| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate-to-Severe Plaque Psoriasis |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10071117 |
| E.1.2 | Term | Plaque psoriasis |
| E.1.2 | System Organ Class | 100000004858 |
|
| 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 |
| 1. Assess whether BMS-986165 is superior to placebo at Week 16 in the treatment of subjects with moderate-to-severe plaque psoriasis |
|
| E.2.2 | Secondary objectives of the trial |
2. Assess whether BMS-986165 is superior to apremilast at Week 16
3. Assess whether BMS-986165 is superior to apremilast at Week 52
4. Assess whether BMS-986165 is superior to placebo over the first 16 weeks of treatment
5. Assess whether BMS-986165 is superior to apremilast over 52 weeks of treatment
6. Evaluate improvement in patient-reported outcomes for BMS-986165 compared with placebo through Week 16
7. Evaluate improvement in patient-reported outcomes for BMS-986165 compared with apremilast through Week 24
8. Evaluate maintenance of efficacy of BMS-986165 through Week 52 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
1) Signed Written Informed Consent
a) Subjects must be willing to participate in the study and sign the informed consent form (ICF)
2) Type of Subject and Target Disease Characteristics
a) Men and women diagnosed with stable plaque psoriasis for 6 months or more. Stable psoriasis is defined as no morphology changes or significant flares of disease activity in the opinion of the investigator
b) Deemed by the investigator to be a candidate for phototherapy or systemic therapy
c) ≥10% of BSA involvement at Screening Visit and Day 1
d) Psoriasis Area and Severity Index (PASI) score ≥12 and static Physician’s Global Assessment (sPGA) ≥3 at Screening Visit and Day 1
3) Age and Reproductive Status
a) Men and women aged ≥18 years at the time of Screening Visit
b) Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at Screening Visit, and a negative urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [hCG]) within 24 hours prior to the start of study drug
c) Women must not be pregnant, lactating, breastfeeding, or planning pregnancy during the study period
d) Women of childbearing potential must agree to use correctly a highly effective method(s) of contraception for the duration of treatment (52 weeks) with study drug(s) BMS-986165
plus 5 half-lives of study drug (3 days) plus 30 days (duration of ovulatory cycle) for a total of 33 days post-treatment completion (total of 33 days after last dose of study drug).
WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements, but must still undergo pregnancy testing as described in this protocol
e) Male subjects who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception (APPENDIX 4) for the duration of treatment with study treatment(s) plus 5 half-lives of the study treatment (3 days) for a total of 3 days post-treatment completion. In addition, male subjects must be willing to refrain from sperm donation during this time |
|
| E.4 | Principal exclusion criteria |
1)Target Disease Exceptions
a)Has nonplaque psoriasis at Screening or Day1(D1)
2)Infectious/Immune-related Exclusions
a)History or evidence of outpatient active infection and/or febrile illness
within 7 days prior to D1
b)History of serious bacterial, fungal, or viral infection requiring hospitalization and IV antimicrobial treatment within 60 days prior to
D1
c)Untreated bacterial infection within 60 days prior to D1
d)Ongoing evidence of chronic, bacterial infection
e)History of proven infection of a joint prosthesis
f)Received live vaccines within 60 days prior to D1, or plans to receive a live vaccine during the study, or within 60 days after completing study treatment
g)Presence of herpes zoster lesions at Screening or D1
h)History of serious herpes zoster or serious herpes simplex infection
i+j)Evidence of, or test positive for HBV and HCV at Screening
k)Positive for HIV-1 and -2 Ab at Screening
l)History of known or suspected congenital or acquired immunodeficiency state or condition that would compromise the subject's immune status
3)Any of the following TB criteria
a)History of active TB prior to Screening
b)Signs or symptoms of active TB during screening
c)Any imaging of the chest showing evidence of current active or history
of active pulmonary TB
d)Latent TB infection defined as positive IFN gamma release assay at Screening, in the absence of clinical manifestations
4)Medical History and Concurrent Diseases
a)Any major surgery within 8 weeks prior to D1, or any planned surgery for the first 52 weeks of the study
b)Donated blood >500mL within 4 weeks prior to D1, or plans to donate blood during the course of the study
c)Drug or alcohol abuse, as determined by the investigator, within 6 months prior to D1
d)Medical marijuana
e)Major illness/condition or evidence of an unstable clinical condition that will substantially increase the risk of participation
f)Unstable cardiovascular disease
g)Uncontrolled arterial hypertension characterized by a systolic blood
pressure (BP) >160mmHg or diastolic BP >100mmHg
h)Class III or IV congestive heart failure
i)Has cancer or history of cancer or lymphoproliferative disease within
the previous 5 years
j)Significant/uncontrolled neuropsychiatric illness judged as clinically
significant by the investigator during Screening or at D1
OR Any lifetime history of suicidal ideation, suicidal behavior, or suicidal
attempts at Screening or at D1, or is clinically deemed to have suicide risk
k)Prior exposure to investigational product (ie, BMS-986165 or apremilast)
l)If the subject has received biologics previously, exclusion criteria for
washout will apply
m)Received systemic nonbiologic psoriasis medications and/or any systemic immunosuppressants within 4 weeks prior to D1
n)Used leflunomide within 6 months prior to D1
o)Used opioid analgesics within 4 weeks prior to D1
p)Received lithium, antimalarials, or intramuscular gold within 4 weeks
of the first administration of any study medication
q)Used any strong CYP450 inducers within 4 weeks prior to D1
r)Received phototherapy within 4 weeks prior to D1
s)Used topical medications/treatments that could affect psoriasis
evaluation within 2 weeks prior to D1
t)Use of shampoos that contain corticosteroids, coal tar, >3% salicylic
acid, or vitamin D3 analogues within 2 weeks prior to D1
u)Received an experimental antibody or experimental biologic therapy
within the previous 6 months, OR received any other experimental
therapy or new investigational agent within 30 days or 5 half-lives
(whichever is longer) prior to D1 OR is currently enrolled in an
investigational study
v)any other reason as determined by investigator
5)Physical and Lab Evaluations
a)At Screening
i)Absolute WBC<3000/mm3
ii)Absolute lymphocyte<500/mm3
iii)Absolute neutrophil<1000/mm3
iv)Platelet <100,000/mm3
v)Hemoglobin <9g/dL
vi)ALT and/or AST >3× upper limit of normal (ULN)
vii)Total unconjugated and/or conjugated bilirubin >2× ULN
viii)TSH outside the normal reference range and free T4 or T3 outside
normal range
b)ECG abnormalities that are considered clinically significant and pose
an unacceptable risk to the subject if participating in the study
c)Renal impairment based on an estimated glomerular filtration rate
(eGFR) <45mL/min
d)Inability to be venipunctured and/or tolerate venous access
e)Other significant laboratory abnormalities that might place the subject at unacceptable risk for participation
6)Allergies and Adverse Drug Reactions
a)History of any significant drug allergy
7)Other Exclusion Criteria
a)Prisoners or subjects who are involuntarily incarcerated
b)Subjects who are compulsorily detained for treatment of either a
psychiatric or physical illness
c)Inability to comply with restrictions and prohibited activities/treatments as listed in the study protocol
d)Site personnel or their immediate family
e)Contraindications on the label for apremilast |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
2. - 5. sPGA 0/1, PASI 75, PASI 90, sPGA 0, PASI 100
6. - 7.
• Change from baseline in Psoriasis Symptoms and Signs Diary (PSSD)
symptom score and total score
8.
• Time to first loss of PASI 75 among subjects that are PASI 75
responders at Week 24
• PASI 75 responders at Week 52 and Week 24
• sPGA 0/1 responders at Week 52 and Week 24
• PASI 90 responders at Week 52 and Week 24 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
sPGA 0/1 and PASI 75 at Week 16
sPGA 0 at Week 16
PASI 90 at Week 16 and Week 52
PASI 100 at Week 16 |
|
| 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 | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| 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) | 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 | Yes |
| E.8.1.5 | Parallel group | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| 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 | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 51 |
| 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 |
| Canada |
| France |
| Germany |
| Japan |
| Korea, Republic of |
| Netherlands |
| Norway |
| Poland |
| Russian Federation |
| Spain |
| Taiwan |
| United Kingdom |
| United States |
|
| 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 | 1 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 24 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 27 |
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