Efficacy, Safety, and Pharmacokinetics of Tildrakizumab and Etanercept in Pediatric Patients with Moderate to Severe Chronic Plaque Psoriasis
- Trial ID
- 2023-504447-14-00
- Protocol
- TILD-19-12
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to **characterize the pharmacokinetics (PK)** and safety profile of **tildrakizumab** in pediatric subjects aged 6 to under 18 years with moderate to severe chronic plaque psoriasis over a 16-week treatment period. This is crucial for determining the appropriate pediatric dosing regimen, ensuring both efficacy and safety in this population.
Secondary objectives include evaluating the efficacy of tildrakizumab in the same pediatric cohort. This will be measured by the proportion of subjects achieving at least a 75% improvement in the **Psoriasis Area & Severity Index (PASI 75)** from baseline, and the proportion of subjects with a **Physician’s Global Assessment (PGA)** score of "clear" or "minimal" with at least a 2-grade reduction from baseline at Week 12, compared to placebo. These measures are clinically relevant as they provide insight into the therapeutic potential of tildrakizumab in improving the severity and extent of psoriasis in children and adolescents.
Participants
The clinical trial involves a total of **24 participants** who are pediatric subjects aged between **6 to 17 years**. The study population includes both male and female subjects diagnosed with moderate to severe **chronic plaque psoriasis**. Participants were selected based on specific inclusion criteria, including a diagnosis of predominantly plaque psoriasis for at least six months and a moderate to severe condition at baseline, defined by at least 10% body surface area involvement, a Physician's Global Assessment score of 3 or higher, and a Psoriasis Area and Severity Index score of 12 or higher. Subjects must weigh more than 15 kg at screening and have results of a physical examination within normal or clinically acceptable limits. The trial population is considered vulnerable, and subjects are required to have a negative evaluation for tuberculosis and up-to-date vaccination status. Lifestyle considerations such as diet and physical activity are not specified in the available data. The trial aims to evaluate the pharmacokinetics, safety, and efficacy of tildrakizumab in this pediatric population over a 16-week treatment period.
Plans and Procedures
The clinical trial is designed to evaluate the **efficacy**, safety, and pharmacokinetics of **Tildrakizumab** in pediatric subjects aged 6 to under 18 years with moderate to severe chronic plaque psoriasis. This is a multicenter, randomized, placebo, and active comparator-controlled trial. The study is structured into multiple parts, with a primary focus on characterizing the pharmacokinetic parameters and assessing the efficacy of Tildrakizumab over a 16-week treatment period. The trial aims to achieve at least a 75% improvement in the Psoriasis Area & Severity Index (PASI75) and a Physician’s Global Assessment (PGA) score of "clear" or "minimal" with a minimum 2-grade reduction from baseline at Week 16 compared to placebo.
The trial is expected to run from April 2020 to April 2025, with participant involvement lasting up to 60 weeks. The study includes an initial screening visit to confirm eligibility based on criteria such as age, weight, and disease severity. Participants will undergo regular follow-up visits to monitor safety, efficacy, and pharmacokinetic parameters. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any post-study care is arranged.
Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with the study protocol, or if the investigator deems it necessary for the participant's safety. The trial employs a double-blind design to ensure unbiased results, with participants randomly assigned to receive either Tildrakizumab, a matching placebo, or an active comparator, Enbrel. The study's rigorous methodology and comprehensive design aim to provide valuable insights into the treatment of pediatric chronic plaque psoriasis.
Treatment
The clinical trial involves the administration of **Tildrakizumab**, a **solution for injection** formulated for **subcutaneous use**. Tildrakizumab is a biological product of biotechnological origin, specifically a protein, and is provided by Sun Pharmaceutical Industries. The trial is designed to evaluate the pharmacokinetics, safety, and efficacy of Tildrakizumab in pediatric subjects aged 6 to less than 18 years with moderate to severe chronic plaque psoriasis. The dosing regimen is based on a milligram per kilogram (mg/kg) basis, with a maximum treatment period of 60 weeks. The trial aims to determine the appropriate pediatric dose by monitoring the subjects' response over a 16-week treatment period.
In addition to the experimental medication, the trial includes a **comparator treatment** using **Enbrel 25 mg powder for solution for injection**, which is also administered via **subcutaneous use**. Enbrel, containing the active substance **etanercept**, is a biological product of biotechnological origin provided by Pfizer Europe MA EEIG. The maximum daily dose for Enbrel is 50 mg, with a total maximum dose of 600 mg over a 15-week period. This comparator treatment serves to evaluate the relative efficacy and safety of Tildrakizumab against an established treatment for chronic plaque psoriasis.
The trial also incorporates a **placebo** control, specifically a **Tildrakizumab matching placebo**, to further assess the efficacy of the experimental treatment. The placebo is designed to match the pharmaceutical form and administration route of Tildrakizumab, ensuring blinding and minimizing bias in the trial outcomes. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol and to accurately assess the therapeutic effects of the investigational and comparator treatments.
Efficacy
The efficacy of Tildrakizumab in pediatric subjects with moderate to severe chronic plaque psoriasis will be assessed through specific endpoints. The primary efficacy endpoints include the proportion of subjects achieving at least a 75% improvement in the Psoriasis Area & Severity Index (PASI75) from baseline at Week 16, and the proportion of subjects with a Physician’s Global Assessment (PGA) score of "clear" or "minimal" with at least a 2-grade reduction from baseline at Week 16. These endpoints will be measured and collected at the specified timepoint of Week 16, using validated scales for PASI and PGA assessments. The analysis will focus on comparing the efficacy of Tildrakizumab against placebo in achieving these clinical improvements in the pediatric population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Parts A and B A subject must have met all the criteria listed below to participate in the study. - Subject must be 6 to ≤ 17 years of age, of either sex, of any race/ ethnicity, must weigh > 15 kg at screening
- -Subject has a negative evaluation for tuberculosis (TB) within 4 weeks before initiating Investigational medicinal product (IMP), defined as a negative QuantiFERON test. Subjects with a positive or 2 successive indeterminate QuantiFERON tests are allowed if they have all of the following: - No history of active TB or symptoms of TB - A posterior-anterior (PA) chest radiogram (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 inclusion in the study. A maximum of 2 QuantiFERON tests are allowed. A re-test is only permitted if the first is indeterminate; the result of the second test will then be used.
- -Subject should have documentation of adequate, up-to-date, age-appropriate vaccination status at screening. If required, antibody titers may be checked at screening based on investigator’s discretion.
- -Subject is unlikely to conceive, as indicated by at least one yes answer to the following questions: - Subject is a male. - Subject is a female of child-bearing potential and agrees to abstain from heterosexual activity OR use a medically accepted method of contraception OR use appropriate effective contraception as per local regulations or guidelines for continued use during the study and for 6 months following administration of the last dose of the investigational medicinal product. Medically accepted methods of contraception include, but are not limited to, condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed Intra uterine Device (IUD), inert or copper-containing IUD, hormone-releasing IUD, systemic hormonal contraceptive, and surgical sterilization (e.g., hysterectomy or tubal ligation). 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). - Subject is a surgically sterilized female or is documented to be pre- menarchal
- -For a female with 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 and at all subsequent visits as per the schedule of assessments.
- − Subject is unlikely to conceive, as indicated by at least one “yes” answer to the following questions: - Subject is male - Subject is a female of child-bearing potential and agrees to abstain from heterosexual activity OR use a medically accepted method of contraception OR use appropriate effective contraception as per local regulations or guidelines for continued use during the study and for 6 months following administration of the last dose of the investigational medicinal product. Medically accepted methods of contraception include, but are not limited to, condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed Intra uterine Device (IUD), inert or copper-containing IUD, hormone-releasing IUD, systemic hormonal contraceptive, and surgical sterilization (e.g., hysterectomy or tubal ligation). Male subjects with female partners of childbearing potential who are not using birth control as described above must use a barrier method of contraception (eg, condom) if not surgically sterile (ie, vasectomy). - Subject is a surgically sterilized female or is documented to be pre-menarchal
- − For a woman of childbearing potential, negative urine pregnancy test within 24 hours prior to the first dose of study medication for the extension study and at each subsequent visit
- − Subject must have results of clinical laboratory tests (complete blood count [CBC], blood chemistries, and urinalysis) within normal limits or clinically acceptable to the investigator prior to the first dose of study medication. Note: 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.
- − Subject must have results of a physical examination, including blood pressure within clinically acceptable limits to the investigator prior to the extension study's first dose of study medication for the extension study Note: 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.
- Subject must have results of a physical examination within normal limits or clinically acceptable limits to 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. Laboratory abnormalities deemed not clinically significant by the investigator should be clarified with the Contract Research Organization (CRO) or Sponsor’s Medical monitor (MM) before proceeding with the trial.
- PART C: − Willingness and ability to comply with the protocol.
- − Subject has completed at least 64 weeks of Part B of the study. Subjects rolled over from Part A to Part B to receive open label tildrakizumab and subjects initially randomized to Etanercept and receiving open label tildrakizumab in Part B, can enter LTE from Week 52 onwards.
- − Subject has PGA score of ≤ 2 at the baseline visit of Part C.
- To participate in whole-body photography at designated sites, the subject must be willing to give assent or written informed consent and be able to adhere to dose and visit schedules. Photography will be an optional procedure for subjects to participate in the trial. Note: Whole-body photographs are being used for visual evaluation only and will not be included in any analyses. A subject unwilling to consent to any of this procedure may still be included in this trial; however, whole-body photography must not be obtained. Photography will not be applicable to Part A.
- Diagnosis of predominantly plaque psoriasis for ≥6 months (as determined by subject interview and confirmation of diagnosis through physical examination by investigator).
- Moderate to severe psoriasis at baseline defined as : - At least 10% body surface area (BSA) involvement - PGA score ≥ 3 - PASI score ≥ 12
- -Subject must be considered a candidate for systemic therapy and/or phototherapy
- Willingness and ability to comply with the protocol
Exclusion Criteria
- PART A and B - A subject meeting any of the exclusion criteria listed below must be excluded from participating in the trial: - Subject has predominantly non-plaque forms of psoriasis, specifically erythrodermic psoriasis, predominantly pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new-onset guttate psoriasis.
- Subject with presence of any infection or history of recurrent infection requiring treatment with systemic antibiotics within 2 weeks prior to screening, or severe infection (e.g., pneumonia, cellulitis, bone or joint infections) requiring hospitalization or treatment with IV antibiotics within 8 weeks prior to Screening
- Subject with any previous use of tildrakizumab or other IL-23/Th-17 pathway inhibitors, including p40, p19 and IL-17 antagonists for psoriasis.
- Subject who has received live viral or bacterial vaccination within 4 weeks prior to baseline or who intends to receive live viral or bacterial vaccination during the trial. Note: If needed, an entry into the study could be deferred until such vaccination is completed and adequate time (4 weeks) has elapsed until baseline.
- Prior use of TNF-alpha inhibitors will be allowed. However, the number of subjects with prior use of TNF-alpha inhibitors will be capped at 40% and the analysis will be stratified based on prior use of these biologics. When the number of subjects with prior use of TNF –alpha inhibitors reaches 40% of the sample size, the study population will be re-evaluated with respect to the general psoriasis population, and % cap may be revised if found necessary.
- Positive human immunodeficiency virus (HIV) test result, hepatitis B virus (HBV) test, or hepatitis C virus (HCV) test result.
- Prior malignancy or concurrent malignancy (excluding successfully treated basal cell carcinoma, squamous cell carcinoma of the skin in situ, squamous cell carcinoma with no evidence of recurrence within 5 years or carcinoma in situ of the cervix that has been adequately treated).
- PART C: - A subject meeting any of the exclusion criteria listed below must be excluded from participating in the extension study: - Females of childbearing potential, who are pregnant or intend to become pregnant (within 6 months following administration of the last dose of the investigational medicinal product), or are lactating (Sexually active adolescent girls will be required to use contraception).
- Subject who intends to receive live viral or bacterial vaccination during the trial.
- Subject has any active or uncontrolled significant organ dysfunctionor clinically significant laboratory abnormalities or any condition that place, the subject at unacceptable risk for participation in a long-term trial of immunomodulatory therapy in the judgment of the Investigator.
- Subject who, in the opinion of the investigator, will not be able to participate optimally in the trial.
- Subjects who have a high 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 12 months to Questions 4 or 5 in the suicidal ideation section, or any positive response in the behavioral section of the C-SSRS
- Subject is receiving or is anticipated to receive any of the prohibited medications, supplements, and other substances listed in Table 4 during the course of the trial
- Subject who is currently participating in another interventional clinical trial or has participated in an interventional clinical trial within 5 half-lives (of the drug) to wash out prior to randomization. (Subjects participating in observational studies or non-interventional registry studies may be included in the study)
- Subject has sustained, uncontrolled hypertension (defined as average SBP and/or DBP that is greater than or equal to the 95th percentile for sex, age, and height on three or more occasions.), or has uncontrolled diabetes.
- Subject has been hospitalized due to an acute cardiovascular event, illness or surgery within 6 months prior to screening
- Within 6 months prior to screening, any significant organ dysfunction or clinically significant laboratory abnormalities that place the subject at unacceptable risk for participation in a trial of immunomodulatory therapy are in the judgment of the investigator.
- The subject or a family member is among the personnel of the investigational site or sponsor/designee staff directly involved with this trial.
- Any concomitant medical condition that in the opinion of the Investigator could affect the trial outcome or present an unacceptable risk
- Subject who, in the opinion of the Investigator, will not be a reliable participant in the trial.
- Subject who has a history of alcohol or drug abuse in the previous year.
- Subject has laboratory abnormalities at screening, including any of the following: a) Alanine transaminase (ALT) or aspartate transaminase (AST) ≥2X the upper limit of normal b) Creatinine ≥1.5X the upper limit of normal c) Serum direct bilirubin ≥ 1.5 mg/dL d) White blood cell count < 3.0 x 103/μL e) Any other laboratory abnormality 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.
- Subjects with a history of psychiatric inpatient hospitalization within the past year
- Subjects with any other clinically significant laboratory abnormality, 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
- History of hypersensitivity to the applicable IMP: tildrakizumab, etanercept (EU) or any ingredients of the study drug or placebo
- Subject who is expected to require topical therapy, phototherapy, or additional systemic therapy for psoriasis during the trial.
- Female subjects of childbearing potential who are pregnant or intend to become pregnant (within 6 months following administration of the last dose of the investigational medicinal product) or are lactating (Sexually active adolescent girls will be required to use contraception)
- History of hypersensitivity to tildrakizumab or any excipients
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Hungary | Recruiting | 01 Apr 2020 | 4 |
 Poland | Recruiting | 01 Apr 2020 | 98 |
 Slovakia | Recruiting | 01 Apr 2020 | 2 |
 Spain | Not Recruiting | 01 Apr 2020 | 1 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Tildrakizumab | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 0 | 60 | PRD10342802 |
Enbrel 25 mg powder for solution for injection | Comparator | POWDER FOR SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 50 | 15 | PRD6538814 |
Tildrakizumab matching placebo | Placebo | N/A | — | — | — | N/A |