| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| moderate to severe chronic plaque psoriasis |
|
| E.1.1.1 | Medical condition in easily understood language |
| chronic inflammatory skin disease |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Part A: Dose finding Component
To characterize PK and safety of tildrakizumab in pediatric subjects during a 16-week treatment period in support of final pediatric dose selection.
Part B: Randomized Trial Component
To evaluate the efficacy of tildrakizumab in pediatric subjects from 6 to <18 years of age with moderate to severe chronic plaque psoriasis as measured by the proportion of subjects with at least 75% improvement in the Psoriasis Area & Severity Index (PASI 75) response from baseline, and the proportion of subjects with Physician’s Global Assessment (PGA) score of “clear” or “minimal” with at least a 2 grade reduction from baseline at Week 16 compared to placebo. |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of tildrakizumab in pediatric subjects from 6 to
<18 years of age with moderate to severe chronic plaque psoriasis as
measured by the proportion of subjects with at least 75% improvement
in the Psoriasis Area & Severity Index (PASI 75) response) from
baseline, and the proportion of subjects with 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. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Part A&B
-Subject must be 6 to ≤17, of either sex, of any race/ ethnicity
-Must weigh >15 Kg at screening
-Diagnosis of predominantly plaque psoriasis for ≥6 mths
Moderate to severe psoriasis at baseline defined as:
-At least 10% body surface area involvement
-PGA score ≥3
-PASI score ≥12
-Subject must be considered a candidate for systemic therapy &/or phototherapy
Subject has a negative evaluation for tuberculosis within 4 wks before initiating 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
−A posterior-anterior chest radiogram performed within 3 mths of Screening with no evidence of active TB
−If prior latent TB infection must have history of adequate prophylaxis
−If presence of latent TB is established then treatment according to local country guidelines must have been followed for 4 wks prior to inclusion in the study
A max of 2 QuantiFERON tests. A retest is only permitted if the 1st is indeterminate; the result of the 2nd test will then be used
-Subject should have documentation of adequate, up-to-date, age-appropriate vaccination status at screening. Antibody titers may be checked at screening based on investigators discretion
- Subject is unlikely to conceive as indicated by at least 1 yes answer to the following questions:
- Subject is a male
- Subject is a female of child-bearing potential & 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, condoms with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed IUD, inert or copper-containing IUD, hormone-releasing IUD, systemic hormonal contraceptive, and surgical sterilization. Male subjects with female partners of childbearing potential who are not using birth control must use a barrier method of contraception if not surgically sterile
- Subject is a surgically sterilized female or is documented to be premenarchal
- For a female with childbearing potential a negative serum pregnancy test at Screening & a negative urine pregnancy test within 24 h prior to the 1st dose of study medication & at all subsequent visits as per schedule of assessment
- Subject must have results of a physical examination within normal limits or clinically acceptable limits to the investigator prior to the 1st dose of study medication. The investigator is encouraged to consult with the medical monitor 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 CRO or Sponsor MM
−To participate in whole body photography at designated sites the subject must be willing to give assent/written informed consent and be able to adhere to dose/visit schedules. Photography will be an optional procedure for subjects to participate in. Photography will not be applicable to Part A.
Part C:
−Willingness & 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 Tildra & subjects initially randomized to Etanercept & receiving open label Tildra in Part B, can enter LTE from week 52
−Subject has PGA score of ≤2 at the baseline visit of Part C
−Subject is unlikely to conceive, as indicated by at least 1 "yes" answer to the following questions:
a Subject is male
b Subject is a female of child-bearing potential & 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 with or without a spermicidal agent diaphragm or cervical cap with spermicide, medically prescribed IUD inert or copper-containing IUD hormone-releasing IUD systemic hormonal contraceptive & surgical sterilization Male subjects with female partners of childbearing potential who are not using birth control must use a barrier method of contraception if not surgically sterile
c Subject is a surgically sterilized female or is documented to be
premenarchal
Please refer to protocol for complete list |
|
| E.4 | Principal exclusion criteria |
- 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 has laboratory abnormalities at screening including any of the following:
a) Alanine transaminase or aspartate transaminase ≥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
- 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, intend to become pregnant (within following administration of the last dose of the investigational medicinal product) or are lactating
- 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 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. When the number of subjects with prior use of TNF –alpha inhibitors reach 40% of sample size, study population will be reevaluated with respect to general psoriasis population and % cap may be revised, if found necessary
- Positive human immunodeficiency virus test result, hepatitis B surface antigen, or hepatitis C virus test result
- Prior malignancy or concurrent malignancy
- 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, entry in to the study could be deferred until such vaccination is completed and adequate time has elapsed until baseline
- Subject who is currently participating in another interventional clinical trial or has participated in an interventional clinical trial within 5 halflives to wash out prior to randomization
- 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 an immunomodulatory therapy 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 which 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.
- Subjects who have high risk of suicidality at the screening assessment based on 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 who, has a history of alcohol or drug abuse in the previous year
- 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
Part C
A subject meeting any of the exclusion criteria listed below must be excluded from participating in the extension study:
1. Females of childbearing potential, who are pregnant, 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).
2. Subject who intends to receive live viral or bacterial vaccination during the trial.
Please refer to protocol for complete list of exclusion criteria |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. The proportion of subjects with at least 75% improvement in the PASI score (PASI 75 response) from baseline at Week 16.
2. The proportion of subjects with PGA score of "clear" or "minimal" with at least a 2-grade reduction from baseline at Week 16. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Key secondary end points of PASI 75 response rate and the proportion of subjects with PGA of "clear" or "minimal" with at least a 2-grade reduction from baseline at Week 12 will be analyzed using CMH test.
Other secondary efficacy endpoints of PASI 50, PASI 90, PASI 100 response rates, BSA, and CDLQI/DLQI will be summarized across all time points with descriptive statistics. For all PASI responses, a comparison between treatment groups will be analyzed using CMH test. BSA and DLQI will be analyzed between treatment groups using
continuous endpoint methods.
More detailed descriptions of these analyses will be presented in the Statistical Analysis Plan. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 13 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 22 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| India |
| United States |
| Hungary |
| Poland |
| Slovakia |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 29 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
