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

NCT04776629 | Completed Phase 2 FDA Drug

• 1 other identifier: Ort-2020-01
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 13

Brief 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.

Conditions

Psoriasis; Inflammation; Coronary Artery Disease; Cardiometabolic Syndrome

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (5)

• Mean percent change from Baseline in Psoriasis Area Severity Index (PASI)

  Weeks 1, 3, 7, and 11

• Percentage of Participants achieving PASI75 and PASI50

  Weeks 1, 3, 7, and 11

• Mean percent change in Baseline in Body Surface Area (BSA) % involvement

  Weeks 1, 3, 7, 11, 15

• Mean change from Baseline in Dermatology Life Quality Index (DLQI) score

  Weeks 3, 7, 11, 15

• Mean change from Baseline in Itch Numerical Rating Scale (INRS) Score

  Weeks 3 and 15

Other Outcomes (2)

• Change in Coronary Artery Inflammation by CCTA

  106 days (Week 15)

• Change in coronary artery plaque burden by CCTA

  106 days (Week 15)

Study Arms (2)

Active Treatment

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Orticumab DRUG

A human recombinant monoclonal antibody against a specific oxidized low-density lipoprotein (oxLDL) epitope

Also known as: MLDL1278a; BI-204; Anti-oxLDL Antibody

Active Treatment

Placebo DRUG

Placebo for orticumab, containing all components of formulation except the active ingredient

Placebo

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Abcentra: lead

Study Sites (13)

CCT- Research at the center for Dermatology and Plastic Surgery

Scottsdale, Arizona, 85260, United States

Location

Derm Institute & Skin Care Ctr., Inc.

Santa Monica, California, 90404, United States

Location

Orange County Research Center

Tustin, California, 92780, United States

Location

Blue Coast Research Center

Vista, California, 92083, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Dawes Fretzin Clinical Research Group, LLC

Indianapolis, Indiana, 46250, United States

Location

Las Vegas Clinical Trials

Las Vegas, Nevada, 89030, United States

Location

Excel Clinical Research

Las Vegas, Nevada, 89109, United States

Location

Vital Prospects Clinical Research Institute, PC

Tulsa, Oklahoma, 85260, United States

Location

SMS Clinical Research

Mesquite, Texas, 75149, United States

Location

Texas Dermatology and Laser Specialists

San Antonio, Texas, 78218, United States

Location

Center for Clinical Studies, LTD.LLP

Webster, Texas, 77598, United States

Location

CCT Research - Springville Dermatology

Springville, Utah, 84663, United States

Location

Related Publications (1)

• Farina CJ, Davidson MH, Shah PK, Stark C, Lu W, Shirodaria C, Wright T, Antoniades CA, Nilsson J, Mehta NN. Inhibition of oxidized low-density lipoprotein with orticumab inhibits coronary inflammation and reduces residual inflammatory risk in psoriasis: a pilot randomized, double-blind placebo-controlled trial. Cardiovasc Res. 2024 May 29;120(7):678-680. doi: 10.1093/cvr/cvae057. No abstract available.

  PMID: 38523341 DERIVED

MeSH Terms

Conditions

Psoriasis; Inflammation; Coronary Artery Disease; Metabolic Syndrome

Interventions

MLDL1278A

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Joel Neutel, MD

  Orange County Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2021
• First Posted: March 2, 2021
• Study Start: June 30, 2021
• Primary Completion: November 11, 2022
• Study Completion: November 11, 2022
• Last Updated: February 2, 2024

Record last verified: 2024-02

Locations

US (13)