Vascular Inflammation in Psoriasis - Apremilast | NCT03082729

NCT03082729

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
97509210	Other Grant/Funding Number	Celgene

Status Module

Sponsor/Collaborators Module

Name	Class
Celgene Corporation	INDUSTRY
National Heart, Lung, and Blood Institute (NHLBI)	NIH

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
Apremilast	Other	Apremilast (Otezla), 30mg oral tablet twice per day for 52 weeks. Single arm, open label study.	Drug: Apremilast

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Apremilast	Drug	Apremilast (brand name Otezla) is a medication for the treatment of certain types of psoriasis and psoriatic arthritis.	Apremilast

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in Total Vascular Inflammation of the Aorta as Measured by FDG-PET/CT Between Baseline and Week 16.	The primary analysis will consist of comparisons of total vascular inflammation of the aorta between week 16 and baseline using [18F]-Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) / Computed Tomography (CT) (FDG-PET/CT). Tissue-to-background ratio (TBR) of the standardized uptake value (SUV) is used to assess the level of inflammation of the aorta relative to the venous blood pool (background reference).	After the completion of week 16 visit by all study participants.
Changes in Cardiometabolic Markers Between Baseline and Week 16: Ferritin	Ferritin is a marker of inflammation.	After the completion of week 16 visit by all study participants.
Changes in Cardiometabolic Markers Between Baseline and Week 16: C Reactive Protein (CRP)	CRP is a marker of inflammation.	After the completion of week 16 visit by all study participants.
Changes in Cardiometabolic Markers Between Baseline and Week 16: Intercellular Adhesion Molecule (ICAM)-1	ICAM-1 is a marker of inflammation.	After the completion of week 16 visit by all study participants.
Changes in Cardiometabolic Markers Between Baseline and Week 16: Serum Amyloid-A (SAA)	SAA is a marker of inflammation.	After the completion of week 16 visit by all study participants.
Changes in Cardiometabolic Markers Between Baseline and Week 16: Vascular Cell Adhesion Molecule (VCAM)-1

Secondary Outcomes

Measure	Description	Time Frame
Changes in Body Composition as Measured by FDG-PET/CT Between Week 52 and and Earlier Time Points (Baseline and Week 16): Visceral Adipose Tissue	Secondary analysis will consist of comparisons of change in body composition between weeks 52, 16, and baseline. Visceral adipose tissue quantification using a single CT slice at the level of the umbilicus using computer-assisted tissue segmentation (Pescatori LC et al. Quantification of visceral adipose tissue by computed tomography and magnetic resonance imaging: reproducibility and accuracy. Radiol Bras. 2019 15(1):1-6.). The values represent the cross-sectional area of the tissue segmented on the CT slice (cm^2); higher values indicate greater amount of visceral adipose tissue.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Males and females 18 years of age and older.
Clinical diagnosis of psoriasis for at least 6 months as determined by medical history interview and confirmation of diagnosis through physical examination by Investigator.
Stable plaque psoriasis for at least 2 months before screening and at baseline (Week 0) as determined by medical history interview.
Moderate to severe psoriasis defined by ≥ 10 percent Body Surface Area (BSA) involvement at the baseline (Week 0) visit.
Psoriasis Area and Severity Index (PASI) score of ≥ 12 at the Baseline (Week 0) visit.
Participant is a candidate for systemic therapy and has active psoriasis despite prior treatment with topical agents.
Women are eligible to participate in the study if they meet one of the following criteria:
Females of childbearing potential (FCBP) must have a negative pregnancy test at screening and baseline. Women of childbearing potential must undergo periodic pregnancy testing during the study and agree to use at least one of the following methods of contraception throughout the study duration and for at least 28 days after taking the last dose of investigational product:
Oral contraceptives
Transdermal contraceptives
Injectable or implantable methods
Intrauterine devices
Vaginal ring
Vasectomized partner
Barrier methods (Male or female condom (latex condom or non-latex condom NOT made out of natural [animal] membrane [for example, polyurethane]; PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.);
Women who are postmenopausal (for at least one year), sterile, or hysterectomized;
Women who have undergone tubal ligation will be required to undergo periodic pregnancy testing during the duration of the study
Sexual abstinence, defined as total abstinence from sexual intercourse, is considered an adequate form of contraception. (Agreement to comply with sexual abstinence must be recorded in the source document).
Participants using oral or parenteral forms of contraceptives must have been using these methods for at least 90 days prior to baseline visit.
Men (including those who have had a vasectomy), who engage in activity in which conception is possible, are eligible to participate if they:
Use barrier contraception (male latex condom or non-latex condom NOT made out of natural [animal] membrane [for example, polyurethane]) while on investigational product and for at least 28 days after the last dose of investigational product.
Participant is judged to be in good general health as determined by the Principal Investigator based upon the results of medical history, laboratory profile and physical examination performed at screening.

Exclusion Criteria:

Prior treatment with apremilast.
Diagnosis of erythrodermic psoriasis, generalized or localized pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis.
Diagnosis of other active skin diseases or skin infections (bacterial, fungal, or viral) that may interfere with evaluation of psoriasis.
Cannot avoid topical prescription medications for psoriasis for at least 14 days prior to the baseline visit (week 0) and during the study, with the exception of hydrocortisone 2.5% for the face and intertriginous areas.
Cannot avoid ultraviolet B (UVB) phototherapy or Excimer laser for at least 14 days prior to the Baseline (Week 0) visit and during the study.
Cannot avoid psoralen-ultraviolet A (UVA) phototherapy for at least 30 days prior to the Baseline (Week 0) visit and during the study.
Use of systemic therapies for the treatment of psoriasis, or systemic therapies known to improve psoriasis, during the study:
Systemic therapies must be discontinued at least 30 days prior to the Baseline (Week 0) visit except for biologics.
All biologics, except interleukin (IL)-12/IL-23 antagonists, must be discontinued for at least 90 days prior to Baseline (Week 0).
Any IL-12/IL-23 antagonist (e.g., ustekinumab, briakinumab) must be discontinued for at least 180 days prior to Baseline (Week 0).
Investigational agents must be discontinued at least 30 days or 5 half-lives (whichever is longer) prior to the Baseline (Week 0) visit.
Participant is ≥ 300lbs
Participant is taking or requires oral or injectable corticosteroids during the study. Inhaled corticosteroids for stable medical conditions are allowed.
Participant is taking a medication that interferes with metabolism of apremilast, including but not limited to rifampin, phenobarbital, carbamazepine, phenytoin
Poorly controlled medical condition, such as unstable ischemic heart disease, cerebrovascular accident or myocardial infarction within the prior 6 months, psychiatric disease requiring frequent hospitalization, and any other condition, which, in the opinion of the Investigator, would put the participant at risk by participation in the study.
Prior history of suicide attempt at any time in the participant's life time prior to screening or randomization, or major psychiatric illness requiring hospitalization within the last 3 years.
Uncontrolled hypertension, with measured systolic blood pressure >180 mmHg or diastolic blood pressure >95 mmHg
Participant has infection or risk factors for severe infections, for example
Positive serology or known history of HIV, hepatitis B or C, or other severe, recurrent, or persistent infections;
Excessive immunosuppression or other factors associated with it, including human immunodeficiency virus infection;
Active tuberculosis (TB) disease;
Any other significant infection requiring hospitalization or intravenous (IV) antibiotics in the 30 days prior to baseline;
Infection requiring treatment with oral or parenteral (other than IV) antibiotics within 14 days prior to baseline;
Participant has received vaccination with a live viral agent within 30 days prior to screening or will require a live vaccination during study participation including up to 30 days after the last dose of study drug.
Participant has history of hematological or solid malignancy other than successfully treated basal cell carcinoma, non-metastatic cutaneous squamous cell carcinoma or cervical intraepithelial neoplasia or carcinoma in situ of cervix with no evidence of recurrence within the previous 5 years.
Female participant who is pregnant or breast-feeding or considering becoming pregnant during the study.
Screening clinical laboratory analyses showing any of the following abnormal results:
White blood cell (WBC) count <3.0 x 109/L. (Subject can be included if WBC count is <3.0 x 109/L and absolute neutrophil count (ANC) is >1000 cells / mm3.)
WBC count > 15 x 109/L;
Hemoglobin (Hgb) < 9.0 x 109/L;
Platelet count < 100 x 109/L;
Serum creatinine >1.5 mg/dL ;
Serum aspartate transaminase or alanine transaminase >2.0 upper limits of normal
Recent history of substance abuse or psychiatric illness that could preclude compliance with the protocol.
History of substance abuse within 365 days of screening visit.
Alcohol use of more than 14 drinks per week within 14 days of the baseline visit
If subject is on cholesterol-lowering medication (e.g. statin), dose and form of medication must be stable for 90 days prior to week 0 and remain stable throughout the duration of the study.

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
University of Southern California		Los Angeles	California	90033	United States
Derm Associates, P.C.

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
36129688	Derived	Gelfand JM, Shin DB, Armstrong AW, Tyring SK, Blauvelt A, Gottlieb S, Lockshin BN, Kalb RE, Fitzsimmons R, Rodante J, Parel P, Manyak GA, Mendelsohn L, Noe MH, Papadopoulos M, Syed MN, Werner TJ, Wan J, Playford MP, Alavi A, Mehta NN. Association of Apremilast With Vascular Inflammation and Cardiometabolic Function in Patients With Psoriasis: The VIP-A Phase 4, Open-label, Nonrandomized Clinical Trial. JAMA Dermatol. 2022 Dec 1;158(12):1394-1403. doi: 10.1001/jamadermatol.2022.3862.

IPD Sharing Statement Module

Arm/Group Information

ID	Title	Description
FG000	Apremilast	Apremilast (Otezla), 30mg oral tablet twice per day for 52 weeks. Single arm, open label study. Apremilast: Apremilast (brand name Otezla) is a medication for the treatment of certain types of psoriasis and psoriatic arthritis.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG00070 subjects
Per Protocol Population Week 16		FG00060 subjects
COMPLETED		FG00039 subjects
NOT COMPLETED		FG00031 subjects

Type	Comment	Reasons
Lost to Follow-up		FG0007 subjects
Physician Decision		FG0002 subjects
Withdrawal by Subject		FG0001 subjects

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Apremilast	Apremilast (Otezla), 30mg oral tablet twice per day for 52 weeks. Single arm, open label study. Apremilast: Apremilast (brand name Otezla) is a medication for the treatment of certain types of psoriasis and psoriatic arthritis.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change in Total Vascular Inflammation of the Aorta as Measured by FDG-PET/CT Between Baseline and Week 16.

The primary analysis will consist of comparisons of total vascular inflammation of the aorta between week 16 and baseline using [18F]-Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) / Computed Tomography (CT) (FDG-PET/CT). Tissue-to-background ratio (TBR) of the standardized uptake value (SUV) is used to assess the level of inflammation of the aorta relative to the venous blood pool (background reference).

The number of subjects analyzed reflect availability of analyzable samples.

Posted

Mean

Standard Error

ratio

After the completion of week 16 visit by all study participants.

ID	Title	Description
OG000	Apremilast	Apremilast (Otezla), 30mg oral tablet twice per day for 52 weeks. Single arm, open label study. Apremilast: Apremilast (brand name Otezla) is a medication for the treatment of certain types of psoriasis and psoriatic arthritis.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Apremilast	Apremilast (Otezla), 30mg oral tablet twice per day for 52 weeks. Single arm, open label study. Apremilast: Apremilast (brand name Otezla) is a medication for the treatment of certain types of psoriasis and psoriatic arthritis.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Stroke	Vascular disorders		Non-systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Nausea	Gastrointestinal disorders		Non-systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Joel Gelfand, MD, MSCE	University of Pennsylvania	215-662-2737		joel.gelfand@pennmedicine.upenn.edu

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Dec 13, 2021	Aug 15, 2022	Prot_SAP_000.pdf

Submission Tracking

Condition Browse Module

ID	Term
D011565	Psoriasis
D002318	Cardiovascular Diseases

ID	Term
D017444	Skin Diseases, Papulosquamous
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

Intervention Browse Module

ID	Term
C505730	apremilast

Masking Info

VCAM-1 is a marker of inflammation.

EG0001 events1 affected70 at risk

EG00014 affected70 at risk