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

• Sponsor: Sun Pharmaceutical Industries Limited (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04314531
• Collaborator: (none)
• Enrollment: 292
• Locations: 90
• Arms: 2
• Anticipated Duration (Months): 34
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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 .

Condition or Disease	Intervention/Treatment	Phase
Active Psoriatic Arthritis	Drug: TILD; Drug: matching placebo injections	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 292 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Jul 1, 2020
• Anticipated Primary Completion Date: Sep 30, 2022
• Anticipated Study Completion Date: May 1, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. The proportion of subjects who achieve American College of Rheumatology [ACR20] [at Week 24]

   the proportion of subjects achieving a 20% reduction from Baseline in response criteria

Secondary Outcome Measures

1. The proportion of subjects achieving American College of Rheumatology [ACR50] [at Week 24]

   the proportion of subjects achieving a 50% reduction from Baseline in response criteria

2. The proportion of subjects achieving American College of Rheumatology [ACR70] [at Week 24]

   the proportion of subjects achieving a 70% reduction from Baseline in response criteria

3. The proportion of subjects achieving Psoriasis Area and Severity Index 75 response among subjects with body surface area ≥3% at baseline [at Weeks 24]

4. The change from Baseline in the van der Heijde modified total Sharp score [Week 24]

5. The change from Baseline in the van der Heijde modified total Sharp score [at Week 16]

6. The Change from Baseline in American College of Rheumatology Response Criteria Components Score [at Week 24]

   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

7. The change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index [at Week 24]

8. The change from Baseline in Leeds Enthesitis Index [at Week 24]

9. The change from Baseline in Leeds Dactylitis Index [at Week 24]

10. The proportion of subjects who achieve a Disease Activity Score-C-reactive protein < 3.2 [at Week 24]

11. The change from Baseline in van der Heijde modified Sharp sub-scores (erosion score and joint space narrowing score) [at Week 24]

12. The proportion of subjects with the Change in van der Heijde modified total Sharp score <0 and < 0.5 [Week 24]

13. The proportion of subjects with active Psoriasis and body surface area ≥3% [at Week 24]

    Psoriasis Area and Severity Index 90 and Psoriasis Area and Severity Index 100

14. The change from Baseline in anti-tumor necrosis factor naïve subjects with active Psoriasis and body surface area ≥ 3% (those with involvement of nails) [at Week 24]

    Physician Global Assessment-Psoriasis and nail psoriasis severity index

15. The proportion of subjects achieving American College of Rheumatology [ACR20, ACR50 and ACR70] [at Week 52]

    the proportion of subjects achieving a 20/50/70% reduction from Baseline in response criteria

16. The change from Baseline in American College of Rheumatology Response Criteria Components Score [at week 52]

    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

17. change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index [at Week 52]

18. The change from Baseline in Leeds Enthesitis Index, Leeds Dactylitis Index and Health Assessment Questionnaire Disability Index score [at Week 52]

19. The proportion of subjects who achieve a Disease Activity Score(28 [joints]-C-reactive protein) < 3.2 [at Week 52]

20. The change from Baseline in van der Heijde modified total Sharp score [at Week 52]

21. The change from Baseline in van der Heijde modified Sharp sub-scores (erosion score and joint space narrowing score) [at Week 52]

22. The proportion of subjects with the change in van der Heijde modified total Sharp score <0 and < 0.5 [at Week 52]

23. 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]

24. 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]

25. 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]

26. Change from baseline in health assessment questionnaire - disability index (HAQ-DI) score [at Week 24]

27. The change from Baseline in the Short-Form-36 Health Survey Version 2 (SF-36v2), Acute Components [measured timepoints]

28. The change from Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scores [at week 24]

Other Outcome Measures

1. The proportion of subjects achieving American College of Rheumatology [ACR20] [exclusive of Weeks 24 and 52]

   the proportion of subjects achieving a 20% reduction from Baseline in response criteria

2. The proportion of subjects achieving American College of Rheumatology [ACR50] [exclusive of Weeks 24 and 52]

   the proportion of subjects achieving a 50% reduction from Baseline in response criteria

3. The proportion of subjects achieving American College of Rheumatology [ACR70] [exclusive of Weeks 24 and 52]

   the proportion of subjects achieving a 70% reduction from Baseline in response criteria

4. he change from Baseline in American College of Rheumatology Response Criteria Components Score [exclusive of Weeks 24 and 52]

   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

5. 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]

6. The proportion of subjects who achieve a Disease Activity Score-C-reactive protein < 3.2 [exclusive of Weeks 24 and 52]

7. 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]

8. The change from Baseline in the levels of "Metabolic Biomarkers" [at Week 24]

9. 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]

10. 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.]

11. change from baseline in Work Productivity and Activity Impairment Questionnaire Scores [at Week 12,16 24, 48 and 52.]

12. change from baseline in Psoriatic Arthritis Disease Activity Score (PASDAS) [at Week 8,16, 24 and 52.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. 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.

2. Subject has a known history of infection with hepatitis B, hepatitis C, or human immunodeficiency virus.

3. Subject had myocardial infarction, unstable angina pectoris, or ischemic stroke within the past 6 months prior to the first IMP dose.

4. Subject has any active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma.

5. Subjects with a history of alcohol or drug abuse in the previous 2 years.

6. 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.

7. 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).

8. Subject previously has been enrolled (randomized) in this study.

9. 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.

10. Donation or loss of 400 milliliter (mL) or more of blood within 8 weeks before first dose of IMP.

11. Subjects who have been placed in an institution on official or judicial orders.

12. Subjects who are related to or dependent on the Investigator, Sponsor, or study site such that a conflict of interest could arise.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sunpharma Site 58	Anniston	Alabama	United States	36207
2	Sunpharma Site 53	Dothan	Alabama	United States	36305
3	Sunpharma Site 42	Gilbert	Arizona	United States	85297
4	Sunpharma Site 43	Glendale	Arizona	United States	85032
5	Sunpharma Site 44	Phoenix	Arizona	United States	85210
6	Sunpharma Site 54	Scottsdale	Arizona	United States	85258
7	Sunpharma site no. 12	Covina	California	United States	91722
8	Sunpharma Site 60	Encino	California	United States	91436
9	Sunpharma Site 34	Fountain Valley	California	United States	92708
10	Sunpharma Site 33	Thousand Oaks	California	United States	91320
11	Sunpharma Site 51	Denver	Colorado	United States	80230
12	Sunpharma Site 47	Fort Collins	Colorado	United States	80528
13	Sunpharma Site 45	Bridgeport	Connecticut	United States	06606
14	Sunpharma Site 38	Clearwater	Florida	United States	33765
15	Sunpharma site no. 04	Hialeah	Florida	United States	33016
16	Sunpharma Site 50	Hollywood	Florida	United States	33024
17	Sunpharma Site 69	Kissimmee	Florida	United States	34741
18	Sunpharma Site 36	Miami	Florida	United States	33135
19	Sunpharma site no. 02	New Port Richey	Florida	United States	34652
20	Sunpharma site no. 07	Tamarac	Florida	United States	33321
21	Sunpharma site no. 13	Decatur	Georgia	United States	30033
22	Sunpharma Site 57	Gainesville	Georgia	United States	30501
23	Sunpharma Site 52	Morton Grove	Illinois	United States	60523
24	Sunpharma Site 68	Orland Park	Illinois	United States	60467
25	Sunpharma Site 49	Schaumburg	Illinois	United States	60185
26	Sunpharma Site 48	Skokie	Illinois	United States	60076
27	Sunpharma Site 37	Wichita	Kansas	United States	67207
28	Sunpharma site no. 14	Lake Charles	Louisiana	United States	70605
29	Sunpharma Site 27	Worcester	Massachusetts	United States	01605
30	Sunpharma Site 30	Lansing	Michigan	United States	48910
31	Sunpharma Site 56	Eagan	Minnesota	United States	55121
32	Sunpharma site no. 05	Springfield	Missouri	United States	65810
33	Sunpharma Site 67	Kalispell	Montana	United States	59901
34	Sunpharma site no. 10	Lincoln	Nebraska	United States	68516
35	Sunpharma Site 55	Voorhees	New Jersey	United States	08043
36	Sunpharma Site 29	Rochester	New York	United States	14623
37	Sunpharma Site 66	Charlotte	North Carolina	United States	28204
38	Sunpharma Site 70	Wilmington	North Carolina	United States	28401
39	Sunpharma Site 46	Minot	North Dakota	United States	58701
40	Sunpharma Site 35	Cincinnati	Ohio	United States	45242
41	Sunpharma Site 31	Middleburg Heights	Ohio	United States	44130
42	Sunpharma Site 41	Wyomissing	Pennsylvania	United States	19610
43	Sunpharma site no. 11	Greenville	South Carolina	United States	29601
44	Sunpharma Site 62	Austin	Texas	United States	78745
45	Sunpharma Site 32	Baytown	Texas	United States	77521
46	Sunpharma Site 61	Grapevine	Texas	United States	76051
47	Sunpharma Site 26	Houston	Texas	United States	77004
48	Sunpharma Site 28	Houston	Texas	United States	77084
49	Sunpharma Site 25	League City	Texas	United States	77573
50	Sunpharma site no. 09	Lubbock	Texas	United States	79410
51	Sunpharma site no. 03	San Antonio	Texas	United States	78229
52	Sunpharma site no. 01	Tomball	Texas	United States	77375
53	Sunpharma site no. 06	Spokane	Washington	United States	99204
54	Sunpharma Site 39	Phillip	Australian Capital Territory	Australia	2606
55	Sunpharma Site 40	Kogarah	New South Wales	Australia	2217
56	Sunpharma Site 16	Maroochydore	Queensland	Australia	4558
57	Sunpharma Site 17	Hobart	Tasmania	Australia	7000
58	Sunpharma site no. 08	Hobart	Tasmania	Australia	7000
59	Sunpharma Site 15	Camberwell	Victoria	Australia	3145
60	Sunpharma Site 64	Brno		Czechia	638 00
61	Sunpharma Site 63	Zlín		Czechia	760 01
62	Sunpharma Site 73	Berlin		Germany	12161
63	Sunpharma Site 84	Nagoya	Aichi	Japan	467-0001
64	Sunpharma Site 89	Kitakyushu	Fukuoka	Japan	802-8561
65	Sunpharma Site 86	Sendai	Miyagi	Japan	980-8574
66	Sunpharma Site 24	Miyazaki-shi	Miyazaki	Japan	889-1692
67	Sunpharma Site 90	Itabashi	Tokyo	Japan	173-8606
68	Sunpharma Site 91	Mitaka	Tokyo	Japan	181-8611
69	Sunpharma Site 85	Shinjuku	Tokyo	Japan	160-0023
70	Sunpharma Site 22	Kitakyushu-shi		Japan	802-8561
71	Sunpharma Site 88	Kumamoto		Japan	860-8556
72	Sunpharma Site 87	Osaka		Japan	545-0051
73	Sunpharma Site 23	Tsu-shi		Japan	514-8507
74	Sunpharma Site 18	Incheon		Korea, Republic of	22332
75	Sunpharma Site 20	Seoul		Korea, Republic of	3080
76	Sunpharma Site 19	Seoul		Korea, Republic of	4763
77	Sunpharma Site 21	Suwon		Korea, Republic of	16499
78	Sunpharma Site 74	Poznan		Poland	61-113
79	Sunpharma Site 71	Córdoba		Spain	14004
80	Sunpharma Site 75	La Coruña		Spain	15006
81	Sunpharma Site 72	Sevilla		Spain	41013
82	Sunpharma Site 76	Valencia		Spain	46010
83	Sunpharma Site 65	Valencia		Spain	46026
84	Sunpharma Site 80	Jianguo	Taichung	Taiwan	402
85	Sunpharma Site 79	Kaohsiung		Taiwan	833
86	Sunpharma Site 78	Taichung		Taiwan	704
87	Sunpharma Site 77	Tainan		Taiwan	710
88	Sunpharma Site 81	Taipei		Taiwan	112
89	Sunpharma Site 82	Taipei		Taiwan	112
90	Sunpharma Site 83	Taipei		Taiwan	114

Sponsors and Collaborators

• Sun Pharmaceutical Industries Limited

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sun Pharmaceutical Industries Limited
• ClinicalTrials.gov Identifier: NCT04314531
• Other Study ID Numbers: TILD-19-19
• First Posted: Mar 19, 2020
• Last Update Posted: Aug 17, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Arthritis; Arthritis, Psoriatic

Study Results

No Results Posted as of Aug 17, 2022