A Phase 3 Multicenter Randomized Double-blind Placebo-controlled Study Evaluating the Efficacy and Safety of Ustekinumab in the Treatment of Adolescent Subjects With Moderate to Severe Plaque-type Psoriasis

The primary objectives of this study are to evaluate the efficacy and safety of 2 SC dosing tiers of ustekinumab in the treatment of adolescent subjects 12 to 18 years of age with moderate to severe chronic plaque psoriasis

Data and Resources

A Phase 3 Multicenter Randomized Double-blind Placebo-controlled Study Evaluating the Efficacy and Safety of Ustekinumab in the Treatment of Adolescent Subjects With Moderate to Severe Plaque-type Psoriasisjson
The primary objectives of this study are to evaluate the efficacy and safety...
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Field	Value
Modified	2019-05-21
Release Date	2019-04-19
Identifier	04a5c8cf-e4a0-439a-a4ec-a39a143cad1e
License	License Not Specified
Public Access Level	Public

EudraCT ID

EudraCT ID
EudraCT Number	2009-014368-20
Sponsor’s protocol code number	CNTO1275PSO3006
National competent authority	Belgium - FPS Health-DGM
Clinical trial type	EEA CTA Trial Status: Completed
Trial status	Completed
Date on which this record was first entered in the eudract database	2010-04-27
Record last import	2018-02-09 14:47:18
Clinical trial registry name	EUCTR

Protocol

Protocol
Member State Concerned	Belgium - FPS Health-DGM
EudraCT Number	2009-014368-20
Full title of the project	A Phase 3 Multicenter Randomized Double-blind Placebo-controlled Study Evaluating the Efficacy and Safety of Ustekinumab in the Treatment of Adolescent Subjects With Moderate to Severe Plaque-type Psoriasis
Title of the project for lay people, in easily understood, i.e. non-technical, language	This is a study of the safety and efficacy of ustekinumab CNTO 1275 in adolescent patients with moderate to severe psoriasis
Name or abbreviated title of the project where available	CADMUS
Sponsor’s protocol code number	CNTO1275PSO3006
project is part of a Paediatric Investigation Plan	Yes
EMA Decision number of Paediatric Investigation Plan	P192009
Source type	Trials

Sponsor(s)

Primary organization that oversees implementation of study and is responsible for data analysis.
Name of organisation	Janssen-Cilag International NV
Country of organisation	Belgium
Status of organisation	Commercial

Contact point designated by the sponsor for further information on the project
Name of organisation	Janssen-Cilag International NV
Functional name of contact point	Clinical Registry Group

Address
Street Address	Archimedesweg 29
Town / City	Leiden
Post code	2333 CM
Country	Netherlands
Telephone number	31 71 524 2166
Fax number	31 71 524 2110
E-mail	clinicaltrialsEUitsjnjcom

Source(s) of Monetary or Material Support

Organisation providing support
Name of organisation	Janssen Research Development
Country of organisation	United States

General information

Medical condition or disease under investigation
Medical condition(s) being investigated	Moderate to Severe Plaque-type Psoriasis
Medical condition in easily understood language	Moderate to Severe Psoriasis

Therapeutic area
Therapeutic area	Diseases C - Immune System Diseases C20

Medical condition or disease under investigation (MedDRA Classification)
Version	141
Level	PT
Classification code	10037153
Term	Psoriasis
System Organ Class	10040785 - Skin and subcutaneous tissue disorders
Condition being studied is a rare disease	No

Objective of the project
Main objective of the project	The primary objectives of this study are to evaluate the efficacy and safety of 2 SC dosing tiers of ustekinumab in the treatment of adolescent subjects 12 to 18 years of age with moderate to severe chronic plaque psoriasis
Secondary objectives of the project	The secondary objectives of this study are to: 1 Evaluate the impact of ustekinumab on physical social emotional and academic functioning as well as dermatologic symptom impact on health-related quality of life in adolescent subjects with moderate to severe chronic plaque psoriasis 2 Evaluate the pharmacokinetics and immunogenicity of ustekinumab in adolescent subjects with moderate to severe chronic plaque psoriasis

Scope
Diagnosis	No
Prophylaxis	No
Therapy	Yes
Safety	Yes
Efficacy	Yes
Pharmacokinetic	Yes
Pharmacodynamic	No
Bioequivalence	No
Dose response	Yes
Pharmacogenetic	No
Pharmacogenomic	Yes
Pharmacoeconomic	No
Other scope	No

Design of the project

Principal inclusion and exclusion criteria
Principal inclusion criteria	Potential subjects must satisfy all of the following criteria to be enrolled in the study: Boys or girls 12 and 18 years of age Have a diagnosis of plaque-type psoriasis with or without PsA for at least 6 months prior to first administration of study agent with widespread lesions defined by PASI 12 PGA 3 and involved BSA 10 Are candidates for phototherapy or systemic treatment of psoriasis either naive or history of previous treatment or have psoriasis considered by the investigator as poorly controlled with topical therapy after an adequate dose and duration of therapy Girls must be either: Premenarchal or surgically sterile have had a hysterectomy or bilateral oophorectomy tubal ligation or otherwise be incapable of pregnancy or abstinent at the discretion of the investigatorper local regulations or if sexually active be practicing a highly effective method of birth control eg prescription oral contraceptives contraceptive injections contraceptive patch intrauterine device double-barrier method eg condoms diaphragm or cervical cap with spermicidal foam cream or gel male partner sterilization as local regulations permit before entry and must agree to continue to use the same method of contraception throughout the study and for 15 weeks after receiving the last dose of study drug All girls must have a negative urine pregnancy test at screening and a negative urine pregnancy test at Week 0 Boys must agree to use a double barrier method of birth control and to not donate sperm during the study and for 15 weeks after receiving the last dose of study drug Are considered eligible according to the following TB screening criteria: Have no history of latent or active TB prior to screening Have no signs or symptoms suggestive of active TB upon medical history andor physical examination Have had no recent close contact with a person with active TB or if there has been such contact will be referred to a physician specializing in TB to undergo additional evaluation and if warranted receive appropriate treatment for latent TB prior to or simultaneously with the first administration of study agent Within 6 weeks prior to the first administration of study agent have a negative QuantiFERON-TB Gold test result see Attachment 5 or have a newly identified positive QuantiFERON-TB Gold test result in which active TB has been ruled out and for which appropriate treatment for latent TB see Section 912 has been initiated either prior to or simultaneously with the first administration of study agent Indeterminate results should be handled as outlined in Section 912 A negative tuberculin skin test see Attachment 6 or a newly identified positive tuberculin skin test result in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of study agent is additionally required if the QuantiFERONTB Gold test is not approvedregistered in that country Must have positive antibody titers to varicella and measles prior to the first administration of study agent Must agree not to receive a live virus or live bacterial vaccination at least 6 weeks or longer as indicated in the package insert of the relevant vaccine prior to the first administration of study agent during the study or within 15 weeks after the last administration of study agent Must agree not to receive a bacille Calmette-Gurin BCG vaccination within 12 months of screening during the study or within 12 months after the last administration of study agent Must avoid prolonged sun exposure and avoid use of tanning booths or other ultraviolet light sources during study Have screening laboratory test results within the following parameters: Hemoglobin 12 gdL White blood cells 45 x 109L Neutrophils 15 x 109L Platelets 150 x 109L Serum creatinine 15 mgdL or 133 molL AST ALT and alkaline phosphatase levels must be within the 15 x ULN for the laboratory conducting the test Subjects or their legally-acceptable representatives must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study Assent is also required of children capable of understanding the nature of the study typically 7 years of age and older as described in Section 1623 Informed Consent
Principal exclusion criteria	Potential subjects who meet any of the following criteria will be excluded from participating in the study: Currently have nonplaque forms of psoriasis eg erythrodermic guttate or pustular Have current drug-induced psoriasis eg a new onset of psoriasis or an exacerbation of psoriasis from beta blockers calcium channel blockers or lithium Are pregnant nursing or planning a pregnancy or fathering a child while enrolled in the study or within 15 weeks after receiving the last administration of study agent Have used any therapeutic agent targeted at reducing IL-12 or IL-23 including but not limited to ustekinumab and briakinumab Have used topical medicationstreatments that could affect psoriasis or PASI evaluation including but not limited to corticosteroids anthralin calcipotriene topical vitamin D derivatives retinoids tazarotene methoxsalen trimethylpsoralens within 2 weeks of the first administration of study agent Have received phototherapy or any systemic medicationstreatments that could affect psoriasis or PASI evaluation including but not limited to oral or injectable corticosteroids retinoids 125 dihydroxy vitamin D3 and analogues psoralens sulfasalazine hydroxyurea or fumaric acid derivatives within 4 weeks of the first administration of study agent Have received any systemic immunosuppressants eg MTX azathioprine cyclosporine 6-thioguanine mercaptopurine mycophenolate mofetil hydroxyurea and tacrolimus within 4 weeks of the first administration of study agent Have received any biologic agent within the previous 3 months or 5 times the t12 of the agent whichever is longer Have received natalizumab efalizumab or agents that deplete B or T cells eg rituximab alemtuzumab abatacept or visilizumab within 12 months of screening or if after receiving these agents evidence is available at screening of persistent depletion of the targeted lymphocyte population Are currently receiving lithium antimalarials or IM gold or have received lithium antimalarials or IM gold within 4 weeks of the first administration of study agent Have used a topical investigational agent within 4 weeks or 5 times the t12 of the investigational agent whichever is longer before the planned start of treatment or are currently enrolled in a study of a topical agent Have used a non-topical investigational drug within 3 months or 5 times the t12 of the investigational agent whichever is longer before the planned start of treatment or are currently enrolled in a study of a non-topical investigational agent Have received or are expected to receive any live virus or bacterial vaccination at least 6 weeks or longer as indicated in the package insert of the relevant vaccine prior to the first administration of study agent during the study or within 15 weeks after the last administration of study agent Have had a BCG vaccination within 12 months of screening Have a history of chronic or recurrent infectious disease including but not limited to chronic renal infection chronic chest infection eg bronchiectasis recurrent urinary tract infection recurrent pyelonephritis or chronic nonremitting cystitis or open draining or infected skin wounds or ulcers Have or have had a serious infection eg sepsis pneumonia or pyelonephritis or have been hospitalized or received IV antibiotics for an infection during the 2 months prior to screening Have a history of latent or active granulomatous infection including histoplasmosis or coccidioidomycosis prior to screening Have had a nontuberculous mycobacterial infection within 6 months prior to screening Have ever had an opportunistic infection eg cytomegalovirus pneumocystosis aspergillosis Are known to be infected with HIV hepatitis B or hepatitis C Have a documented history of immune deficiency syndrome eg severe combined immuno deficiency syndrome T cell deficiency syndromes B cell deficiency syndromes and chronic granulomatous disease Have a known history of lymphoproliferative disease including lymphoma or signs and symptoms suggestive of possible lymphoproliferative disease such as lymphadenopathy andor splenomegaly Have 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 Have any known malignancy or have a history of malignancy Have a transplanted organ with exception of a corneal transplant 3 months prior to the first administration of study agent

End points
Primary end point(s)	The primary endpoint in this study is the proportion of subjects who achieve a PGA score of cleared or minimal at Week 12 In the primary efficacy analysis data from all randomized subjects will be analyzed according to their assigned treatment group Subjects who discontinue study treatment due to unsatisfactory therapeutic response or an AE of worsening psoriasis or who started protocol-prohibited medicationstherapies that could improve psoriasis after the baseline visit but prior to Week 12 or who enter early escape will be considered as nonresponders at Week 12 In addition subjects who have a missing PGA score at Week 12 will be considered as not achieving the primary endpoint at Week 12 In the primary analysis the proportion of subjects with a PGA score of cleared or minimal at Week 12 will be compared between the ustekinumab LD group and the placebo group and between the ustekinumab HD group and the placebo group using CMH chi-square test stratified by weight 60 kg or 60 kg The p-values will be ordered To maintain an overall Type I error rate of 005 the Holms procedure will be used Holm 1979 The smaller p-value will be compared to 0025 2-sided If this test is significant then the other p-value will be compared to 005 2 sided Otherwise both tests are considered not significant To establish the efficacy of ustekinumab compared with placebo at least 1 of the comparisons must be statistically significant ie at least the smaller p-value must be 0025
Timepoint(s) of evaluation of this end point	Week 12
Secondary end point(s)	Proportion of patients that achieve Psoriasis Area and Severity Index PASI 75 response Change from baseline in Childrens Dermatology Life Quality Index CDLQI The proportion of patients who achieve a Psoriasis Area and Severity Index PASI 90 response
Timepoint(s) of evaluation of this end point	Week 12

Trial type and phase
Human pharmacology (Phase I)	No
First administration to humans	No
Bioequivalence study	No
Other	No
Therapeutic exploratory (Phase II)	No
Therapeutic confirmatory (Phase III)	Yes
Therapeutic use (Phase IV)	No

Design of the Trial
Controlled	Yes
Randomised	Yes
Open	No
Single blind	No
Double blind	Yes
Parallel group	Yes
Cross over	No
Other	No
Comparator of controlled trial	No
Other medicinal product(s)	No
Placebo	Yes
Other	No
Number of treatment arms in the project	4

Duration of the project
Definition of the end of the project and justification where it is not the last visit of the last subject undergoing the project	End of trial is defined as last patient last visit

Initial estimate of the duration of the project
In the Member State concerned years	3
In the Member State concerned months	3
In all countries concerned by the project years	3
In all countries concerned by the project months	3

Sites involved in the project

Sites involved in the project
The project involves single site in the Member State concerned	No
The project involves multiple sites in the Member State concerned	Yes
Number of sites anticipated in Member State concerned	3
The project involves multiple Member States	Yes
Number of sites anticipated in the EEA	40
Project being conducted both within and outside the EEA	Yes
Project being conducted completely outside of the EEA	Information not present in EudraCT
If E.8.6.1 or E.8.6.2 are yes, specify the regions in which project sites are planned	Canada

Investigational Medicinal Product (IMP)

Information on Placebo
Is a Placebo used in this project?	1
Pharmaceutical form of the placebo	Solution for injection
Route of administration of the placebo	Subcutaneous use

Population

Age
Under 18	Yes
In Utero	No
Preterm newborn infants (up to gestational age < 37 weeks)	No
Newborns (0-27 days)	No
Infants and toddlers (28 days-23 months)	No
Children (2-11years)	No
Adolescents (12-17 years)	Yes
Adults (18-64 years)	No
Elderly (>=65 years)	No

Age Range
Under 18: Number of subjects	150
Adolescents (12-17 years): Number of subjects	150

Gender
Female	Yes
Male	Yes

Group of project subjects
Healthy volunteers	No
Patients	Yes
Specific vulnerable populations	Yes
Women of childbearing potential not using contraception	No
Women of child-bearing potential using contraception	Yes
Pregnant women	No
Nursing women	No
Emergency situation	No
Subjects incapable of giving consent personally	No
Others	No

Planned number of subjects to be included
In the member state	6
For a multinational project in the EEA	120
In the whole clinical project	150
Plans for treatment or care after the subject has ended the participation in the project (if it is different from the expected normal treatment of that condition)	For individual subjects participating in the CADMUS study no long term treatment is planned beyond 60 weeks This decision was primarily based on the fact that there is no safety data yet available in kids in any indication and thus it is prudent to scientifically evaluate the benefit-risk profile over approximately 1 year before ustekinumab is provided longer term

Investigator networks

Investigator networks
Network Country	2010-03-16

Review

Competent Authority
Competent Authority Decision	Authorised
Date of Competent Authority Decision	2010-04-30

Ethics Committee
Ethics Committee Opinion of the project application	Favourable

End of project

End of project
End of project Status	Completed
Date of the global end of the project	2014-01-04

Data quality

Data quality
Project has a data monitoring committee	Yes

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A Phase 3 Multicenter Randomized Double-blind Placebo-controlled Study Evaluating the Efficacy and Safety of Ustekinumab in the Treatment of Adolescent Subjects With Moderate to Severe Plaque-type Psoriasis

Data and Resources