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

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)

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 .

Study Overview

• Status: Active, not recruiting
• Conditions: Active Psoriatic Arthritis
• Intervention / Treatment: Drug: TILD; Drug: matching placebo injections

• Study Type: Interventional
• Enrollment (Actual): 292
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Head, Clinical development; Phone Number: 5689 91 2266455645; Email: Clinical.Trial@sunpharma.com

Study Locations

• Australia
  • Australian Capital Territory
    • Phillip, Australian Capital Territory, Australia, 2606
      • Sunpharma Site 39
  • Queensland
    • Maroochydore, Queensland, Australia, 4558
      • Sunpharma Site 16
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Sunpharma site no. 08
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Sunpharma Site 101
• Czechia
  • Brno, Czechia, 638 00
    • Sunpharma Site 64
  • Prague 2, Czechia, 12800
    • Sunpharma Site 97
  • Praha 4, Czechia, 140 00
    • Sunpharma Site 102
  • Zlín, Czechia, 760 01
    • Sunpharma Site 63
• Germany
  • Berlin, Germany, 12161
    • Sunpharma Site 73
  • Herne, Germany, 44649
    • Sunpharma Site 92
• India
  • Gujarat
    • Surat, Gujarat, India, 395010
      • Sunpharma Site 111
  • Karnataka
    • Bangalore, Karnataka, India, 560079
      • Sunpharma Site 110
    • Belgaum, Karnataka, India, 590016
      • Sunpharma Site 107
    • Hubli, Karnataka, India, 580021
      • Sunpharma Site 109
  • Maharashtra
    • Pune, Maharashtra, India, 411004
      • Sunpharma Site 108
  • Telangana
    • Hyderabad, Telangana, India, 500003
      • Sunpharma Site 112
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226003
      • Sunpharma Site 106
• Japan
  • Kitakyushu-shi, Japan, 802-8561
    • Sunpharma Site 22
  • Kumamoto, Japan, 860-8556
    • Sunpharma Site 88
  • Osaka, Japan, 545-0051
    • Sunpharma Site 87
  • Tsu-shi, Japan, 514-8507
    • Sunpharma Site 23
  • Aichi
    • Nagoya, Aichi, Japan, 467-0001
      • Sunpharma Site 84
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan, 802-8561
      • Sunpharma Site 89
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
      • Sunpharma Site 86
  • Miyazaki
    • Miyazaki-shi, Miyazaki, Japan, 889-1692
      • Sunpharma Site 24
  • Tokyo
    • Itabashi, Tokyo, Japan, 173-8606
      • Sunpharma Site 90
    • Mitaka, Tokyo, Japan, 181-8611
      • Sunpharma Site 91
    • Shinjuku, Tokyo, Japan, 160-0023
      • Sunpharma Site 85
• Korea, Republic of
  • Daejeon, Korea, Republic of, 35015
    • Sunpharma Site 104
  • Gyeonggi-do, Korea, Republic of, 16499
    • Sunpharma Site 21
  • Incheon, Korea, Republic of, 22332
    • Sunpharma Site 18
  • Seoul, Korea, Republic of, 3080
    • Sunpharma Site 20
  • Seoul, Korea, Republic of, 4763
    • Sunpharma Site 19
• Poland
  • Bialystok, Poland, 15-879
    • Sunpharma Site 95
  • Białystok, Poland, 15-351
    • Sunpharma Site 93
  • Lublin, Poland, 20-607
    • Sunpharma Site 94
  • Poznan, Poland, 61-113
    • Sunpharma Site 74
  • Warszawa, Poland, 02-118
    • Sunpharma Site 96
• Spain
  • Córdoba, Spain, 14004
    • Sunpharma Site 71
  • La Coruña, Spain, 15006
    • Sunpharma Site 75
  • Madrid, Spain, 28046
    • Sunpharma Site 100
  • Sevilla, Spain, 41013
    • Sunpharma Site 72
  • Valencia, Spain, 46010
    • Sunpharma Site 76
• United States
  • California
    • Covina, California, United States, 91722
      • Sunpharma site no. 12
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Sunpharma site no. 04
    • New Port Richey, Florida, United States, 34652
      • Sunpharma site no. 02
    • Tamarac, Florida, United States, 33321
      • Sunpharma site no. 07
  • Louisiana
    • Lake Charles, Louisiana, United States, 70605
      • Sunpharma site no. 14
  • Missouri
    • Springfield, Missouri, United States, 65810
      • Sunpharma site no. 05
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Sunpharma site no. 10
  • South Carolina
    • Greenville, South Carolina, United States, 29601
      • Sunpharma site no. 11
  • Texas
    • Lubbock, Texas, United States, 79410
      • Sunpharma site no. 09
    • San Antonio, Texas, United States, 78229
      • Sunpharma site no. 03
    • Tomball, Texas, United States, 77375
      • Sunpharma site no. 01
  • Washington
    • Spokane, Washington, United States, 99204
      • Sunpharma site no. 06

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A	Drug: TILD; one 1 mL injection of study medication
Placebo Comparator: Arm B	Drug: matching placebo injections; one 1 mL injection of placebo

What is the study measuring?

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 change from Baseline in the van der Heijde modified total Sharp score		at Week 16
The change from Baseline in Leeds Dactylitis Index		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 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
Change from baseline in health assessment questionnaire - disability index (HAQ-DI) score		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 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 proportion of subjects who achieve a Disease Activity Score-C-reactive protein < 3.2		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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change from Baseline in the levels of "Metabolic Biomarkers"		at Week 24
the change from baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA)		at Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 52
proportion of subjects who achieve a response based on Modified Psoriatic Arthritis Responder Criteria (PsARC)		at Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 52.
change from baseline in Psoriatic Arthritis Disease Activity Score (PASDAS)		at Week 8,16, 24 and 52.
The proportion of subjects achieving American College of Rheumatology [ACR20]	the proportion of subjects achieving a 20% reduction from Baseline in response criteria	exclusive of Weeks 24 and 52
The proportion of subjects achieving American College of Rheumatology [ACR50]	the proportion of subjects achieving a 50% reduction from Baseline in response criteria	exclusive of Weeks 24 and 52
The proportion of subjects achieving American College of Rheumatology [ACR70]	the proportion of subjects achieving a 70% reduction from Baseline in response criteria	exclusive of Weeks 24 and 52
he 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	exclusive of Weeks 24 and 52
The change from Baseline in Leeds Enthesitis Index, Leeds Dactylitis Index, Bath Ankylosing Spondylitis Disease Activity Index and Health Assessment Questionnaire Disability Index score		exclusive of Weeks 24 and 52
The proportion of subjects who achieve a Disease Activity Score-C-reactive protein < 3.2		exclusive of Weeks 24 and 52
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		exclusive of Weeks 24 and 52
change from baseline in Work Productivity and Activity Impairment Questionnaire Scores		at Week 12,16 24, 48 and 52.

Collaborators and Investigators

• Sponsor: Sun Pharmaceutical Industries Limited

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: March 13, 2020
• First Submitted That Met QC Criteria: March 17, 2020
• First Posted (Actual): March 19, 2020

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic
• Other Study ID Numbers: TILD-19-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No