A Proof-of-Activity Study With Orticumab in Subjects With Psoriasis and Cardiometabolic Risk Factors

Coronary Artery Disease Clinical Trial

Official title:

A Multi-Center, Randomized, Double-Blind, Placebo-controlled Proof-of-Activity Study With Orticumab in Subjects With Moderate-to-Severe Psoriasis and Cardiometabolic Risk Factors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04776629
• Other study ID #: Ort-2020-01
• Status: Completed
• Phase: Phase 2
• Start date: June 30, 2021
• Est. completion date: November 11, 2022

Study information

• Verified date: February 2024
• Source: Abcentra
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of this proof-of-activity, phase 2 trial is to evaluate the safety and activity of orticumab in subjects with moderate to severe psoriasis and cardiometabolic risk factors.

Description:

This randomized, double-blind, study is designed to compare the effect of orticumab against placebo in subjects with moderate to severe psoriasis and cardiometabolic risk factors. A total of 75 subjects will be randomized in a double-blind fashion to receive intravenous (IV) infusions either of orticumab or placebo for up to 78 days. Participants will be enrolled into one of the two groups: active treatment or placebo. Subjects will be randomized in a 2:1 ratio, orticumab to placebo and receive up to 11 weeks of treatment. Planned treatments are weekly x 4 , then monthly x 2 . The Internal Safety Review Committee (ISRC) will review the blinded safety data after the first subject completes the first dose (Day 1), the first five subjects complete the first dose (Day 1), and the first ten subjects complete the first dose (Day 1). The IRSC will review all adverse reactions to all administered doses at these times.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: November 11, 2022
• Est. primary completion date: November 11, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

Inclusion criteria:

• Stable/chronic plaque psoriasis with PASI score of = 12 AND involving = 10% of the subject's BSA.- = 30 years of age at time of consent.
• BMI = 30 kg/m2
• LDL = 100 mg/dL at Screening.
• All females must have a negative serum pregnancy test result at Screening and a negative urine pregnancy test prior to dosing. Exclusion Criteria:

Subjects are excluded from the study if any of the following criteria are met:

• Past use of orticumab.
• Any of the nonplaque forms of psoriasis: erythrodermic, guttate, or pustular.
• Scalp, palmar or plantar psoriasis only, at Screening or Baseline.
• Have evidence of skin conditions (e.g., eczema) at the time of Screening or Baseline visit that would interfere with theevaluation of psoriasis.
• Newly discovered Type 2 diabetes mellitus (T2DM)
• Moderate or high-intensity statin use or new use of a low-intensity statin therapy.
• No use of anti-coagulating or anti-thrombotic agents.
• Poorly controlled hypertension
• Use of an IL-23 blocker in the past 180 days, an IL-17 blocker in the past 16 weeks, or a TNF blocker in the past 12 weeks.
• Use of methotrexate, cyclosporine, or apremilast in the past 4 weeks.
• History of hypersensitivity or allergies to any contents in the orticumab formulation.
• A history of any clinically important abnormalities in cardiac rhythm or conduction.
• A history of prolonged QT intervals or a family history of long QT-syndrome at Screening.
• A history of first, second or third-degree atrioventricular (AV) block, or AV dissociation.
• A history of complete bundle branch block.
• Unstable angina pectoris, myocardial infarction, transient ischemic attack, or stroke within 3 months prior to Screening, or participants who have undergone percutaneous coronary intervention or a coronary artery bypass graft within 6 months prior to Screening or who are due to undergo these procedures at the time of Screening.
• Severe congestive heart failure (NYHA III or IV).

Related Conditions & MeSH terms

• Cardiometabolic Syndrome
• Coronary Artery Disease
• Inflammation
• Metabolic Syndrome
• Psoriasis

Intervention

Drug:
• Orticumab
A human recombinant monoclonal antibody against a specific oxidized low-density lipoprotein (oxLDL) epitope
• Placebo
Placebo for orticumab, containing all components of formulation except the active ingredient

Locations

Country	Name	City	State
United States	Dawes Fretzin Clinical Research Group, LLC	Indianapolis	Indiana
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Excel Clinical Research	Las Vegas	Nevada
United States	Las Vegas Clinical Trials	Las Vegas	Nevada
United States	SMS Clinical Research	Mesquite	Texas
United States	Texas Dermatology and Laser Specialists	San Antonio	Texas
United States	Derm Institute & Skin Care Ctr., Inc.	Santa Monica	California
United States	CCT- Research at the center for Dermatology and Plastic Surgery	Scottsdale	Arizona
United States	CCT Research - Springville Dermatology	Springville	Utah
United States	Vital Prospects Clinical Research Institute, PC	Tulsa	Oklahoma
United States	Orange County Research Center	Tustin	California
United States	Blue Coast Research Center	Vista	California
United States	Center for Clinical Studies, LTD.LLP	Webster	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Abcentra

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Coronary Artery Inflammation by CCTA	Change in coronary artery perivascular fat attenuation index (FAI) measured by coronary computed tomographic angiography (CCTA)	106 days (Week 15)
Other	Change in coronary artery plaque burden by CCTA	Change in total, noncalcified and low attenuation coronary artery plaque volume	106 days (Week 15)
Primary	Mean percent change from Baseline in Psoriasis Area Severity Index (PASI)	PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease)	106 days (Week 15)
Primary	Percentage of participants achieving treatment success by the 5-point static Investigator's Global Assessment modified 2011 version (sIGA) Score	Percentage of participants achieving treatment success (clear =0 or almost clear =1) and greater than or equal to (>=) 2 Point Improvement at Week 15 on the sIGA scale	106 days (Week 15)
Primary	Incidence of Treatment Emergent Adverse Events (TEAEs)		106 days (Week 15)
Primary	Incidence of serious adverse events (SAEs)		106 days (Week 15)
Primary	Incidence of abnormal hemodynamic parameters	heart rate (HR) and blood pressure (BP)	Weeks 3, 7, 11 and 15
Primary	Incidence of abnormal laboratory tests results		Weeks 3 and 15
Primary	Incidence of abnormal physical examination findings	Physical examination will include the following organ or body system assessments: general appearance; eyes; ears, nose, and throat; head and neck; chest and lungs; cardiovascular; abdomen; musculoskeletal; lymphatic; dermatological; neurological; and extremities.	Weeks 3, 7, 11, 15
Secondary	Mean percent change from Baseline in Psoriasis Area Severity Index (PASI)	PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease)	Weeks 1, 3, 7, and 11
Secondary	Percentage of Participants achieving PASI75 and PASI50	PASI75 is a 75 percent reduction in PASI score. PASI50 is a 50 percent reduction in PASI score	Weeks 1, 3, 7, and 11
Secondary	Mean percent change in Baseline in Body Surface Area (BSA) % involvement	Minimum: 0 percent, Maximum: 100 percent. Higher percentage indicates more skin with psoriasis.	Weeks 1, 3, 7, 11, 15
Secondary	Mean change from Baseline in Dermatology Life Quality Index (DLQI) score	DLQI is a ten-question questionnaire used to measure the impact of skin disease on the quality of life of an affected person. Each question is scored from 0 to 3, giving a possible score range from 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life).	Weeks 3, 7, 11, 15
Secondary	Mean change from Baseline in Itch Numerical Rating Scale (INRS) Score	The Itch NRS is a self-administered subject reported outcome questionnaire that is completed during protocol specified clinic visits. Participants indicate itch severity by circling the integer that best describes the worst level of itching due to psoriasis in the past 24 h on an 11-point scale anchored at 0, representing 'no itching' and 10, representing 'worst itch imaginable'.	Weeks 3 and 15