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

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

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Inflammation; Psoriasis; Cardiometabolic Syndrome
• Intervention / Treatment: Drug: Orticumab; Drug: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85260
      • CCT- Research at the center for Dermatology and Plastic Surgery
  • California
    • Santa Monica, California, United States, 90404
      • Derm Institute & Skin Care Ctr., Inc.
    • Tustin, California, United States, 92780
      • Orange County Research Center
    • Vista, California, United States, 92083
      • Blue Coast Research Center
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Dawes Fretzin Clinical Research Group, LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Excel Clinical Research
    • Las Vegas, Nevada, United States, 89030
      • Las Vegas Clinical Trials
  • Oklahoma
    • Tulsa, Oklahoma, United States, 85260
      • Vital Prospects Clinical Research Institute, PC
  • Texas
    • Mesquite, Texas, United States, 75149
      • SMS Clinical Research
    • San Antonio, Texas, United States, 78218
      • Texas Dermatology and Laser Specialists
    • Webster, Texas, United States, 77598
      • Center for Clinical Studies, LTD.LLP
  • Utah
    • Springville, Utah, United States, 84663
      • CCT Research - Springville Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Treatment; Dosage: Repeating intravenous dose. Administered by infusion over 30 minutes. Frequency and duration: once weekly x 4 weeks, then once monthly x 2 months.	Drug: Orticumab; A human recombinant monoclonal antibody against a specific oxidized low-density lipoprotein (oxLDL) epitope; Other Names: MLDL1278a; BI-204; Anti-oxLDL Antibody
Placebo Comparator: Placebo; Dosage: Repeating intravenous dose. Administered by infusion over 30 minutes. Frequency and duration: once weekly x 4 weeks, then once monthly x 2 months.	Drug: Placebo; Placebo for orticumab, containing all components of formulation except the active ingredient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
Incidence of Treatment Emergent Adverse Events (TEAEs)		106 days (Week 15)
Incidence of serious adverse events (SAEs)		106 days (Week 15)
Incidence of abnormal hemodynamic parameters	heart rate (HR) and blood pressure (BP)	Weeks 3, 7, 11 and 15
Incidence of abnormal laboratory tests results		Weeks 3 and 15
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
Change in coronary artery plaque burden by CCTA	Change in total, noncalcified and low attenuation coronary artery plaque volume	106 days (Week 15)

Collaborators and Investigators

• Sponsor: Abcentra
• Investigators: Principal Investigator: Joel Neutel, MD, Orange County Research Center

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2021
• Primary Completion (Actual): November 11, 2022
• Study Completion (Actual): November 11, 2022

Study Registration Dates

• First Submitted: February 16, 2021
• First Submitted That Met QC Criteria: February 25, 2021
• First Posted (Actual): March 2, 2021

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Skin Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Skin Diseases, Papulosquamous; Insulin Resistance; Hyperinsulinism; Coronary Disease; Coronary Artery Disease; Inflammation; Psoriasis; Metabolic Syndrome
• Other Study ID Numbers: Ort-2020-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No