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

Active Psoriatic Arthritis Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04314531
• Other study ID #: TILD-19-19
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 1, 2020
• Est. completion date: December 2024

Study information

• Verified date: June 2024
• Source: Sun Pharmaceutical Industries Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 .

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 292
• Est. completion date: December 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Active Psoriatic Arthritis
• Arthritis
• Arthritis, Psoriatic

Intervention

Drug:
• TILD
one 1 mL injection of study medication
• matching placebo injections
one 1 mL injection of placebo

Locations

Country	Name	City	State
Australia	Sunpharma Site 101	Fitzroy	Victoria
Australia	Sunpharma site no. 08	Hobart	Tasmania
Australia	Sunpharma Site 16	Maroochydore	Queensland
Australia	Sunpharma Site 39	Phillip	Australian Capital Territory
Czechia	Sunpharma Site 64	Brno
Czechia	Sunpharma Site 97	Prague 2
Czechia	Sunpharma Site 102	Praha 4
Czechia	Sunpharma Site 63	Zlín
Germany	Sunpharma Site 73	Berlin
Germany	Sunpharma Site 92	Herne
India	Sunpharma Site 110	Bangalore	Karnataka
India	Sunpharma Site 107	Belgaum	Karnataka
India	Sunpharma Site 113	Cochin
India	Sunpharma Site 109	Hubli	Karnataka
India	Sunpharma Site 112	Hyderabad	Telangana
India	Sunpharma Site 106	Lucknow	Uttar Pradesh
India	Sunpharma Site 108	Pune	Maharashtra
India	Sunpharma Site 111	Surat	Gujarat
Japan	Sunpharma Site 90	Itabashi	Tokyo
Japan	Sunpharma Site 89	Kitakyushu	Fukuoka
Japan	Sunpharma Site 22	Kitakyushu-shi
Japan	Sunpharma Site 88	Kumamoto
Japan	Sunpharma Site 91	Mitaka	Tokyo
Japan	Sunpharma Site 24	Miyazaki-shi	Miyazaki
Japan	Sunpharma Site 84	Nagoya	Aichi
Japan	Sunpharma Site 87	Osaka
Japan	Sunpharma Site 86	Sendai	Miyagi
Japan	Sunpharma Site 85	Shinjuku	Tokyo
Japan	Sunpharma Site 23	Tsu-shi
Korea, Republic of	Sunpharma Site 104	Daejeon
Korea, Republic of	Sunpharma Site 21	Gyeonggi-do
Korea, Republic of	Sunpharma Site 18	Incheon
Korea, Republic of	Sunpharma Site 19	Seoul
Korea, Republic of	Sunpharma Site 20	Seoul
Poland	Sunpharma Site 93	Bialystok
Poland	Sunpharma Site 95	Bialystok
Poland	Sunpharma Site 94	Lublin
Poland	Sunpharma Site 74	Poznan
Poland	Sunpharma Site 96	Warszawa
Spain	Sunpharma Site 71	Córdoba
Spain	Sunpharma Site 75	La Coruña
Spain	Sunpharma Site 100	Madrid
Spain	Sunpharma Site 72	Sevilla
Spain	Sunpharma Site 76	Valencia
United States	Sunpharma site no. 12	Covina	California
United States	Sunpharma site no. 11	Greenville	South Carolina
United States	Sunpharma site no. 14	Lake Charles	Louisiana
United States	Sunpharma site no. 10	Lincoln	Nebraska
United States	Sunpharma site no. 09	Lubbock	Texas
United States	Sunpharma site no. 04	Miami Beach	Florida
United States	Sunpharma site no. 02	New Port Richey	Florida
United States	Sunpharma site no. 03	San Antonio	Texas
United States	Sunpharma site no. 06	Spokane	Washington
United States	Sunpharma site no. 05	Springfield	Missouri
United States	Sunpharma site no. 07	Tamarac	Florida
United States	Sunpharma site no. 01	Tomball	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Sun Pharmaceutical Industries Limited

Countries where clinical trial is conducted

United States,  Australia,  Czechia,  Germany,  India,  Japan,  Korea, Republic of,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	The proportion of subjects who achieve a Disease Activity Score-C-reactive protein < 3.2		exclusive of Weeks 24 and 52
Other	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
Other	The change from Baseline in the levels of "Metabolic Biomarkers"		at Week 24
Other	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
Other	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.
Other	change from baseline in Work Productivity and Activity Impairment Questionnaire Scores		at Week 12,16 24, 48 and 52.
Other	change from baseline in Psoriatic Arthritis Disease Activity Score (PASDAS)		at Week 8,16, 24 and 52.
Primary	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	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
Secondary	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
Secondary	The proportion of subjects achieving Psoriasis Area and Severity Index 75 response among subjects with body surface area =3% at baseline		at Weeks 24
Secondary	The change from Baseline in the van der Heijde modified total Sharp score		Week 24
Secondary	The change from Baseline in the van der Heijde modified total Sharp score		at Week 16
Secondary	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
Secondary	The change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index		at Week 24
Secondary	The change from Baseline in Leeds Enthesitis Index		at Week 24
Secondary	The change from Baseline in Leeds Dactylitis Index		at Week 24
Secondary	The proportion of subjects who achieve a Disease Activity Score-C-reactive protein < 3.2		at Week 24
Secondary	The change from Baseline in van der Heijde modified Sharp sub-scores (erosion score and joint space narrowing score)		at Week 24
Secondary	The proportion of subjects with the Change in van der Heijde modified total Sharp score <0 and < 0.5		Week 24
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index		at Week 52
Secondary	The change from Baseline in Leeds Enthesitis Index, Leeds Dactylitis Index and Health Assessment Questionnaire Disability Index score		at Week 52
Secondary	The proportion of subjects who achieve a Disease Activity Score(28 [joints]-C-reactive protein) < 3.2		at Week 52
Secondary	The change from Baseline in van der Heijde modified total Sharp score		at Week 52
Secondary	The change from Baseline in van der Heijde modified Sharp sub-scores (erosion score and joint space narrowing score)		at Week 52
Secondary	The proportion of subjects with the change in van der Heijde modified total Sharp score <0 and < 0.5		at Week 52
Secondary	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
Secondary	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
Secondary	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
Secondary	Change from baseline in health assessment questionnaire - disability index (HAQ-DI) score		at Week 24
Secondary	The change from Baseline in the Short-Form-36 Health Survey Version 2 (SF-36v2), Acute Components		measured timepoints
Secondary	The change from Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scores		at week 24