Vascular Inflammation in Psoriasis - Apremilast

NCT03082729 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: 82665297509210
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 7

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.

Conditions

Psoriasis; Cardiovascular Diseases

Outcome Measures

Primary Outcomes (69)

• 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

  VCAM-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: Interferon (IFN)-Gamma

  IFN-gamma 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: Interleukin (IL)-1b

  IL-1b 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: IL-10

  IL-10 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: IL-17A

  IL-17A 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: IL-6

  IL-6 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: IL-8

  IL-8 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: IL-9

  IL-9 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: Monocyte Chemoattractant Protein (MCP)-1

  MCP-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: Tumor Necrosis Factor (TNF)-Alpha

  TNF-alpha 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: IL2RA

  IL2RA 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: GlycA

  GlycA 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: Cholesterol Efflux Capacity

  Cholesterol Efflux Capacity is a marker of lipid function and metabolism. The ability to promote cholesterol efflux from macrophages is a classic function of HDL that is thought to be an important mechanism by which HDL protects against atherosclerosis. HDL cholesterol efflux capacity assays are performed based on published methods using J774 cells derived from a murine macrophage cell line (Mehta NN Atherosclerosis 2012). Efflux is calculated as a unitless measure by using the following formula: \[(µCi of 3H-cholesterol in media containing apoB-depleted subject plasma - µCi of 3H-cholesterol in plasma-free media) / (µCi of 3H-cholesterol in media containing apoB-depleted pooled control plasma-µCi of 3H-cholesterol in pooled control plasma-free media)\]. Cholesterol efflux capacity is inversely correlated with incidence of cardiovascular events (i.e. higher cholesterol efflux capacity is better for patients).

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Triglyceride

  Triglyceride is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Total Cholesterol

  Total Cholesterol is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: High-density Lipoprotein (HDL) - Cholesterol (C)

  HDL-C is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: HDL-Particle Number (P)

  HDL-P is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: HDL-Particle Size (Z)

  HDL-Z is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Small (S)-HDL-P

  S-HDL-P is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Medium (M)-HDL-P

  M-HDL-P is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Large and Medium (LM)-HDL-P

  LM-HDL-P is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Large (L)-HDL-P

  L-HDL-P is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Low-density Lipoprotein (LDL)-C

  LDL-C is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: LDL-P

  LDL-P is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: LDL-Z

  LDL-Z is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: S-LDL-P

  S-LDL-P is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: L-LDL-P

  L-LDL-P is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Very Large (VL)-LDL-P

  VL-LDL-P is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Very Low-density Lipoprotein (VLDL)-P

  VLDL-P is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: VLDL-Z

  VLDL-Z is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: VLDL-Triglycerides (TG)

  VLDL-TG is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: S-VLDL-P

  S-VLDL-P is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: M-VLDL-P

  M-VLDL-P is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: LM-VLDL-P

  LM-VLDL-P is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: L-VLDL-P

  L-VLDL-P is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Intermediate-density Lipoprotein (IDL)-P

  IDL-P is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Apolipoprotein A1 (ApoA1)

  ApoA1 is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Apolipoprotein B (ApoB)

  ApoB is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: TRLTG

  TRLTG is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: (Triglyceride-Rich Lipoprotein Cholesterol) TRLC

  TRLC is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: (Triglyceride-Rich Lipoprotein) TRLP

  TRLP is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: VS-TRLP

  VS-TRLP is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: S-TRLP

  S-TRLP is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: M-TRLP

  M-TRLP is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: L-TRLP

  L-TRLP is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: VL-TRLP

  VL-TRLP is a marker of lipid function and metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Insulin

  Insulin is a marker of glucose metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)

  HOMA-IR is a marker of glucose metabolism. HOMA-IR, a method used to quantify insulin resistance and beta-cell function, is expressed using fasting blood glucose and insulin levels. It is calculated using the formula (HOMA-IR = fasting glucose \[mg/dl\] \* fasting insulin \[mU/ml\]/405).

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Glucose

  Glucose is a marker of metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Diabetes Risk Index (DRI)

  DRI is a marker of glucose metabolism. DRI is a nuclear magnetic resonance spectroscopy (NMR)-derived multimarker score (values 1-100) that predicts a patient's risk of developing type 2 diabetes mellitus (T2D) independent of glycemic status. DRI derives its performance from the weighted addition of the Lipoprotein Insulin Resistance Index (LP-IR) scores with simultaneously-measured levels of branched-chain amino acids (BCAA). Higher scores indicate greater risk.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Lipoprotein Insulin Resistance Index (LP-IR)

  LP-IR is a marker of glucose metabolism. LP-IR is a marker of insulin resistance, and as such the LP-IR score predicts a patient's likelihood of future development of type 2 diabetes. LP-IR is a multimarker index (values 0-100) based on the concentrations of particular lipoprotein subclasses. Greater score indicates higher likelihood of developing diabetes.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Leptin

  Leptin is a marker of adipose dysfunction and general metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Adiponectin

  Adiponectin is a marker of adipose dysfunction and general metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Fetuin A

  Fetuin A is a marker of adipose dysfunction and general metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Citrate

  Citrate is a marker of adipose dysfunction and general metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Valine

  Valine is a marker of adipose dysfunction and general metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Leucine

  Leucine is a marker of adipose dysfunction and general metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Isoleucine

  Isoleucine is a marker of adipose dysfunction and general metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Alanine

  Alanine is a marker of adipose dysfunction and general metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: BCAA

  Branched-chain amino acids (BCAA) is a marker of adipose dysfunction and general metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Ketone Bodies

  Ketone Bodies are markers of adipose dysfunction and general metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Beta Hydroxybutyrate

  Beta Hydroxybutyrate is a marker of adipose dysfunction and general metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Acetoacetic Acid

  Acetoacetic Acid is a marker of adipose dysfunction and general metabolism.

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

• Changes in Cardiometabolic Markers Between Baseline and Week 16: Acetone

  Acetone is a marker of adipose dysfunction and general metabolism.

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

Secondary Outcomes (76)

• 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

  After the completion of week 52 visit by all study participants.

• Changes in Body Composition as Measured by FDG-PET/CT Between Week 52 and and Earlier Time Points (Baseline and Week 16): Subcutaneous Adipose Tissue

  After the completion of week 52 visit by all study participants.

• Changes in Physician Reported Outcomes: Psoriasis Area and Severity Index (PASI)

  Baseline, week 16, and week 52.

• Changes in Physician Reported Outcomes: Physician Global Assessment (PGA)

  Baseline, week 16, and week 52.

• Changes in Patient Reported Outcomes: Dermatology Life Quality Index (DLQI)

  Baseline, week 16, and week 52.

Study Arms (1)

Apremilast

OTHER

Apremilast (Otezla), 30mg oral tablet twice per day for 52 weeks. Single arm, open label study.

Drug: Apremilast

Interventions

Apremilast DRUG

Apremilast (brand name Otezla) is a medication for the treatment of certain types of psoriasis and psoriatic arthritis.

Also known as: Otezla

Apremilast

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Males and females 18 years of age and older.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.);

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead
• Celgene Corporation: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (7)

University of Southern California

Los Angeles, California, 90033, United States

Location

Derm Associates, P.C.

Rockville, Maryland, 20850, United States

Location

Buffalo Medical Group, P.C.

Buffalo, New York, 14221, United States

Location

Oregon Medical Research Center

Portland, Oregon, 97223, United States

Location

Dermatology and Skin Surgery Center

Exton, Pennsylvania, 19341, United States

Location

The University of Pennsylvania

Philadelphia, Pennsylvania, 19140, United States

Location

Center for Clinical Studies

Houston, Texas, 77004, United States

Location

Related Publications (1)

• 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.

  PMID: 36129688 DERIVED

MeSH Terms

Conditions

Psoriasis; Cardiovascular Diseases

Interventions

apremilast

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

The lack of placebo control; The number of biomarkers assessed may result in alpha error given the large number of pathways interrogated and thus the cardiometabolic biomarkers may be considered exploratory; Only surrogate markers evaluated and not actual clinical events.

Results Point of Contact

• Title: Joel Gelfand, MD, MSCE
• Organization: University of Pennsylvania

joel.gelfand@pennmedicine.upenn.edu

215-662-2737

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2017
• First Posted: March 17, 2017
• Study Start: April 24, 2017
• Primary Completion: August 17, 2021
• Study Completion: August 17, 2021
• Last Updated: November 10, 2022
• Results First Posted: November 10, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)