| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10037153 |
| E.1.2 | Term | Psoriasis |
| E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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| 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 |
| - To evaluate the efficacy and safety of guselkumab in pediatric participants aged ≥6 through <18 years with chronic plaque psoriasis. |
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| E.2.2 | Secondary objectives of the trial |
- To evaluate the PK and immunogenicity of guselkumab in pediatric participants aged ≥6 through <18 years with chronic plaque psoriasis.
- To evaluate the effect of guselkumab on the dermatologic health-related quality of life in pediatric participants aged ≥6 through <18 years with chronic plaque psoriasis.
- To evaluate maintenance of response in participants who have active treatment withdrawn.
- To evaluate the efficacy and safety of retreatment with guselkumab.
- To generate clinical usability data and use experience with the VarioJect presentation (PFS-V) in pediatric participants with chronic plaque psoriasis and a body weight <70 kg. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Participant must be a boy or girl ≥6 to <18 years of age.
2. Have a diagnosis of chronic plaque-type psoriasis for at least 6 months , prior to first administration of study intervention, defined as having at screening and baseline:
• Investigator’s Global Assessment (IGA) ≥3 and
• Psoriasis Area and Severity Index (PASI) ≥12 and
• ≥10% Body Surface Area (BSA) involvement and
at least one of the following:
- very thick lesions or
- clinically relevant facial, genital, or hand/ foot involvement or
- PASI ≥20 or
- >20% BSA involvement or
- IGA=4
3. Be a candidate for phototherapy or systemic treatment of plaque psoriasis
4. Have plaque psoriasis considered by the investigator as inadequately controlled with phototherapy and/or topical therapy after an adequate dose and duration of therapy.
5. Be considered, in the opinion of the investigator, a suitable candidate for etanercept (ENBREL) therapy according to their country's approved ENBREL product labeling.
6. Be otherwise healthy on the basis of physical examination, medical history, and vital signs performed at screening. Any abnormalities, must be consistent with the underlying illness in the study population and this determination must be recorded in the participant's source documents and initialed by the investigator.
7. Contraceptive use by boys or girls should be consistent with local regulations regarding the use of contraceptive methods for those participating in clinical studies.
Before randomization, a girl must be either:
a. Not of childbearing potential defined as:
- premenarchal. A premenarchal state is one in which menarche has not yet occurred.
- permanently sterile Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy.
- or otherwise be incapable of pregnancy.
b. Of childbearing potential and practicing a highly effective method of contraception and agrees to remain on a highly effective method while receiving study intervention and until 12 weeks after last dose - the end of relevant systemic exposure.
8. A girl must agree not to donate eggs for the purposes of assisted reproduction during the study and for a period of at least 12 weeks following the last dose of study intervention.
9. A girl of childbearing potential must have a negative urine pregnancy test at screening and at all visits when study intervention is to be administered.
10. A boy who is sexually active with a female of childbearing potential and who has not had a vasectomy must agree to use a barrier method of birth control or a partner with an occlusive cap, during the study and for at least 12 weeks after receiving the last administration of study intervention. All boys must also agree to not donate sperm during the study and for at least 12 weeks after receiving the last administration of study intervention.
11. Criterion modified per Amendment 4.
11.1. Are considered eligible according to the following TB screening criteria:
• Have no history of latent or active TB before screening.
• Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
• Have had no recent close contact with a person with active TB.
• Within 10 weeks before the first administration of study intervention, have a negative QuantiFERON®-TB Gold test result. Within 10 weeks before the first administration of study intervention, a negative tuberculin skin test is additionally required if the QuantiFERON-TB Gold test is not approved/registered in that country or the tuberculin skin test is mandated by local health authorities.
Please refer to pages 34-38 of the protocol or the complete overview of the inclusion criteria |
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| E.4 | Principal exclusion criteria |
Medical history-related exclusion criteria:
1. Currently has nonplaque forms of psoriasis
2. Has current drug-induced psoriasis
3. Is pregnant, nursing, or planning a pregnancy or fathering a child while enrolled in the study or within 12 weeks after receiving the last administration of study intervention.
4. Has a history of or current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease.
5. Has a transplanted organ
6. Has had major surgery within 8 weeks before screening, or will not have fully recovered from such surgery, or has such surgery planned during the time the participant is expected to participate in the study.
7. Has unstable suicidal ideation or suicidal behavior:
• Participants ≥12 to <18 years of age may not be randomized if they have:
- a Columbia-Suicide Severity Rating Scale rating at screening of: suicidal ideation with intention to act suicidal ideation with specific plan and intent or non-suicidal self-injurious behavior within the past 6 months, OR
- a C-SSRS rating at screening of suicidal behavior
• Participants ≥6 to <12 years of age may not be randomized if they have:
- a C-SSRS rating at screening of: suicidal ideation with intention to act suicidal ideation with specific plan and intent r suicidal behavior or any self-injurious behavior ever
• Participants with a C-SSRS rating at screening of Wish to be Dead (“Ideation level 1”), Non-Specific Active Suicidal Thoughts or Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act may not be randomized if:
- participants ≥12 to <18 years of age have one of the above C-SSRS ratings within the past 6 months and are determined to be at risk by the investigator after being discussed with the medical monitor or designee.
- participants ≥6 to <12 years of age have one of the above C-SSRS ratings ever (lifetime) and are determined to be at risk by the investigator after being discussed with the medical monitor or designee.
8. Is known to have had a substance abuse problem within the previous 12 months.
Medical therapies-related exclusion criteria:
9. Has previously received guselkumab or etanercept.
10. Has any contraindications to the use of etanercept per local prescribing information.
11. Has received any anti-TNFα biologic therapy within the previous 3 months before the first administration of study intervention.
12. Is not a suitable candidate for anti-TNFα therapy for the following reasons:
• Has a history of known demyelinating diseases such as multiple sclerosis or optic neuritis.
• Has known or suspected intolerance or hypersensitivity to anti-TNFα medications (eg, clinical lupus-like syndrome, serum sickness-like reaction).
• Has a history of, or concurrent congestive heart failure (CHF), including medically controlled CHF.
13. Has received any therapeutic agent directly targeted to IL-12/23, IL-17, or IL-23 within 6 months of the first administration of study intervention (including but not limited to ustekinumab, tildrakizumab, secukinumab, ixekizumab, risankizumab, or brodalumab).
14. Has received natalizumab, efalizumab, or agents that deplete B or T cells within 12 months of screening, or, if after receiving these agents, evidence is available at screening of persistent depletion of the targeted lymphocyte population.
Please refer to pages 38-42 of the protocol for the complete overview of the exclusion criteria |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The co-primary endpoints include:
1. The proportion of participants achieving an IGA score of cleared (0) or minimal (1) at Week 16.
2. The proportion of participants with a PASI 75 response at Week 16. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- Major Secondary Endpoints for Part 1 of the study:
1. The proportion of participants achieving a PASI 90 response at Week 16.
2. The proportion of participants achieving an IGA score of cleared (0) at Week 16.
3. The change from baseline in CDLQI at Week 16.
4. The proportion of participants achieving a PASI 100 response at Week 16.
Other Secondary Endpoints for Part 1 of the study include:
5. The proportion of retreated participants that achieve a PASI 90 response over time after retreatment.
6. The proportion of retreated participants that achieve PASI responses (PASI 50, 75, 90, and 100) or IGA responses (IGA of cleared [0], minimal [1], or mild [2], IGA of cleared [0] or minimal [1], and IGA of cleared [0]) over time after retreatment.
7. The time to loss of 50% of the Week 16 PASI improvement (ie, time to retreatment) after withdrawal.
8. The time to loss of PASI 90 response after withdrawal.
9. The proportion of participants achieving a PASI 50 response at Week 16.
10. The proportion of participants who achieve an IGA score of mild or better (≤2) at Week 16.
11. The percent improvement from baseline in PASI over time through Week 16.
12. The proportion of PASI responses (PASI 50, 75, 90, and 100) over time through Week 16.
13. The proportion of IGA responses (IGA of cleared [0], minimal [1], or mild [2], IGA of cleared [0] or minimal [1], and IGA of cleared [0]) over time through Week 16.
14. The proportion of participants with CDLQI=0 or 1 at Week 16 among randomized participants with a baseline CDLQI>1.
15. The proportion of participants with Family Dermatology Life Quality Index (FDLQI)=0 or 1 at Week 16 among randomized participants with a baseline FDLQI>1.
16. The change from baseline in FDLQI at Week 16.
Secondary Endpoints for Part 2 of the study:
PASI responses, IGA responses, PASI percent improvement, change from baseline in CDLQI and FDLQI, the proportion of participants achieving a CDLQI of 0 or 1, and the proportion of participants achieving a FDLQI of 0 or 1 will be summarized over time through Week 52.
18. In addition, efficacy in the long-term extension (LTE) period for participants who continue in the LTE of the study will be summarized. |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1,2,3,4. At Week 16
5,6,7,8. At Week 52
9,10. At Week 16
11,12,13. At Week 0,4,8,12 and 16
14,15. At Week 16
16. At Baseline and at week 16
17. For PASI and IGA responses: At week 20,24,28,32,36,40,44,48 and 52; For CDLQI and FDLQI: At baseline and at week 28,36,48,52;
18. Week 60 Through Study Completion/Termination |
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| 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 | Yes |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
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| 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) | No |
| 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 | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| In Part 1 of the study, treatment for participants randomized to guselkumab or placebo will be blind |
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| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
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| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
Will this trial be conducted at a single site globally?
| No |
| E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
| Australia |
| Brazil |
| Canada |
| Russian Federation |
| United States |
| Belgium |
| Germany |
| Hungary |
| Italy |
| Poland |
| Netherlands |
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| 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
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| E.8.9 Initial estimate of the duration of the trial |
| 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 | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 25 |
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