verbal) : very well (0) to very poorly(100) | week 1, week 4, week 8, week 12, week 16, week 20 and week 24 | 
| Change From Baseline in Patient's Global Assessment of Disease Activity | 100 mm Visual analog scale descriptors (verbal) : very well (0) to very poorly(100) | Week 52 | 
| Patient's Pain Assessment | 100 mm Visual Analog Scale with scale (verbal descriptors) no pain (0) to worst possible pain (100). | week 1, week 4, week 8, week 12, week 16, week 20, and week 24 | 
| Change From Baseline in Patient's Pain Assessment | 100 mm Visual Analog Scale with scale (verbal descriptors) no pain (0) to worst possible pain (100). | Week 52 | 
| Health Assessment Questionnaire- Disability Index | eight categories assessed by the Health Assessment Questionnaire - Disability Index 1) dressing and grooming, 2) arising, 3) eating, 4) walking, 5) hygiene, 6) reach, 7) grip and 8) common daily activities was scored as 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty) or 3 (unable to do). The score for the disability index is the mean of the 8 category scores. If more than 2 of the categories, or 25%, are missing, the scale is not scored. If fewer than 2 of the categories are missing, the sum of the categories is divided by the number of answered categories. A higher score indicates greater disability | week 1, week 4, week 8, week 12, week 16, week 20, and week 24 | 
| Proportion of Subjects Who Achieve American College of Rheumatology20 Response Rate | The American College of Rheumatology20 response measured the percentage of subjects with at least a 20% improvement from Baseline in both tender joints (68) and swollen joints (66) and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, patient pain assessment, patient self-assessed disability, and acute-phase C-reactive protein. For 'Units of Measure'- Data entered is proportion of participants, which is calculated by dividing the value obtained (percentage in this case) by 100. | week 52 | 
| Proportion of Subjects Achieving American College of Rheumatology50 Response Rate | The American College of Rheumatology50 response measured the percentage of subjects with at least a 50% improvement from Baseline in both tender joints (68) and swollen joints (66) and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, patient pain assessment, patient self-assessed disability, and acute-phase C-reactive protein. For 'Units of Measure'- Data entered is proportion of participants, which is calculated by dividing the value obtained (percentage in this case) by 100. | week 1, week 4, week 8, week 12, week 16, week 20, week 24 and week 52 | 
| Change From Baseline in Health Assessment Questionnaire- Disability Index | eight categories assessed by the Health Assessment Questionnaire - Disability Index 1) dressing and grooming, 2) arising, 3) eating, 4) walking, 5) hygiene, 6) reach, 7) grip and 8) common daily activities was scored as 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty) or 3 (unable to do). The score for the disability index is the mean of the 8 category scores. If more than 2 of the categories, or 25%, are missing, the scale is not scored. If fewer than 2 of the categories are missing, the sum of the categories is divided by the number of answered categories. A higher score indicates greater disability | Week 52 | 
| Acute Phase C - Reactive Protein | C-reactive protein (CRP) is a blood test marker for inflammation in the body. CRP is produced in the liver and its level is measured by testing the blood. CRP is classified as an acute phase reactant, which means that its levels will rise in response to inflammation | week 1, week 4, week 8, week 12, week 16, week 20, and week 24 | 
| Acute Phase C - Reactive Protein | C-reactive protein (CRP) is a blood test marker for inflammation in the body. CRP is produced in the liver and its level is measured by testing the blood. CRP is classified as an acute phase reactant, which means that its levels will rise in response to inflammation. Change from Baseline in C-Reactive Protein. | Week 52 | 
| Erythrocyte Sedimentation Rate | An erythrocyte sedimentation rate (ESR) is a type of blood test that measures how quickly erythrocytes (red blood cells) settle at the bottom of a test tube that contains a blood sample. This test help determine if you have a condition that causes inflammation. | week 1, week 4, week 8, week 12, week 16, week 20, and week 24 | 
| Change From Baseline in Erythrocyte Sedimentation Rate | An erythrocyte sedimentation rate (ESR) is a type of blood test that measures how quickly erythrocytes (red blood cells) settle at the bottom of a test tube that contains a blood sample. This test help determine if you have a condition that causes inflammation. | Week 52 | 
| The Proportion of Subjects Who Require Adjustment of Background Therapy |  | Week 16 | 
| Disease Activity Score (DAS) 28 (Joints) C - Reactive Protein (DAS28-CRP) Response Rate | The Disease Activity Score 28-item C-Reactive Protein: assessed across 28 joints including the shoulder, elbow, wrist, MCP (1 through 5), PIP (1 through 5) and knee, with all 14 joints assessed for each side of the body. It is a composite score derived from examination of the 28 joints for swelling and tenderness, global assessment of pain and overall status using a VAS and a blood marker of inflammation (hsCRP). DAS28-CRP(4) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.014*GH + 0.96 TJC- tender joint count, SJC- swollen joint count, CRP- C reactive protein, GH - patient global health | week 1, week 4, week 8, week 12, week 16, week 20, week 24 and Week 52 | 
| Minimal Disease Activity | A psoriatic arthritis patient is defined as having a Minimal Disease Activity (MDA) response (Yes/No) when the patient meets at least 5 of the 7 following criteria: tender joint count ≤1; swollen joint count ≤1; PASI score ≤1 or BSA ≤3%; patient Arthritis Pain (VAS) ≤15 mm; patient's global arthritis assessment (VAS) ≤20 mm; HAQ-DI score ≤0.5; tender entheseal points (using LEI) ≤1. | week 1, week 4, week 8, week 12, week 16, week 20, week 24 and week 52 | 
| Change From Baseline in Leeds Dactylitis Index (LDI) | tenderness score (0 = no tenderness, 1 = tender, 2 = tender and wince, and 3 = tender and withdraw) Total score= {[Circumference involved digit/ Circumference contralateral Digit (or Tables)] - 1x 100}x Tenderness score Standard reference: Hands Digit Men Women Thumb 70 58 Index 63 54 Middle 63 54 Ring 59 50 Little 52 44 Standard reference: Feet Digit Men Women Great Toe 82 72 Second 52 46 Middle 50 44 Fourth 50 44 Little 52 45 The difference between circumference of affected finger and contralateral not affected digit cannot be defined for maximum value. Therefore, it is difficult to provide scale range for the final score. No theoretical range exists for the Leeds Dactylitis Index. Lower Leeds Dactylitis Index score represent better outcome. | week 4, week 12, and week 24 | 
| Change From Baseline in Leeds Dactylitis Index (LDI) | tenderness score (0 = no tenderness, 1 = tender, 2 = tender and wince, and 3 = tender and withdraw) Total score= {[Circumference involved digit/ Circumference contralateral Digit (or Tables)] - 1x 100}x Tenderness score Standard reference: Hands Digit Men Women Thumb 70 58 Index 63 54 Middle 63 54 Ring 59 50 Little 52 44 Standard reference: Feet Digit Men Women Great Toe 82 72 Second 52 46 Middle 50 44 Fourth 50 44 Little 52 45 The difference between circumference of affected finger and contralateral not affected digit cannot be defined for maximum value. Therefore, it is difficult to provide scale range for the final score. No theoretical range exists for the Leeds Dactylitis Index. Lower Leeds Dactylitis Index score represent better outcome. | Week 52 | 
| Change From Baseline in Leeds Enthesitis Index (LEI) | The LEI examines tenderness at 6 sites: 2 sites (left and right) at each of the lateral epicondyles of the humerus, medial condyles of the femur and the insertion of the Achilles tendon. For each entheseal site, assessment is made of the adjacent joint in terms of tenderness and soft-tissue swelling, with a score of 1 if present. The LEI score range is 0-6. Lower the score better is the outcome | week 4, week 12 and week 24 | 
| Change From Baseline in Leeds Enthesitis Index (LEI) | The LEI examines tenderness at 6 sites: 2 sites (left and right) at each of the lateral epicondyles of the humerus, medial condyles of the femur and the insertion of the Achilles tendon. For each entheseal site, assessment is made of the adjacent joint in terms of tenderness and soft-tissue swelling, with a score of 1 if present. The LEI score range is 0-6. Lower the score better is the outcome | Week 52 |