Vascular Inflammation in Psoriasis - Apremilast (VIP-A)

• ClinicalTrials.gov Identifier: NCT03082729
• Recruitment Status: Completed
• First Posted: March 17, 2017
• Last Update Posted: January 14, 2022
• Sponsor: University of Pennsylvania
• Collaborators: Celgene Corporation; National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): University of Pennsylvania

Study Description

Brief Summary:

The purpose of the VIP-A study is to determine the effect of apremilast on aortic vascular inflammation, cardiometabolic biomarkers and body composition in patients with moderate-severe psoriasis.

Condition or disease	Intervention/treatment	Phase
Psoriasis; Cardiovascular Diseases	Drug: Apremilast	Phase 4

Detailed Description:

The primary objectives of this study are to determine the effect of apremilast on aortic vascular inflammation, cardiometabolic biomarkers and body composition in patients with moderate-severe psoriasis. FDG-PET/CT will be used to assess vascular inflammation, with multi-volumetric product, tissue-to-background ratio and total atherosclerotic burden, and body composition via volumetric quantification. This is a year-long, single arm, open label study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 70 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: Imaging data files will be sent to the central core of the National Institutes of Health (NIH) Imaging Lab for measuring the standardized uptake values (SUVs). The NIH central PET/CT readers will be blinded to time point of scan via Digital Imaging and Communication in Medicine (DICOM) file editing applied by the University of Pennsylvania.
• Primary Purpose: Treatment
• Official Title: A Phase IV, Open Label Study of the Effects of Apremilast on Vascular Inflammation and Cardiometabolic Function in Psoriasis
• Actual Study Start Date: April 24, 2017
• Actual Primary Completion Date: August 17, 2021
• Actual Study Completion Date: August 17, 2021

Arms and Interventions

Arm	Intervention/treatment
Apremilast; Apremilast (Otezla), 30mg oral tablet twice per day for 52 weeks. Single arm, open label study.	Drug: Apremilast; Apremilast (brand name Otezla) is a medication for the treatment of certain types of psoriasis and psoriatic arthritis.; Other Name: Otezla

Outcome Measures

Primary Outcome Measures :

1. Change in total vascular inflammation of the aorta as measured by [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) / computed tomography (CT) (FDG-PET/CT) between baseline and week 16. [ Time Frame: After the completion of week 16 visit by all study participants. ]
   The primary analysis will consist of comparisons of total vascular inflammation of the aorta between week 16 and baseline using.
2. Changes in cardiometabolic markers between baseline and week 16. [ Time Frame: After the completion of week 16 visit by all study participants. ]
   Carbiometabolic markers will include: lipid particle size, HDL function (cholesterol efflux), TNF-Alpha, IL-6, high sensitivity C reactive protein, leptin, adiponectin, insulin levels and glucose to yield HOMA-IR, apolipoprotein B, ferritin, interleukin-2 receptor A, interleukin-18, and fetuin-A.

Secondary Outcome Measures :

1. Changes in body composition as measured by FDG-PET/CT between week 52 and and earlier time points (baseline and week 16). [ Time Frame: After the completion of week 52 visit by all study participants. ]
   Secondary analysis will consist of comparisons of change in body composition between weeks 52, 16, and baseline.
2. Changes in physician reported outcomes (Psoriasis Area and Severity Index (PASI), Physician Global Assessment (PGA)) between week 52 and and earlier time points (baseline and week 16). [ Time Frame: After the completion of week 52 visit by all study participants. ]
   Secondary analysis will consist of comparisons of change in PASI and PGA scores between weeks 52, 16, and baseline.
3. Changes in patient reported outcomes (DLQI, pruritis by Visual Analog Scales (VAS)) between week 52 and and earlier time points (baseline and week 16). [ Time Frame: After the completion of week 52 visit by all study participants. ]
   Secondary analysis will consist of comparisons of change in DLQI and VAS scores between weeks 52, 16, and baseline.
4. Change in total vascular inflammation of the aorta as measured by [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) / computed tomography (CT) (FDG-PET/CT) between week 52 and earlier time points (baseline and week 16). [ Time Frame: After the completion of week 52 visit by all study participants. ]
   Secondary analysis will consist of comparisons of total vascular inflammation of the aorta between week 52, 16, and baseline.
5. Change in cardiometabolic markers between week 52 and earlier time points (baseline and week 16). [ Time Frame: After the completion of week 52 visit by all study participants. ]
   Cardiometabolic markers will include: : lipid particle size, HDL function (cholesterol efflux), TNF-Alpha, IL-6, high sensitivity C reactive protein, leptin, adiponectin, insulin levels and glucose to yield HOMA-IR, apolipoprotein B, ferritin, interleukin-2 receptor A, interleukin-18, and fetuin-A.
6. Adverse events AE) and serious AEs reported by study participants will be monitored and a complete review of systems and blood laboratory evaluation will be conducted during screening, week 16, and week 52 for safety endpoints. [ Time Frame: At all study visits throughout one-year study. ]
   Safety endpoints will be assessed by participant interview and physical exam and blood laboratory examination, if indicated.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Males and females 18 years of age and older.
• Accepts Healthy Volunteers: No

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.
• 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 UVB phototherapy or Excimer laser for at least 14 days prior to the Baseline (Week 0) visit and during the study.
• Cannot avoid psoralen-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 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 and Locations

Locations

United States, California

University of Southern California

Los Angeles, California, United States, 90033

United States, Maryland

Derm Associates, P.C.

Rockville, Maryland, United States, 20850

United States, New York

Buffalo Medical Group, P.C.

Buffalo, New York, United States, 14221

United States, Oregon

Oregon Medical Research Center

Portland, Oregon, United States, 97223

United States, Pennsylvania

Dermatology and Skin Surgery Center

Exton, Pennsylvania, United States, 19341

The University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19140

United States, Texas

Center for Clinical Studies

Houston, Texas, United States, 77004

Sponsors and Collaborators

University of Pennsylvania

Celgene Corporation

National Heart, Lung, and Blood Institute (NHLBI)

More Information

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT03082729
• Other Study ID Numbers: 826652; 97509210 ( Other Grant/Funding Number: Celgene )
• First Posted: March 17, 2017
• Last Update Posted: January 14, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Cardiovascular Diseases; Psoriasis; Inflammation; Pathologic Processes; Skin Diseases, Papulosquamous; Skin Diseases; Apremilast; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Phosphodiesterase 4 Inhibitors; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action