A long-term extension study to investigate the safety and effectiveness of Tildrakizumab in patients with Psoriatic Arthritis and Ankylosing Spondylitis or Non-Radiographic Axial Spondyloarthritis who have previously completed other studies with Tildrakizumab

• Register: EUCTR
• Last refreshed on: 1 October 2018
• Main ID: EUCTR2018-001060-35-ES
• Date of registration: 17/07/2018
• Prospective Registration: Yes
• Primary sponsor: Sun Pharma Global FZE
• Public title: A long-term extension study to investigate the safety and effectiveness of Tildrakizumab in patients with Psoriatic Arthritis and Ankylosing Spondylitis or Non-Radiographic Axial Spondyloarthritis who have previously completed other studies with Tildrakizumab
• Scientific title: A Multiple-Dose, Long-Term Extension Study to Demonstrate the Safety and Efficacy of Tildrakizumab in Subjects with Psoriatic Arthritis and Ankylosing Spondylitis or Non-Radiographic Axial Spondyloarthritis who have previously completed studies with Tildrakizumab
• Date of first enrolment: 19/09/2018
• Target sample size: 540
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-001060-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Hungary, Mexico, Poland, Russian Federation, Spain, Ukraine, United States

Contacts

• Name: Mudgal Kothekar, MD
• Affiliation: Sun Pharma Advanced Research Company Limited

• Name: Mudgal Kothekar, MD
• Affiliation: Sun Pharma Advanced Research Company Limited

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects may be included in the study if they meet all of the following criteria:
1. Subject has provided written informed consent for this long-term extension study.
2. Subjects with PsA and AS or nr-axSpA who met the inclusion criteria of the parent studies and completed the parent study treatment period (e.g., up to Week 48 for the parent Phase 2 studies, with return for the EoT assessment at Week 52).
3. PsA subjects who achieved a 20% reduction from Baseline in ACR20 response criteria at Week 52, and AS or nr-axSpA subjects who achieved ASAS40 response criteria at Week 52, AND the subject has received sufficient clinical benefit, in the opinion of the Investigator, to support continued treatment with tildrakizumab.
This criteria using response criteria at Week 52 will apply to all subjects, including those subjects who enter the study from the wash-out phase of their parent study (after Week 52) due to the timing of study site activation of the long-term extension study.
4. No concomitant use of both leflunomide and methotrexate,
5. No history of active tuberculosis (TB) or symptoms of TB.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 540
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects should be excluded from the study if they meet any of the following criteria:
1. New onset during the parent study of arthritic conditions other than the subject's original condition.
2. 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 entering the study and through 16 weeks after the last dose of IMP. If a subject discontinues prematurely, the contraceptive method must be practiced for 16 weeks following final administration of IMP.
3. Female is pregnant or breastfeeding, or planning to become pregnant or initiate breastfeeding while enrolled in the study or up to 16 weeks after the last dose of IMP.
4. Subject has previously been enrolled in this long-term extension study.
5. Any condition that in the opinion of the Investigator represents an obstacle for study conduct and/or represents a potential unacceptable risk for the subject.
6. Subject has an active infection or history of infections as follows:
- a serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to the first IMP dose of the extension study, with the last dose having been received within 7 days of start of the extension study,
- 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 extension study to be detrimental to the subject.
7. Major chronic inflammatory or connective tissue disease other than PsA or AS/nr axSpA (e.g., rheumatoid arthritis, systemic lupus erythematosus, Lyme disease, and gout).
8. Known diagnosis of fibromyalgia, regional pain syndromes or active uveitis/symptomatic inflammatory bowel disease requiring therapy (AS/nr-axSpA subjects),
9. 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 continued treatment to be detrimental to the subject.
10. Subject has a known history of infection with hepatitis B, hepatitis C, or human immunodeficiency virus during the parent study
11. Subject had myocardial infarction, unstable angina pectoris, or ischemic stroke within the past 6 months prior to the first IMP dose for this extension study.
12. Subject has any active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma.
13. Subject has a history of malignancy EXCEPT treated and considered cured cutaneous basal or squamous cell carcinoma, in situ cervical carcinoma, OR in situ breast ductal carcinoma.
14. Subjects with a history of alcohol or drug abuse during the parent study.
15. Significant risk of suicidality at the Baseline assessment of this extension study based on the Investigator's judgment or, if appropriate, as indicated by a response of "yes" since the last visit to question 4 or 5 in the suicidal section, or any response in the b

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Psoriatic Arthritis (PsA), Ankylosing Spondylitis (AS) and Non-Radiographic Axial Spondyloarthritis (nr-axSpA)
MedDRA version: 20.0 Level: LLT Classification code 10037160 Term: Psoriatic arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
MedDRA version: 20.0 Level: PT Classification code 10002556 Term: Ankylosing spondylitis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
MedDRA version: 20.0 Level: LLT Classification code 10076297 Term: Non-radiographic axial spondyloarthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Product Name: Tildrakizumab 100 mg/ml
Product Code: MK-3222
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Tildrakizumab
CAS Number: 1326244-10-3
Current Sponsor code: MK-3222
Other descriptive name: Anti-Human Interleukin-23 Monoclonal Antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): Efficacy:
For PsA subjects:
• The proportion of subjects who achieve ACR20 at measured time points.
• The proportion of subjects who achieve ACR50 at measured time points.
• The proportion of subjects who achieve ACR70 at measured time points.
• Individual components of ACR response at measured time points:
- tender joint counts (68)
- swollen joint counts (66)
- PGA of disease activity (VAS)
- Patient Global Assessment of disease activity (VAS)
- patient's pain assessment (VAS)
- patient's self-assessed disability (Health Assessment Questionnaire Disability Index)
- acute-phase high sensitivity C-reactive protein (CRP)
- erythrocyte sedimentation rate
• SF-36 at measured time points.
For AS or nr-axSpA subjects:
• The proportion of subjects who achieve ASAS20 at measured time points.
• The proportion of subjects who achieve ASAS40 at measured time points.
• The proportion of subjects who achieve ASAS70 at measured time points.
• The proportion of subjects who achieve an ASAS5/6 response at measured time points.
ASAS5/6 response is defined as a 20% improvement in 5 out of 6 domains (physical function [BASFI], Total Back Pain, Patient's Global Assessment of Disease Activity, Inflammation [average i.e., mean score of Questions 5 and 6 of the BASDAI], spinal mobility [Bath Ankylosing Spondylitis Metrology Index [BASMI], and acute-phase reactants [CRP]).
• Individual ASAS components at measured time points:
- PtGA of disease activity (VAS in mm),
- total back pain (VAS in mm),
- BASFI (VAS in mm),
- inflammation (mean score of questions 5 and 6 of BASDAI) (VAS in mm).
• BASDAI at measured time points.
• VAS (total back pain and nocturnal pain score) at measured time points.
• BASMI at measured time points.
• TJC46 and SJC44 at measured time points
• SF-36 at measured time points.

Secondary Objective: To evaluate long-term treatment outcomes of tildrakizumab in adults with PsA by evaluation of:
• ACR20, ACR50, ACR70, the components of ACR, and 36-item Short Form (SF-36) at other measured time points.
To evaluate long-term treatment outcomes of tildrakizumab in adults with AS or nr-axSpA by evaluation of:
• The proportion of subjects who achieve ASAS20 or ASAS40 at measured time points.
• The proportion of subjects who achieve ASAS70 or ASAS5/6 at measured time points.
• The 46-item tender joint counts (TJC)46 and 44-item swollen joint counts (SJC)44,
ASAS components, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), total back pain and nocturnal pain score using a visual analog scale (VAS), and SF-36 at measured time points.

Timepoint(s) of evaluation of this end point: Please refer to the Schedule of Assessments in the protocol (Table 9-1 and 9-2)

Main Objective: Safety:
To assess the long-term safety of tildrakizumab when administered to PsA and AS or nr-axSpA subjects by evaluation of:
• Incidence and intensity of all AEs,
• Changes in vital signs, laboratory assessments, electrocardiograms (ECGs), and Columbia-Suicide Severity Rating Scale (C-SSRS),
• Immunogenicity of multiple-dose administration of tildrakizumab in these subjects.
Efficacy:
To assess the long-term efficacy of multiple-dose administration of tildrakizumab in subjects with PsA and AS or nr-axSpA by evaluation of:
• PsA subjects: The proportion of subjects achieving a 20% reduction from Baseline in American College of Rheumatology response criteria (ACR20) at measured time points.
• AS/nr-axSpA subjects: The proportion of subjects achieving Assessment of SpondyloArthritis International Society (ASAS) 40 response criteria at measured time points.
Baseline is defined as Week 0 (Day 1) of the parent study for both ACR20 and ASAS40 response criteria.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Please refer to the Schedule of Assessments in the protocol (Table 9-1 and 9-2)

Secondary end point(s): Pharmacokinetics: Serum tildrakizumab concentration data.
Safety: The following data will be collected for assessment of safety:
• AEs.
• Laboratory assessments.
• Suicidal ideation and behavior (C-SSRS).
• Vital signs.
• Electrocardiogram.
• Physical examination.
• ADA to tildrakizumab

Secondary ID(s)

CLR_18_07

2018-001060-35-HU

Source(s) of Monetary Support

Sun Pharma Global FZE