Phase 3 Randomized Double-Blind Study on Efficacy and Safety of Subcutaneous Tildrakizumab in Moderate to Severe Genital Psoriasis

Trial ID: 2024-515672-12-00
Protocol: TILD-24-01
Sponsor: Sun Pharmaceutical Industries Limited

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Diseases & Conditions

Psoriasis

Objectives

The primary objective of this Phase 3, randomized, double-blind, placebo-controlled, multicenter study is to evaluate the clinical efficacy of **subcutaneous (SC) tildrakizumab** compared to placebo in subjects with moderate to severe genital psoriasis. This is assessed over a 16-week period using the modified static Physician’s Global Assessment of Genitalia (sPGA-G) scores. The clinical relevance of this objective lies in its potential to provide a new therapeutic option for patients suffering from this condition, which can significantly impact quality of life.

Secondary objectives include evaluating the clinical efficacy of SC tildrakizumab versus placebo at Week 16 on plaque psoriasis, as measured by body surface area (BSA) and psoriasis area and severity index (PASI). Additionally, the study aims to assess the impact on genital itch, using the genital psoriasis itch numerical rating scale (GPI-NRS), and genital psoriasis symptoms, as measured by the genital psoriasis symptoms scale (GPSS). These secondary objectives are crucial for understanding the broader effects of tildrakizumab on psoriasis symptoms beyond the genital area.

Participants

The clinical trial involves a total of **132 participants** diagnosed with **moderate to severe genital psoriasis**. The study population includes both male and female subjects, aged 18 years and older, who are in good health except for their psoriasis condition. Participants were selected based on their ability to understand the trial's purpose and risks, willingness to comply with the protocol, and provision of written informed consent. Key lifestyle considerations include the presence of non-genital plaque psoriasis and inadequately controlled genital psoriasis with topical therapy. The trial population is not limited by gender, and both male and female subjects are included. The study also considers vulnerable populations, ensuring comprehensive evaluation and care. Participants must have a negative evaluation for tuberculosis and, for women of childbearing potential, a negative pregnancy test prior to the first dose of study medication. The selection criteria ensure that participants are physically examined and deemed in good health by the investigator, based on medical history and clinical assessments.

Plans and Procedures

The clinical trial is a **Phase 3**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of subcutaneous **tildrakizumab** in subjects with moderate to severe genital psoriasis. The trial aims to assess the clinical efficacy of tildrakizumab compared to placebo over a 16-week period, as measured by modified static Physician’s Global Assessment of Genitalia (sPGA-G) scores. The study is expected to commence recruitment on March 1, 2025, and conclude by April 20, 2027.

Participants will be randomly assigned to receive either tildrakizumab or a placebo, with the intervention administered subcutaneously. The trial will include several key visits: an initial screening visit to confirm eligibility, baseline assessments, and subsequent follow-up visits to monitor progress and collect data on primary and secondary endpoints. The primary endpoint is the proportion of subjects achieving a modified sPGA-G score of clear (0) or almost clear (1) with at least a 2-point reduction from baseline at week 16. Secondary endpoints include improvements in the Genital Psoriasis Itch Numeric Rating Scale (GPI-NRS), changes in affected Body Surface Area (BSA), and Psoriasis Area and Severity Index (PASI) responses.

Participants are expected to be involved in the study for a maximum of 52 weeks, which includes the treatment and follow-up periods. Conditions that may lead to early termination from the study include non-compliance with the protocol, adverse events, or withdrawal of consent. The trial is structured to ensure rigorous data collection and analysis, maintaining the integrity and reliability of the results. The study is not classified as a low-intervention trial, reflecting its comprehensive design and the need for close monitoring of participants throughout the trial duration.

Treatment

The clinical trial involves the administration of **Tildrakizumab**, an experimental medication, which is a **solution for injection**. The active substance in this medication is **tildrakizumab**, a protein of other origin. The pharmaceutical form is a solution intended for subcutaneous administration. The dosage is set at a maximum of 100 mg per day, with a total maximum dose of 100 mg. The treatment period extends up to 52 weeks. The medication is not formulated for pediatric use and is identified by the European Union marketing authorization number EU/1/18/1323/001. The administration schedule and participant compliance are monitored throughout the study to ensure adherence to the dosing regimen.

In addition to the experimental medication, a **placebo** is used as a comparator in this double-blind, placebo-controlled study. The placebo is also a solution for injection, designed to mimic the administration of tildrakizumab without containing the active substance. The placebo is administered subcutaneously, following the same dosing schedule as the experimental treatment, to maintain the study's blinding integrity. The use of a placebo allows for the evaluation of the efficacy and safety of tildrakizumab in subjects with moderate to severe genital psoriasis, as measured by the modified static Physician’s Global Assessment of Genitalia (sPGA-G) scores over a 16-week period.

Efficacy

The efficacy of subcutaneous **tildrakizumab** in subjects with moderate to severe genital psoriasis will be assessed in a Phase 3, randomized, double-blind, placebo-controlled study. The primary endpoint for evaluating efficacy is the proportion of subjects achieving a modified static Physician’s Global Assessment of Genitalia (sPGA-G) score of clear (0) or almost clear (1) with at least a 2-point reduction from baseline at week 16. Secondary endpoints include:

Proportion of subjects with a baseline score of ≥4 achieving at least a 4-point improvement in the weekly average of the Genital Psoriasis Itch Numeric Rating Scale (GPI-NRS).
Mean change from baseline in the affected Body Surface Area (BSA).
Change from baseline in the Genital Psoriasis Symptoms Scale (GPSS) total score and individual item scores.
Proportion of subjects achieving PASI 75 response (≥75% reduction from baseline in Psoriasis Area and Severity Index score).
Proportion of subjects achieving PASI 90 response (≥90% reduction from baseline in PASI score).
Proportion of subjects achieving PASI 100 response (100% reduction from baseline in PASI score) in subjects with BSA <10%.

These efficacy parameters will be measured and collected at specified timepoints, including baseline and week 16, using validated scales and assessments. The analysis will focus on comparing the outcomes between the tildrakizumab and placebo groups to determine the treatment's efficacy in improving the condition of subjects with moderate to severe genital psoriasis.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Ability to understand the purpose and risks of the trial, willingness and ability to comply with the protocol, and provide written informed consent in accordance with institutional and regulatory guidelines
Age ≥18 years of age at the time of signing consent
Diagnosis of moderate to severe psoriasis of the genital area at Screening and baseline defined as modified sPGA-G score of ≥3.
Presence of non-genital plaque psoriasis (BSA ≥1 %) at both Screening and Baseline.
Presence of psoriasis of the genital area that is inadequately controlled with topical therapy or the subject is intolerant to topical therapy
Negative evaluation for TB within 4 weeks before initiating IMP, defined as a negative QuantiFERON test. Subjects with a positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests are allowed if they have all of the following: • no history of active tuberculosis (TB) or symptoms of TB, • a posteroanterior chest radiograph (with associated report available at the site) performed within 3 months of Screening with no evidence of active TB (or of any other pulmonary infectious diseases), • if prior latent TB infection, must have history of adequate prophylaxis (per local standard of care), • if presence of latent TB is established, then treatment according to local country guidelines must have been followed for 4 weeks, prior to dosing in the study at Visit 2 (Week 0). A maximum of 2 QuantiFERON tests of no more than 3 weeks apart are allowed. A re-test is only permitted if the first is indeterminate; the result of the second test will then be used
Physical examination within normal limits or clinically acceptable limits as per the investigator prior to the first dose of study medication. The investigator is encouraged to consult with the medical monitor (or appropriate designee) if there are questions regarding the significance of any out of range values.
For women of childbearing potential, a negative serum pregnancy test at Screening and a negative urine pregnancy test within 24 hours prior to the first dose of study medication
Subject must be in good health (except for psoriasis) as judged by the investigator, based on medical history, physical examination, clinical laboratories, and urinalysis.

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Exclusion Criteria

Predominantly non-plaque forms of psoriasis specifically erythrodermic psoriasis, predominantly pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new-onset guttate psoriasis.
Live viral or bacterial vaccination within 4 weeks prior to baseline, or planned live viral or bacterial vaccination during the trial
Any significant organ dysfunction within 6 months prior to Screening that in the judgement of the Investigator places the subject at unacceptable risk for participation in a trial of an immunomodulatory agent
History of alcohol or drug abuse in the previous year in the opinion of the Investigator.
Known sensitivity to any of the products or any excipients to be administered during dosing (e.g. histidine, polysorbate 80, and sucrose).
Prior use of following therapies for treatment of psoriasis/psoriatic arthritis: a) Prior use of any investigational or approved drugs within 30 days or 5 half-lives, whichever is longer, prior to randomization. Prior use of Apremilast or other approved or investigational Janus kinase (JAK) inhibitors for the treatment of psoriatic arthritis and/or psoriasis which are not identified as permitted therapies within 5 half-lives or 15 days (whichever is longer) prior to IMP initiation. b) Use of etanercept within 4 weeks, infliximab within 8 weeks, and all other anti-TNF therapy within 3 months prior to IMP initiation c) Topical therapy within 2 weeks of randomization [including but not limited to topical Phosphodiesterase-4 enzyme (PDE-4) inhibitors (e.g. roflumilast, crisaborole) topical corticosteroids, topical retinoid or vitamin D analog preparations, tacrolimus, pimecrolimus, or anthralin/dithranol for body lesions; coal tar, salicylic acid preparations, or medicated shampoos for scalp lesions]. d) Conventional systemic therapy for psoriasis within 4 weeks prior to randomization (including but not limited to cyclosporine, corticosteroids, methotrexate, oral retinoids, mycophenolate, thioguanine, hydroxyurea, sirolimus, sulfasalazine, azathioprine, or fumaric acid esters). e) Leflunomide within 6 months prior to randomization. f) Phototherapy treatment of body within 4 weeks prior to randomization (i.e., ultraviolet B, psoralen and ultraviolet A radiation). g) Any prior use of biologics, approved or investigational, such as secukinumab, ustekinumab, ixekizumab, brodalumab, or any drugs targeting interleukin (IL)-17, IL-23, or the IL-12/IL- 23-shared p40 molecule or any biosimilars for each for the treatment of psoriasis, psoriatic arthritis, or any other indication that could impact the assessment of psoriasis h) Prior use of B-cell depleting agent or T-cell inhibitor within 12 months of Screening
Currently enrolled in any investigational study
Planned surgical intervention between baseline and the Week 16 evaluation for a pre-treatment condition.
Active infection or history of infections as follows: a. any active infection (bacterial, fungal or viral) 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, b. 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, c. recurrent or chronic infections, e.g., chronic pyelonephritis, chronic osteomyelitis, bronchiectasis, or other active infection that, in the opinion of the Investigator, might cause participation in this study to be detrimental to the subject
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 jeopardize subject safety or compliance with the protocol.
Myocardial infarction, unstable angina pectoris, or ischemic stroke within the past 6 months prior to the first IMP dose.
Women of childbearing potential who are pregnant, intend to become pregnant during the trial or within 17 weeks of completing the trial, or are lactating.
Positive human immunodeficiency virus (HIV) test result, hepatitis B virus (HBV), or hepatitis C virus (HCV) testing The following algorithm shall be followed for all subjects to evaluate this exclusion criteria: a. Subjects with positive anti-HIV antibody shall be excluded from the study b. Subjects with a Hepatitis B surface antigen (HBsAg) positive test will be excluded from the study. c. Subjects with a HBsAg negative test shall be tested for Hepatitis B core antibody (Anti-HBc). Subjects with negative Anti-HBc can be included in the study. Subjects with positive Anti-HBc shall further be tested for HBV - deoxyribonucleic acid (HBV-DNA). Subjects testing negative for HBV-DNA shall be included in the study. Subjects testing positive for HBV-DNA shall be excluded from the study. In the event the HBV-DNA test cannot be performed, the subject shall NOT be considered eligible for this study. d. Subjects with HCV antibody non-reactive will be included in the study. Subjects with HCV antibody reactive, shall be tested for HCV - ribonucleic acid (HCV RNA). If tested negative, subject can be included in the study. Subjects with HCV-RNA positive shall be excluded from the study. In the event the HCV-RNA test cannot be performed, the subject shall NOT be considered eligible for this study.
Any active malignancy (including but not limited to cutaneous basal cell carcinoma, squamous cell carcinoma or melanoma).
Any prior malignancy within 5 years from Screening (excluding successfully treated and cured cutaneous basal cell carcinoma or squamous cell carcinoma, or in situ breast ductal carcinoma).
Laboratory abnormalities at Screening, including any of the following: • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 2 times the upper limit of normal (ULN), • Creatinine ≥ 2 times the ULN • Serum direct bilirubin ≥ 1.5 mg/dl • White blood cell (WBC) count < 3.0 x 103/μL • Platelet count ≤ 100,000/µl • Hemoglobin (Hb) < 10.0 g/dl • Any other laboratory abnormality, that is considered clinically significant by the Investigator and which, in the opinion of the Investigator, will prevent the subject from completing the study or will interfere with the interpretation of the study results
Significant risk of suicidality at the Screening assessment based on the Investigator’s judgment or, if appropriate, as indicated by: a response of “yes” within the last 6 months to question 4 or 5 in the suicidal ideation section, or any response in the behavioral section of C-SSRS
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 17 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 for those women with no menses for less than 1 year.
Previous enrollment (randomized and received IMP) in this study.
Subject has evidence of skin conditions that would interfere with clinical assessments.
Subject has prolonged sun exposure or use of tanning booths or other ultraviolet light sources
Presence of excessive hair, tattoos, pigmentation, extensive scarring, pigmented lesions, or sunburn in the treatment area, which could make the affected plaque psoriasis BSA difficult to visualize
Subjects who are related to or dependent on the Investigator, Sponsor, or study site such that a conflict of interest could arise