|E.1 Medical condition or disease under investigation
|E.1.1||Medical condition(s) being investigated ||
|E.1.1.1||Medical condition in easily understood language ||
|E.1.1.2||Therapeutic area ||Diseases [C] - Skin and Connective Tissue Diseases [C17]
|E.1.2 Medical condition or disease under investigation
|E.1.2||Classification code ||10037153
|E.1.2||System Organ Class ||10040785 - Skin and subcutaneous tissue disorders
|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 ||
|The primary objective of Part 1 (Weeks 0 to 16) is to evaluate the optimal dose regimen of SCH 900222 to induce PASI 75 response at Week 16 in subjects with moderate-to-severe psoriasis.The primary objective of Part 2 (Weeks 16-52) is to evaluate the optimal dose regimen to maintain PASI 75 response at Week 52. The primary objective of Part 3 (Weeks 52-72) is to assess the duration of effect of SCH 900222 as determined by the time at which the Week 52 improvement from baseline is reduced by > 50% (ie, disease relapse). The primary safety objective is to assess the safety/tolerability of multiple-dose administration of SCH 900222.
|E.2.2||Secondary objectives of the trial ||
|Assess efficacy as defined by PASI 75 at Week 12. Assess efficacy as defined by PGA at Week 16.
|E.2.3||Trial contains a sub-study || No
|E.3||Principal inclusion criteria ||
|A subject must meet all the criteria listed below to participate in the trial.
1. Ability to understand the purpose and risks of the trial, willingness and ability
to comply with the protocol, provide written informed consent in accordance
with institutional and regulatory guidelines, and, for subjects at US sites,
authorization to use protected health information (Health Insurance Portability
and Accountability Act [HIPAA]).
2. Subject must be ≥18 years of age. A subject may be of either sex and of any
3. Diagnosis of predominantly plaque psoriasis for ≥6 months (as determined by
subject interview and confirmation of diagnosis through physical examination
4. Subject is considered to be a candidate for phototherapy or systemic therapy.
5. PASI score ≥12 at Baseline.
6. Psoriasis BSA involvement ≥10% at Baseline.
7. PGA of at least moderate disease (moderate, marked, or severe) at Baseline.
8. Subject is considered to be eligible according to the following tuberculosis
(TB) Screening criteria:
a. Has no history of untreated latent or active TB prior to Screening.
Prophylactic treatment for latent TB (as per local guidelines) must be
initiated at least 4 weeks prior to first administration of study medication.
b. Has no signs or symptoms suggestive of active TB upon medical
history and/or physical examination.
c. Has 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 medication.
d. Within 4 weeks prior to the first administration of study medication,
either has negative diagnostic TB test results (defined as a negative
tuberculin skin test or a negative QuantiFERON-TB Gold test.
e. A subject who has a positive intradermal skin test or positive
QuantiFERON gold TB test, or who has had recent close contact with
a person with active TB, or has signs or symptoms suggestive of active
TB upon medical history and/or physical examination, must have a
negative chest CT scan taken within 4 weeks of the first administration
of study medication. The scan must be read by a qualified radiologist,
and must have no evidence of current active TB or old inactive TB.
9. Subject is unlikely to conceive, as indicated by at least one “yes” answer to
the following questions:
a. Subject is a male.
b. Subject is a surgically sterilized female.
c. Subject is a postmenopausal female ≥45 years of age with >1year
since last menses.
d. Subject is a non-sterilized, premenopausal female and agrees to
abstain from heterosexual activity OR use double barrier contraception
(ie, condom with spermicide or has a vasectomized partner PLUS oral,
intramuscular or implanted contraceptives, diaphragm with spermicide,
contraceptive sponge, intrauterine device [IUD]) OR use appropriate
double barrier contraception as per local regulations or guidelines.
10. 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.
11. 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 and medical monitor (or appropriate designee)
prior to the first dose of study medication.
12. Subject must have results of a physical examination, including blood
pressure, within normal limits or clinically acceptable limits to the investigator
and medical monitor (or appropriate designee) prior to the first dose of study
13. To participate in the pharmacogenomics analysis, skin biopsies, or whole
body photography, the subject must be willing to give written informed
consent for these procedures and be able to adhere to dose and visit
schedules. Note: A subject unwilling to consent to these procedures may be
included in the trial; however, pharmacogenomic samples, skin biopsies
and/or whole body photography must not be obtained.
|E.4||Principal exclusion criteria||
|A subject meeting any of the exclusion criteria listed below must be excluded
from participating in the trial:
1. Presence of nonplaque forms of psoriasis specifically erythrodermic psoriasis,
predominantly pustular psoriasis, medication-induced or medicationexacerbated
psoriasis, or new onset guttate psoriasis.
2. Subject who will require oral or injectable corticosteroids during the trial.
3. Presence of any infection requiring treatment with systemic antibiotics within 2 weeks
prior to Screening, or serious infection (eg, pneumonia, cellulitis, bone or joint
infections) requiring hospitalization or treatment with IV antibiotics within
8 weeks prior to Screening.
4. Women of childbearing potential who are pregnant, intend to become
pregnant (within 6 months of completing the trial), or are lactating.
5. Positive human immunodeficiency virus (HIV) test result, hepatitis B surface
antigen, or hepatitis C test result.
6. Prior malignancy or concurrent malignancy (excluding successfully treated
basal cell carcinoma, squamous call carcinomaof the skin in situ, squamous call carcinoma with no evidence of recurrence within 5 years, or carcinoma in situ of the cervix that has been
7. Subject who has received live virus vaccination within 4 weeks prior to
Baseline or who intends to receive live virus vaccination during the trial.
8. Previous exposure to any agents targeting IL-12 and/or IL-23.
9. Subject with prior exposure to two or more TNF antagonists with
discontinuation due to lack of efficacy.
10. Subject who is currently participating in another interventional clinical trial or
have participated in an interventional clinical trial within 4 weeks prior to
Screening. Note: Subjects participating in observational studies or noninterventional
registry studies may be included in the study.
11. The subject or a family member is among the personnel of the investigational
or sponsor staff directly involved with this trial.
12. Within 6 months prior to Screening, any significant organ dysfunction,
including cardiac (see below), renal, liver, central nervous system, pulmonary,
vascular, gastrointestinal, endocrine, psychiatric, ophthalmologic, or
metabolic conditions 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 and sponsor.
However, if the subject has significant organ dysfunction or exceeds the
ranges below, the investigator should confer with the medical monitor (or
appropriate designee) regarding study enrollment:
a. absolute neutrophil count <1500/mm3
b. platelet count <100,000/mm3
c. hemoglobin <11 g/dL
d. creatinine ≥1.5 x the upper limit of normal (ie, ≥133 μmol/L)
e. alanine transaminase (ALT [SGPT]) or aspartate transaminase (AST
[SGOT]) ≥2.5 x the upper limit of normal
13. History of myocardial infarction, congestive heart failure (New York Heart
Association [NYHA] Class 3 or 4), uncontrolled arrhythmias, cardiac
revascularization, stroke, uncontrolled hypertension, or uncontrolled diabetes
within 6 months of Screening.
14. Subject who, in the opinion of the investigator, will not be able to participate
optimally in the trial.
15. Subject with a history of alcohol or drug abuse in the previous 2 years.
16. Subject who has received any of the medications listed below within the
indicated washout period prior to randomization:
Prohibited Medications, Supplements, and Other Substances for Entry Into the Trial
Prohibited Medications, Supplements, and Other Substances
a) Topical psoriasis treatment (excluding class VI or VII low-potency topical
corticosteroids such as prednicarbate 0.05%, triamcinolone acetonide
0.025%, fluocinolone acetonide 0.01%, desonide 0.05%, hydrocortisone
2.5% or hydrocortisone 1%)--2 weeks washout period prior to randomization
b) Conventional systemic psoriasis therapy (eg, cyclosporine, methotrexate,
acitretin, fumaric acid esters) or phototherapy (eg, UV-B light
phototherapy, Psoralen-UV therapy, tanning salon or home-administered
UVB) --4 weeks washout period prior to randomization
c) Treatment with a biological agent (including monoclonal antibodies,
etanercept, alefacept) --12 weeks washout period prior to randomization
d) Treatment with a non-biological investigational agent--4 weeks washout period prior to randomization
e) Treatment with a biological investigational agent--12 weeks (or 5 half-lives,
whichever is greater) washout period prior to randomization
Note: Subjects with current or history of severe psoriatic arthritis who are well-controlled on their current therapy should not be included in the study.
|E.5 End points
|E.5.1||Primary end point(s)||
|1) Primary Efficacy Endpoint for Part 1: PASI 75 response (ie, proportion of subjects with greater than or equal to 75 % improvement in PASI from Baseline) at week 16.
2) Primary Efficacy Endpoint for Part 2: PASI 75 response at week 52.
3) Primary Efficacy Endpoint for Part 3: the time at which the Week 52 improvement from baseline in PASI score is reduced by greater than 50% in subjects who attain PASI 75 at endpoint of Week 52.
Primary Safety Endpoints:
1) Percent of subjects with serious infections, defined as any infection meeting the regulatory definition of a serious adverse event, or any infection requiring IV antibiotics whether or not reported as a serious event, as per the regulatory definition.
2) Percent of subjects with malignancies
3) Percent of subjects with major cardiovascular adverse events including nonfatal stroke, non-fatal myocardial infarction or cardiovascular death
4) Percent of subjects with injection site reactions.
5) Percent of subjects with drug-related hypersensitivity reactions
-Adjudication of major cardiovascular events will be conducted by external panels. Additional CRFs will be used to record more detailed data following
occurrence of malignancies and serious infections.
|E.5.1.1||Timepoint(s) of evaluation of this end point||
|1) Baseline and Week 16
2) Week 16 and Week 52
3) Baseline and Week 52
Baseline through Week 52
|E.5.2||Secondary end point(s)||
|1) PASI 75 response at Week 12.
2) Proportion of subjects with PGA "cleared" or "minimal" at Week 16
|E.5.2.1||Timepoint(s) of evaluation of this end point||
|1) Baseline and Week 12
2) Baseline and Week 16
|E.6 and E.7 Scope of the trial
|E.6||Scope of the trial
|E.6.9||Dose response|| Yes
|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.220.127.116.11||Other trial type description||
|E.7.2||Therapeutic exploratory (Phase II)|| Yes
|E.7.3||Therapeutic confirmatory (Phase III)|| No
|E.7.4||Therapeutic use (Phase IV)|| No
|E.8 Design of the trial
|E.8.1.3||Single blind|| No
|E.8.1.4||Double blind || Yes
|E.8.1.5||Parallel group|| Yes
|E.8.1.6||Cross over || No
|E.18.104.22.168||Other trial design description||
|Third party blind - open to IMP preparer, blinded to physician, patient and sponsor
|E.8.2|| Comparator of controlled trial
|E.8.2.1||Other medicinal product(s)|| No
|E.8.2.2||Placebo || Yes
|E.8.2.4||Number of treatment arms in the trial||5
The trial involves single site in the Member State concerned
|E.8.4|| The trial involves multiple sites in the Member State concerned || No
|E.8.4.1||Number of sites anticipated in Member State concerned||10
|E.8.5||The trial involves multiple Member States|| Yes
|E.8.5.1||Number of sites anticipated in the EEA||31
|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||
|E.8.7||Trial has a data monitoring committee|| Yes
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|The overall trial ends when the last remaining subject has ended participation in the trial, by completing the trial, being discontinued from the trial, or being lost to follow-up.
|E.8.9 Initial estimate of the duration of the trial
|E.8.9.1||In the Member State concerned years||2
|E.8.9.1||In the Member State concerned months||6
|E.8.9.1||In the Member State concerned days||0
|E.8.9.2||In all countries concerned by the trial years||2
|E.8.9.2||In all countries concerned by the trial months||6
|E.8.9.2||In all countries concerned by the trial days||0