Efficacy and Safety of Tildrakizumab Compared to Placebo in Anti-TNF naïve Subjects With Active Psoriatic Arthritis II (INSPIRE 2)

Study Overview
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Brief Summary
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This is a randomized, double-blinded, placebo-controlled, Phase 3 study to evaluate the efficacy and safety of tildrakizumab compared to placebo in anti-TNF naïve subjects with active PsA .

Official Title
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A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Demonstrate the Efficacy and Safety of Tildrakizumab in Anti-TNF Naïve Subjects With Active Psoriatic Arthritis II (INSPIRE 2)

Conditions
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Active Psoriatic Arthritis

Intervention / Treatment
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* Drug: TILD
* Drug: matching placebo injections


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 has a diagnosis of active PsA for at least 6 months before the first administration of the study agent and has active PsA at Screening or Baseline. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP Ab) negative. Subjects must have no prior exposure to anti-tumor necrosis factor (anti-TNF) agent(s) use for the treatment of PsO or PsA. Exclusion Criteria: The subject has a planned surgical intervention between Baseline and the Week 52 evaluation for a pretreatment condition. Subject has an active infection or history of infections as follows: any active infection for which systemic anti-infectives were used within 28 days prior to first IMP dose, with the last dose having been received within 7 days of Screening, a serious infection, defined as requiring hospitalization or intravenous (IV) anti-infectives within 8 weeks prior to the first IMP dose, with the last dose having been received within 7 days of Screening, recurrent or chronic infections, e.g., chronic pyelonephritis, chronic osteomyelitis, bronchiectasis, or other active infection that, in the opinion of the Investigator, might cause this study to be detrimental to the subject. Subject has any concurrent medical condition or uncontrolled, clinically significant systemic disease (e.g., renal failure, heart failure, hypertension, liver disease, diabetes, or anemia) that, in the opinion of the Investigator, could cause this study to be detrimental to the subject. Subject has a known history of infection with hepatitis B, hepatitis C, or human immunodeficiency virus. Subject had myocardial infarction, unstable angina pectoris, or ischemic stroke within the past 6 months prior to the first IMP dose. Subject has any active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma. Subjects with a history of alcohol or drug abuse in the previous 2 years. Female subjects of childbearing potential who do not agree to abstain from heterosexual activity or practice a dual method of contraception, for example, a combination of the following: (1) oral contraceptive, depo progesterone, or intrauterine device; and (2) a barrier method (condom or diaphragm). Male subjects with female partners of childbearing potential who are not using birth control as described above must use a barrier method of contraception (e.g., condom) if not surgically sterile (i.e., vasectomy). Contraceptive methods must be practiced upon signing the Informed Consent and through 24 weeks after the last dose of IMP. If a subject discontinues prematurely, the contraceptive method must be practiced for 17 weeks following final administration of IMP. A follicle-stimulating hormone (FSH) test should be performed to confirm menopause (per reference values of the laboratory) for those women with no menses for less than 1 year. Subject currently enrolled in another investigational device/procedure or drug study, or Baseline of this study is less than 30 days or 5 half-lives (whichever is longer) since ending another investigational device/procedure or drug study(s), or receiving other investigational agent(s). Subject previously has been enrolled (randomized) in this study. Subject has any kind of disorder that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures. Donation or loss of 400 milliliter (mL) or more of blood within 8 weeks before first dose of IMP. Subjects who have been placed in an institution on official or judicial orders. Subjects who are related to or dependent on the Investigator, Sponsor, or study site such that a conflict of interest could arise.

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br> | Drug: TILD<br>* one 1 mL injection of study medication<br>|
| Placebo Comparator: Arm B<br> | Drug: matching placebo injections<br>* one 1 mL injection of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects who achieve American College of Rheumatology [ACR20] | the proportion of subjects achieving a 20% reduction from Baseline in response criteria | at Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects achieving American College of Rheumatology [ACR50] | the proportion of subjects achieving a 50% reduction from Baseline in response criteria | at Week 24 | 
| The proportion of subjects achieving American College of Rheumatology [ACR70] | the proportion of subjects achieving a 70% reduction from Baseline in response criteria | at Week 24 | 
| The proportion of subjects achieving Psoriasis Area and Severity Index 75 response among subjects with body surface area ≥3% at baseline |  | at Weeks 24 | 
| The change from Baseline in the van der Heijde modified total Sharp score |  | Week 24 | 
| The change from Baseline in the van der Heijde modified total Sharp score |  | at Week 16 | 
| The Change from Baseline in American College of Rheumatology Response Criteria Components Score | Tender Joint Count (68), Swollen Joint Count (66), Physician's Global Assessment of Arthritis (Visual Analog Scale, 0-100), Patient's Global Assessment of Arthritis (Visual Analog Scale, 0-100), Patient's Assessment of Arthritis Pain (Visual Analog Scale, 0-100), C-reactive protein levels and erythrocyte sedimentation rate levels | at Week 24 | 
| The change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index |  | at Week 24 | 
| The change from Baseline in Leeds Enthesitis Index |  | at Week 24 | 
| The change from Baseline in Leeds Dactylitis Index |  | at Week 24 | 
| The proportion of subjects who achieve a Disease Activity Score-C-reactive protein < 3.2 |  | at Week 24 | 
| The change from Baseline in van der Heijde modified Sharp sub-scores (erosion score and joint space narrowing score) |  | at Week 24 | 
| The proportion of subjects with the Change in van der Heijde modified total Sharp score <0 and < 0.5 |  | Week 24 | 
| The proportion of subjects with active Psoriasis and body surface area ≥3% | Psoriasis Area and Severity Index 90 and Psoriasis Area and Severity Index 100 | at Week 24 | 
| The change from Baseline in anti-tumor necrosis factor naïve subjects with active Psoriasis and body surface area ≥ 3% (those with involvement of nails) | Physician Global Assessment-Psoriasis and nail psoriasis severity index | at Week 24 | 
| The proportion of subjects achieving American College of Rheumatology [ACR20, ACR50 and ACR70] | the proportion of subjects achieving a 20/50/70% reduction from Baseline in response criteria | at Week 52 | 
| The change from Baseline in American College of Rheumatology Response Criteria Components Score | Tender Joint Count (68), Swollen Joint Count (66), Physician's Global Assessment of Arthritis (Visual Analog Scale, 0-100), Patient's Global Assessment of Arthritis (Visual Analog Scale, 0-100), Patient's Assessment of Arthritis Pain (Visual Analog Scale, 0-100), C-reactive protein levels and erythrocyte sedimentation rate levels | at week 52 | 
| change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index |  | at Week 52 | 
| The change from Baseline in Leeds Enthesitis Index, Leeds Dactylitis Index and Health Assessment Questionnaire Disability Index score |  | at Week 52 | 
| The proportion of subjects who achieve a Disease Activity Score(28 [joints]-C-reactive protein) < 3.2 |  | at Week 52 | 
| The change from Baseline in van der Heijde modified total Sharp score |  | at Week 52 | 
| The change from Baseline in van der Heijde modified Sharp sub-scores (erosion score and joint space narrowing score) |  | at Week 52 | 
| The proportion of subjects with the change in van der Heijde modified total Sharp score <0 and < 0.5 |  | at Week 52 | 
| In anti-tumor necrosis factor naïve subjects with active Psoriasis and body surface area ≥3%, the proportion of subjects with Psoriasis Area and Severity Index 75, Psoriasis Area and Severity Index 90 and Psoriasis Area and Severity Index 100 |  | at Week 52 | 
| In anti-tumor necrosis factor naïve subjects with active Psoriasis and body surface area ≥3% those with involvement of nails, the change from Baseline in nail psoriasis severity index |  | at Week 52 | 
| In anti-tumor necrosis factor naïve subjects with active Psoriasis and body surface area ≥3%, the change from Baseline in Physician Global Assessment-Psoriasis |  | at week 52 | 
| Change from baseline in health assessment questionnaire - disability index (HAQ-DI) score |  | at Week 24 | 
| The change from Baseline in the Short-Form-36 Health Survey Version 2 (SF-36v2), Acute Components |  | measured timepoints | 
| The change from Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scores |  | at week 24 |