A Study to Evaluate Safety and Efficacy of Toreforant (JNJ-38518168) in Participants With Moderate to Severe Plaque-type Psoriasis

• Register: EUCTR
• Last refreshed on: 22 August 2016
• Main ID: EUCTR2015-000277-12-PL
• Date of registration: 05/03/2015
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V.
• Public title: A Study to Evaluate Safety and Efficacy of Toreforant (JNJ-38518168) in Participants With Moderate to Severe Plaque-type Psoriasis
• Scientific title: A Phase 2 Multicenter, Randomized, Double-blind, Placebo-Controlled Trial to Evaluate Toreforant (JNJ-38518168) for the Treatment of Subjects with Moderate to Severe Plaquetype Psoriasis
• Date of first enrolment: 28/04/2015
• Target sample size: 66
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000277-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Poland, United States

Contacts

• Name: Clinical Registry group
• Affiliation: Janssen-Cilag International N.V.

• Name: Clinical Registry group
• Affiliation: Janssen-Cilag International N.V.

Key inclusion & exclusion criteria

Inclusion criteria:
- Subject must be a man or woman =18 years of age.
- Subject must have a diagnosis of plaque-type psoriasis (with or without PsA) for at least 6 months before the first administration of study drug.
- Subject must have a PASI =12 at screening and at baseline.
- Subject must have an IGA =3 at screening and at baseline.
- Subject must have a BSA =10% at screening and at baseline.
At screening, the results of the following laboratory tests performed at the central laboratory must be within the limits specified below. Note: except for ferritin, the investigator may consider the subject eligible if the previously abnormal laboratory test result is within normal range on a repeat testing in the central laboratory. Only 1 repeat testing is allowed. No repeat testing for ferritin is allowed.
a. Serum alanine aminotransferase levels (ALT): =1.5 x upper limit of normal (ULN)
b. Total bilirubin level: =1.5 x ULN
c. Hemoglobin: =10 g/dL (International System of Units [SI]: =100 g/L)
d. WBC: =3.0 x 103 cells/mm3 (SI: =3.0 x109 cells/L)
e. Platelets: =100 x 103 cells/mm3 (SI: =100 x 109 cells/L)
f. Neutrophils: =1.5 x 103 cells/mm3 (SI: =1.5 x 109 cells/L)
g. Ferritin: =500 ng/mL (SI: =500 µg/L)
If the results of clinical laboratory tests (including serum chemistry, hematology, and urinalysis) other than those specified above are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the subject's source documents and initialed by the investigator.
Subject must be otherwise healthy and medically stable on the basis of physical examination, medical history, vital signs, and 12-lead ECG performed at screening. If there are abnormalities, they must be consistent with the underlying illness in the study population. This determination must be recorded in the subject's source documents and initialed by the investigator.
- Subject must agree to avoid prolonged sun exposure and avoid use of tanning booths or other ultraviolet light sources during study.
- Before randomization, a woman must be either: Not of childbearing potential: premenarchal; postmenopausal (>45 years of age with amenorrhea for at least 12 months or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone (FSH) level >40 IU/L); permanently sterilized (eg, tubal occlusion, hysterectomy, bilateral salpingectomy); or otherwise be incapable of pregnancy, Of childbearing potential and practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: eg, established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods: condom with spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner sterilization (the vasectomized partner should be the sole partner for that subject); true abstinence. Note: If the childbearing potential changes after start of the study (eg, woman who is not heterosexually active becomes active, premenarchal woman experiences menarche) a woman must begin a highly effective method of birth contro
Exclusion criteria:
Any potential subject who meets any of the following criteria:
- Subject has a history or current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease.
- Subject has a current malignancy or history of malignancy within 5 years before screening.
- Subject has a history of lymphoproliferative disease, including lymphoma; a history of monoclonal gammopathy of undetermined significance (MGUS); or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy or splenomegaly.
- Subject has 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), fungal infection (mucocutaneous candidiasis), or open, draining, or infected skin wounds or ulcers.
- Subject has a history of an infected joint prosthesis, or has received antibiotics for a suspected infection of a joint prosthesis, if that prosthesis has not been removed or replaced.
- Subject has a transplanted organ
- Subject is infected with human immunodeficiency virus (HIV); positive serology for HIV antibody as confirmed by Western blot.
- Subject tests positive for acute or chronic hepatitis B virus (HBV) infection at the screening visit or has screening serology consistent with hepatitis C infection (seropositive for antibodies to hepatitis C virus (HCV), unless they have a negative HCV RNA test result within 6 months prior to the screening visit and have a second negative HCV RNA test result at the screening visit.
- Subject has a personal or familial history or risk of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS), including but not limited to, RA, systemic idiopathic juvenile arthritis (SiJA), or adult onset Still's disease (AOSD).
- Subject has moderate or severe renal insufficiency as measured by creatinine clearance (CrCL) less than 50 mL/min as calculated by Cockcroft-Gault formula: CrCL = (140 minus age) x ideal body weight (in kg) x 0.85 (if, female)/72 x serum creatinine (in mg/dL).
- Subject has a QTcF interval >450 msec at either the screening visit or Day 1/Week 0, has a complete left or right bundle branch block, or has a history or current evidence of additional risk factors for torsades de pointes.
- Subject has received drugs with a risk of torsades de pointes within 2 weeks or within 5 half-lives of the drug, whichever is longer, prior to the first administration of study drug.
- Subject has received drugs that are moderate/strong inducers or inhibitors of CYP3A4 or drugs that are inducers or inhibitors of Pgp within 2 weeks or within 5 half-lives of the drug, whichever is longer, prior to the first dose of study medication.
- Subject has received drugs that are substrates of CYP2C8 , any drugsthat are substrates of hOCT2 (except cimetidine, famotidine, and ranitidine), or any drugs that are substrates of CYP3A with narrow therapeutic range within 2 weeks or within 5 half-lives of the drug, whichever is longer, prior to the first dose of study medication.
- Subject has a nonplaque form of psoriasis.
- Subject has current drug-induced psoriasis
- Subject has ever received any previous biologic therapy for psoriasis or psoriatic arthritis.
- Subject has received any biolo

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderate to severe plaque-type psoriasis.
MedDRA version: 17.1 Level: LLT Classification code 10071117 Term: Plaque psoriasis System Organ Class: 100000004858

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Intervention(s)

Product Name: Toreforant (JNJ-38518168)
Product Code: Toreforant (JNJ-38518168)
Pharmaceutical Form: Tablet
INN or Proposed INN: toreforant
CAS Number: 1203558-77-3
Current Sponsor code: JNJ-38518168
Other descriptive name: JNJ-38518168-ZBQ
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Toreforant (JNJ-38518168)
Product Code: Toreforant (JNJ-38518168)
Pharmaceutical Form: Tablet
INN or Proposed INN: toreforant
CAS Number: 1203558-77-3
Current Sponsor code: JNJ-38518168
Other descriptive name: JNJ-38518168-ZBQ
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To assess the impact of treatment with JNJ-38518168 on selected biomarkers.
To characterize the population pharmacokinetics of JNJ-38518168 in subjects with psoriasis.
To evaluate the relationship between exposure to JNJ-38518168 and appropriate efficacy/safety outcomes (eg, Psoriasis Activity Severity Index [PASI] 75).

Timepoint(s) of evaluation of this end point: The primary endpoint is the proportion of subjects who achieve a PASI 75 response at Week 12.

Main Objective: To evaluate the efficacy of JNJ-38518168 in subjects with moderate to severe plaque-type psoriasis.
To assess the safety and tolerability of JNJ-38518168 in subjects with moderate to severe plaque-type psoriasis.

Primary end point(s): The primary endpoint is the proportion of subjects who achieve a PASI 75 response at Week 12.

Secondary Outcome(s)

Secondary end point(s): The major secondary endpoint is the proportion of subjects who achieve a score of 0 or 1 on the
IGA at Week 12.
Other secondary endpoints include:
- The proportion of subjects who achieve PASI 50, PASI 75, PASI 90 and PASI 100 responses over time.
- The percent improvement from baseline in PASI over time.
- The proportion of subjects who achieve the following IGA responses over time: IGA of 0, 1 or 2; IGA of 0 or 1; and IGA of 0.
- The change from baseline in PSSD symptom and sign score at Week 12.
- The proportion of subjects who achieve a PSSD symptom score of 0 or a PSSD sign score of 0 at Week 12 for subjects with baseline scores = 1.
- The proportion of subjects with each PSSD individual scale score of 0 at Week 12 among subjects with scale score =1 at baseline.

Timepoint(s) of evaluation of this end point: The major secondary endpoint is the proportion of subjects who achieve a score of 0 or 1 on the IGA at Week 12.

The study will employ an adaptive design in which dose assignments will depend on the results of up to 2 interim analyses. Approximately 66 subjects will be randomized to JNJ 38518168 or placebo in an approximately 10:1 ratio. The possible JNJ 38518168 dose groups will be 3 mg once daily, 30 mg once daily, or 60 mg once daily. The first group of subjects will be randomized to either JNJ 38518168 30 mg or placebo. The 2 interim analyses will take place at 2 times during the study, and the results will be used to determine the dose of JNJ 38518168 (60 mg or 3 mg) used for the next group of enrolled subjects.

Secondary ID(s)

38518168PSO2001

Source(s) of Monetary Support

Janssen Research & Development, LLC