Vascular Inflammation in Psoriasis - Extension Study | NCT01866592

NCT01866592

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Sponsor/Collaborators Module

Name	Class
AbbVie	INDUSTRY

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

Arm Groups

Label	Type	Description	Intervention Names
Single-Arm, open-label extension trial	Other	Single-arm, open label extension trial to continue treatment with Humira (Adalimumab) subcutaneous injection 80mg initial dose followed by 40mg maintenance dose every other week for up to 52 weeks.	Drug: Adalimumab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Adalimumab	Drug	Study participants will receive the FDA-approved dosing schedule for Adalimumab (Humira): an initial dose of 80mg followed by a 40mg maintenance dose every other week up to 52 weeks.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in Vascular Inflammation	Change in total vascular inflammation of five aortic segments as assessed on FDG-PET/CT between week 52 of the adalimumab treatment period and baseline scans (prior to randomization in the VIP Trial). The arterial uptake of FDG is measured by the standardized uptake value (SUV) max divided by the venous SUIV mean yielding a target to background ration (TBR). If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).	52 weeks (continuation group) or 64 weeks (crossover group)
Change in Vascular Inflammation	Change in total vascular inflammation of five aortic segments as assessed on FDG-PET/CT between week 52 of the adalimumab treatment period and start of adalimumab.The arterial uptake of FDG is measured by the standardized uptake value (SUV) max divided by the venous SUIV mean yielding a target to background ration (TBR).	52 weeks of adalimumab treatment
Change in Cardiometabolic Biomarker - Total Cholesterol	Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Total Cholesterol. If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).	52 weeks (continuation group) or 64 weeks (crossover group)
Change in Cardiometabolic Biomarker - Cholesterol Efflux	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)]. If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).

Secondary Outcomes

Measure	Description	Time Frame
Psoriasis Activity (PASI and PGA)	Change in psoriasis activity will be assessed using the following standardized measurement tools for psoriasis: Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA). PASI combines the assessment of the severity of lesions and the area affected into a single score with range 0 (no disease) to 72 maximal disease. The PGA is an average assessment of all psoriatic lesions based on erythema, scale, and induration with score range 0 (no disease/clear) to 5 (maximal disease). If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Males and females 18 years of age and older.
Subject completed the VIP Study
Subject willing and able to avoid prolonged exposure of skin affected by psoriasis to natural or sunlight or tanning beds during the course of the study
Subject is willing and able to avoid topical or systemic prescription treatments for psoriasis besides adalimumab during the course of the study
Women are eligible to participate in the study if they meet one of the following criteria:
1. Women of childbearing potential must undergo pregnancy testing during the baseline visit and agree to use one of the following methods of contraception throughout the 13-month study:
  - Oral contraceptives;
  - Transdermal contraceptives
  - Injectable or implantable methods
  - Intrauterine devices
  - Barrier methods (for example but not limited to a diaphragm with spermicide, condom with spermicide); or
  - Vasectomized partner
  - Subjects using oral or parental forms of contraceptives must have been using those methods of birth control for at least three months prior to the baseline visit.
2. Women who have undergone tubal ligation
3. Women who are postmenopausal (for at least one year), sterile, or hysterectomized are eligible to participate
4. Women who agree to be sexually abstinent, defined as total abstinence from sexual intercourse, as a form of contraception are eligible to participate in the study.
Subject 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.
Able and willing to give written informed consent and to comply with requirements of this study protocol.

Exclusion Criteria:

Previous adverse event following exposure to a TNF-alpha antagonist that led to discontinuation of the TNF inhibitor and contraindicates future treatment.
Previous lack of response to a TNF-alpha antagonist led to discontinuation.
Diagnosis of erythrodermic psoriasis, generalized pustular psoriasis, or medication-induced or medication-exacerbated psoriasis.
Diagnosis of other active skin diseases or skin infections (bacterial, fungal, or viral) that may interfere with evaluation of psoriasis.
Subject is taking or requires oral or injectable corticosteroids during the study. Inhaled corticosteroids for stable medical conditions are allowed.
Poorly controlled medical condition, such as unstable ischemic heart disease, congestive heart failure, recent cerebrovascular accidents, psychiatric disease requiring frequent hospitalization, and any other condition, which, in the opinion of the Investigator, would put the subject at risk by participation in the study.
History of diabetes mellitus, type 1 or type 2 (patients with type 2 diabetes may be enrolled if the duration of diabetes is <10 years and HbA1c is <7.0%)
Uncontrolled hypertension, with measured systolic blood pressure >180 mmHg or diastolic blood pressure >90 mmHg
History of demyelinating diseases or lupus.
Subject has infection or risk factors for severe infections, for example:
- 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;
- Evidence of latent TB infection demonstrated by Purified Protein Derivative (PPD) ≥ 5 mm of induration or positive Quantiferon-GOLD results as determined within 6 months of the baseline visit for VIP-E; except if prophylactic treatment for TB, as recommended by local guidelines, is initiated prior to administration of study drug or if there is documentation that the subject has received prophylactic treatment for TB previously.
- Any other significant infection requiring hospitalization or intravenous (IV) antibiotics in the month prior to Baseline;
- Infection requiring treatment with oral or parenteral antibiotics within 14 days prior to Baseline;
- Subject will require a live vaccination during study participation including up to 30 days after the last dose of study drug.
Subject has history of hematological or solid malignancy within the past five years other than successfully treated basal cell carcinoma, non-metastatic cutaneous squamous cell carcinoma or cervical carcinoma in situ.
Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study.
Clinic laboratory analyses showing any of the following abnormal results:
- Hemoglobin (Hgb) < 10 g/dL in females or <12 g/dL in males;
- White blood cell (WBC) count <2.5 x 109/L
  - Subject can be included if WBC count is <2.5 x x 109/L and absolute neutrophil count (ANC) is >1000 cells / mm3.
- WBC count > 15 x 109/L;
- Platelet count < 100 x 109/L;
- Serum aspartate transaminase (AST) or alanine transaminase (ALT) >2.5 upper limits of normal (ULN);
- Serum total bilirubin ≥2 mg/dL (≥26 µmol/L)
Recent history of substance abuse or psychiatric illness that could preclude compliance with the protocol.
If subject is on cholesterol-lowering medication (e.g. statin), dose and form of medication must be stable for 90 days prior to baseline and remain stable throughout the duration of the study.

Contacts/Locations Module

Name	Affiliation	Role
Joel M Gelfand, MD MSCE	University of Pennsylvania	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of California, Davis Health System		Sacramento	California	95816	United States
University of Colorado

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
29776990	Derived	Mehta NN, Shin DB, Joshi AA, Dey AK, Armstrong AW, Duffin KC, Fuxench ZC, Harrington CL, Hubbard RA, Kalb RE, Menter A, Rader DJ, Reilly MP, Simpson EL, Takeshita J, Torigian DA, Werner TJ, Troxel AB, Tyring SK, Vanderbeek SB, Van Voorhees AS, Playford MP, Ahlman MA, Alavi A, Gelfand JM. Effect of 2 Psoriasis Treatments on Vascular Inflammation and Novel Inflammatory Cardiovascular Biomarkers: A Randomized Placebo-Controlled Trial. Circ Cardiovasc Imaging. 2018 Jun;11(6):e007394. doi: 10.1161/CIRCIMAGING.117.007394.

IPD Sharing Statement Module

No data available

No data is available for this block.

Arm/Group Information

ID	Title	Description
FG000	Single-Arm, Open-label Extension Trial	Single-arm, open label extension trial to continue treatment with Humira (Adalimumab) subcutaneous injection 80mg initial dose followed by 40mg maintenance dose every other week for up to 52 weeks. Adalimumab: Study participants will receive the FDA-approved dosing schedule for Adalimumab (Humira): an initial dose of 80mg followed by a 40mg maintenance dose every other week up to 52 weeks.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Single-Arm, Open-label Extension Trial	Single-arm, open label extension trial to continue treatment with Humira (Adalimumab) subcutaneous injection 80mg initial dose followed by 40mg maintenance dose every other week for up to 52 weeks. Adalimumab: Study participants will receive the FDA-approved dosing schedule for Adalimumab (Humira): an initial dose of 80mg followed by a 40mg maintenance dose every other week up to 52 weeks.

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 Vascular Inflammation

Change in total vascular inflammation of five aortic segments as assessed on FDG-PET/CT between week 52 of the adalimumab treatment period and baseline scans (prior to randomization in the VIP Trial). The arterial uptake of FDG is measured by the standardized uptake value (SUV) max divided by the venous SUIV mean yielding a target to background ration (TBR). If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).

Posted

Number

95% Confidence Interval

percentage change

52 weeks (continuation group) or 64 weeks (crossover group)

ID	Title	Description
OG000	Single-Arm, Open-label Extension Trial	Single-arm, open label extension trial to continue treatment with Humira (Adalimumab) subcutaneous injection 80mg initial dose followed by 40mg maintenance dose every other week for up to 52 weeks. Adalimumab: Study participants will receive the FDA-approved dosing schedule for Adalimumab (Humira): an initial dose of 80mg followed by a 40mg maintenance dose every other week up to 52 weeks.

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	Single-Arm, Open-label Extension Trial	Single-arm, open label extension trial to continue treatment with Humira (Adalimumab) subcutaneous injection 80mg initial dose followed by 40mg maintenance dose every other week for up to 52 weeks. Adalimumab: Study participants will receive the FDA-approved dosing schedule for Adalimumab (Humira): an initial dose of 80mg followed by a 40mg maintenance dose every other week up to 52 weeks.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
syncope	General disorders	MedDRA (10.0)	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
upper respiratory infection	Infections and infestations	MedDRA (10.0)	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Suzette Baez VanderBeek, MPH	University of Pennsylvania	2156623514		suzette.baezvanderbeek@uphs.upenn.edu

Submission Tracking

No data available

No data is available for this block.

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
D000068879	Adalimumab

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins

Masking Info

Single-Arm, open-label extension trial

EG0001 events1 affected81 at risk

EG00011 events11 affected81 at risk