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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Cardiometabolic Syndrome, Psoriasis, Inflammation, Coronary Artery Disease

Intervention / Treatment
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* Drug: Orticumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Treatment<br>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<br>* A human recombinant monoclonal antibody against a specific oxidized low-density lipoprotein (oxLDL) epitope<br>* Other names: MLDL1278a; BI-204; Anti-oxLDL Antibody;|
| Placebo Comparator: Placebo<br>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<br>* Placebo for orticumab, containing all components of formulation except the active ingredient<br>|

What is the study measuring?
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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 |