Clinical trial NCT04314531: Efficacy and Safety of Tildrakizumab Compared to Placebo in Anti-TNF naïve Subjects With Active Psoriatic Arthritis II (INSPIRE 2)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Active Psoriatic Arthritis
Lead sponsor: Sun Pharmaceutical Industries Limited
Sponsor class: INDUSTRY
First posted: 2020-03-19
Enrollment: 296
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 .


Eligibility criteria: Inclusion Criteria:

1. Subject has provided written informed consent.
2. Subject is ≥ 18 years of age at time of Screening.
3. 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.
4. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP Ab) negative.
5. 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:

1. The subject has a planned surgical intervention between Baseline and the Week 52 evaluation for a pretreatment condition.
2. 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.
3. 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.
4. Subject has a known history of infection with hepatitis B, hepatitis C, or human immunodeficiency virus.
5. Subject had myocardial infarction, unstable angina pectoris, or ischemic stroke within the past 6 months prior to the first IMP dose.
6. Subject has any active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma.
7. Subjects with a history of alcohol or drug abuse in the previous 2 years.
8. 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.
9. 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).
10. Subject previously has been enrolled (randomized) in this study.
11. 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.
12. Donation or loss of 400 milliliter (mL) or more of blood within 8 weeks before first dose of IMP.
13. Subjects who have been placed in an institution on official or judicial orders.
14. Subjects who are related to or dependent on the Investigator, Sponsor, or study site such that a conflict of interest could arise.

Primary outcomes:
measure: The proportion of subjects who achieve American College of Rheumatology [ACR20]
timeFrame: at Week 24
Secondary outcomes:
measure: The proportion of subjects achieving American College of Rheumatology [ACR50]
timeFrame: at Week 24
measure: The proportion of subjects achieving American College of Rheumatology [ACR70]
timeFrame: at Week 24
measure: The proportion of subjects achieving Psoriasis Area and Severity Index 75 response among subjects with body surface area ≥3% at baseline
timeFrame: at Weeks 24
measure: The change from Baseline in the van der Heijde modified total Sharp score
timeFrame: Week 24
measure: The change from Baseline in the van der Heijde modified total Sharp score
timeFrame: at Week 16
measure: The Change from Baseline in American College of Rheumatology Response Criteria Components Score
timeFrame: at Week 24
measure: The change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index
timeFrame: at Week 24
measure: The change from Baseline in Leeds Enthesitis Index
timeFrame: at Week 24
measure: The change from Baseline in Leeds Dactylitis Index
timeFrame: at Week 24
measure: The proportion of subjects who achieve a Disease Activity Score-C-reactive protein < 3.2
timeFrame: at Week 24
measure: The change from Baseline in van der Heijde modified Sharp sub-scores (erosion score and joint space narrowing score)
timeFrame: at Week 24
measure: The proportion of subjects with the Change in van der Heijde modified total Sharp score <0 and < 0.5
timeFrame: Week 24
measure: The proportion of subjects with active Psoriasis and body surface area ≥3%
timeFrame: at Week 24
measure: The change from Baseline in anti-tumor necrosis factor naïve subjects with active Psoriasis and body surface area ≥ 3% (those with involvement of nails)
timeFrame: at Week 24
measure: The proportion of subjects achieving American College of Rheumatology [ACR20, ACR50 and ACR70]
timeFrame: at Week 52
measure: The change from Baseline in American College of Rheumatology Response Criteria Components Score
timeFrame: at week 52
measure: change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index
timeFrame: at Week 52
measure: The change from Baseline in Leeds Enthesitis Index, Leeds Dactylitis Index and Health Assessment Questionnaire Disability Index score
timeFrame: at Week 52
measure: The proportion of subjects who achieve a Disease Activity Score(28 [joints]-C-reactive protein) < 3.2
timeFrame: at Week 52
measure: The change from Baseline in van der Heijde modified total Sharp score
timeFrame: at Week 52
measure: The change from Baseline in van der Heijde modified Sharp sub-scores (erosion score and joint space narrowing score)
timeFrame: at Week 52
measure: The proportion of subjects with the change in van der Heijde modified total Sharp score <0 and < 0.5
timeFrame: at Week 52
measure: 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
timeFrame: at Week 52
measure: 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
timeFrame: at Week 52
measure: In anti-tumor necrosis factor naïve subjects with active Psoriasis and body surface area ≥3%, the change from Baseline in Physician Global Assessment-Psoriasis
timeFrame: at week 52
measure: Change from baseline in health assessment questionnaire - disability index (HAQ-DI) score
timeFrame: at Week 24
measure: The change from Baseline in the Short-Form-36 Health Survey Version 2 (SF-36v2), Acute Components
timeFrame: measured timepoints
measure: The change from Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scores
timeFrame: at week 24
Other outcomes:
measure: The proportion of subjects achieving American College of Rheumatology [ACR20]
timeFrame: exclusive of Weeks 24 and 52
measure: The proportion of subjects achieving American College of Rheumatology [ACR50]
timeFrame: exclusive of Weeks 24 and 52
measure: The proportion of subjects achieving American College of Rheumatology [ACR70]
timeFrame: exclusive of Weeks 24 and 52
measure: he change from Baseline in American College of Rheumatology Response Criteria Components Score
timeFrame: exclusive of Weeks 24 and 52
measure: The change from Baseline in Leeds Enthesitis Index, Leeds Dactylitis Index, Bath Ankylosing Spondylitis Disease Activity Index and Health Assessment Questionnaire Disability Index score
timeFrame: exclusive of Weeks 24 and 52
measure: The proportion of subjects who achieve a Disease Activity Score-C-reactive protein < 3.2
timeFrame: exclusive of Weeks 24 and 52
measure: The proportion of subjects with active Psoriasis and body surface area ≥ 3% with Psoriasis Area and Severity Index 75, Psoriasis Area and Severity Index 90 and Psoriasis Area and Severity Index 100
timeFrame: exclusive of Weeks 24 and 52
measure: The change from Baseline in the levels of "Metabolic Biomarkers"
timeFrame: at Week 24
measure: the change from baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA)
timeFrame: at Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 52
measure: proportion of subjects who achieve a response based on Modified Psoriatic Arthritis Responder Criteria (PsARC)
timeFrame: at Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 52.
measure: change from baseline in Work Productivity and Activity Impairment Questionnaire Scores
timeFrame: at Week 12,16 24, 48 and 52.
measure: change from baseline in Psoriatic Arthritis Disease Activity Score (PASDAS)
timeFrame: at Week 8,16, 24 and 52.
Locations:
city: Covina
country: United States
facility: Sunpharma site no. 12
state: California
city: Miami Beach
country: United States
facility: Sunpharma site no. 04
state: Florida
city: New Port Richey
country: United States
facility: Sunpharma site no. 02
state: Florida
city: Tamarac
country: United States
facility: Sunpharma site no. 07
state: Florida
city: Lake Charles
country: United States
facility: Sunpharma site no. 14
state: Louisiana
city: Springfield
country: United States
facility: Sunpharma site no. 05
state: Missouri
city: Lincoln
country: United States
facility: Sunpharma site no. 10
state: Nebraska
city: Greenville
country: United States
facility: Sunpharma site no. 11
state: South Carolina
city: Lubbock
country: United States
facility: Sunpharma site no. 09
state: Texas
city: San Antonio
country: United States
facility: Sunpharma site no. 03
state: Texas
city: Tomball
country: United States
facility: Sunpharma site no. 01
state: Texas
city: Spokane
country: United States
facility: Sunpharma site no. 06
state: Washington
city: Phillip
country: Australia
facility: Sunpharma Site 39
state: Australian Capital Territory
city: Maroochydore
country: Australia
facility: Sunpharma Site 16
state: Queensland
city: Hobart
country: Australia
facility: Sunpharma site no. 08
state: Tasmania
city: Fitzroy
country: Australia
facility: Sunpharma Site 101
state: Victoria
city: Brno
country: Czechia
facility: Sunpharma Site 64
city: Prague 2
country: Czechia
facility: Sunpharma Site 97
city: Praha 4
country: Czechia
facility: Sunpharma Site 102
city: Zlín
country: Czechia
facility: Sunpharma Site 63
city: Berlin
country: Germany
facility: Sunpharma Site 73
city: Herne
country: Germany
facility: Sunpharma Site 92
city: Surat
country: India
facility: Sunpharma Site 111
state: Gujarat
city: Bangalore
country: India
facility: Sunpharma Site 110
state: Karnataka
city: Belgaum
country: India
facility: Sunpharma Site 107
state: Karnataka
city: Hubli
country: India
facility: Sunpharma Site 109
state: Karnataka
city: Pune
country: India
facility: Sunpharma Site 108
state: Maharashtra
city: Hyderabad
country: India
facility: Sunpharma Site 112
state: Telangana
city: Lucknow
country: India
facility: Sunpharma Site 106
state: Uttar Pradesh
city: Cochin
country: India
facility: Sunpharma Site 113
city: Nagoya
country: Japan
facility: Sunpharma Site 84
state: Aichi
city: Kitakyushu
country: Japan
facility: Sunpharma Site 89
state: Fukuoka
city: Sendai
country: Japan
facility: Sunpharma Site 86
state: Miyagi
city: Miyazaki-shi
country: Japan
facility: Sunpharma Site 24
state: Miyazaki
city: Itabashi
country: Japan
facility: Sunpharma Site 90
state: Tokyo
city: Mitaka
country: Japan
facility: Sunpharma Site 91
state: Tokyo
city: Shinjuku
country: Japan
facility: Sunpharma Site 85
state: Tokyo
city: Kitakyushu-shi
country: Japan
facility: Sunpharma Site 22
city: Kumamoto
country: Japan
facility: Sunpharma Site 88
city: Osaka
country: Japan
facility: Sunpharma Site 87
city: Tsu-shi
country: Japan
facility: Sunpharma Site 23
city: Incheon
country: Korea, Republic of
facility: Sunpharma Site 18
city: Seoul
country: Korea, Republic of
facility: Sunpharma Site 20
city: Seoul
country: Korea, Republic of
facility: Sunpharma Site 19
city: Bialystok
country: Poland
facility: Sunpharma Site 95
city: Białystok
country: Poland
facility: Sunpharma Site 93
city: Lublin
country: Poland
facility: Sunpharma Site 94
city: Poznan
country: Poland
facility: Sunpharma Site 74
city: Warszawa
country: Poland
facility: Sunpharma Site 96
city: Córdoba
country: Spain
facility: Sunpharma Site 71
city: La Coruña
country: Spain
facility: Sunpharma Site 75
city: Madrid
country: Spain
facility: Sunpharma Site 100
city: Sevilla
country: Spain
facility: Sunpharma Site 72
city: Valencia
country: Spain
facility: Sunpharma Site 76
Study officials:
References: