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

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ClinicalTrials.gov Identifier: NCT04776629
Recruitment Status : Not yet recruiting
First Posted : March 2, 2021
Last Update Posted : March 2, 2021
Sponsor:
Information provided by (Responsible Party):
Abcentra

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.

Condition or disease Intervention/treatment Phase
Psoriasis Inflammation Coronary Artery Disease Cardiometabolic Syndrome Drug: Orticumab Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Estimated Study Start Date : March 2021
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Psoriasis

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 Name: 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




Primary Outcome Measures :
  1. Mean percent change from Baseline in Psoriasis Area Severity Index (PASI) [ Time Frame: 106 days (Week 15) ]
    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)

  2. Percentage of participants achieving treatment success by the 5-point static Investigator's Global Assessment modified 2011 version (sIGA) Score [ Time Frame: 106 days (Week 15) ]
    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

  3. Incidence of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 106 days (Week 15) ]
  4. Incidence of serious adverse events (SAEs) [ Time Frame: 106 days (Week 15) ]
  5. Incidence of abnormal hemodynamic parameters [ Time Frame: Weeks 3, 7, 11 and 15 ]
    heart rate (HR) and blood pressure (BP)

  6. Incidence of abnormal laboratory tests results [ Time Frame: Weeks 3 and 15 ]
  7. Incidence of abnormal physical examination findings [ Time Frame: Weeks 3, 7, 11, 15 ]
    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.


Secondary Outcome Measures :
  1. Mean percent change from Baseline in Psoriasis Area Severity Index (PASI) [ Time Frame: Weeks 1, 3, 7, and 11 ]
    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)

  2. Percentage of Participants achieving PASI75 and PASI50 [ Time Frame: Weeks 1, 3, 7, and 11 ]
    PASI75 is a 75 percent reduction in PASI score. PASI50 is a 50 percent reduction in PASI score

  3. Mean percent change in Baseline in Body Surface Area (BSA) % involvement [ Time Frame: Weeks 1, 3, 7, 11, 15 ]
    Minimum: 0 percent, Maximum: 100 percent. Higher percentage indicates more skin with psoriasis.

  4. Mean change from Baseline in Dermatology Life Quality Index (DLQI) score [ Time Frame: Weeks 3, 7, 11, 15 ]
    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).

  5. Mean change from Baseline in Itch Numerical Rating Scale (INRS) Score [ Time Frame: Weeks 3 and 15 ]
    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'.


Other Outcome Measures:
  1. Change in Coronary Artery Inflammation by CCTA [ Time Frame: 106 days (Week 15) ]
    Change in coronary artery perivascular fat attenuation index (FAI) measured by coronary computed tomographic angiography (CCTA)

  2. Change in coronary artery plaque burden by CCTA [ Time Frame: 106 days (Week 15) ]
    Change in total, noncalcified and low attenuation coronary artery plaque volume



Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).
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Responsible Party: Abcentra
ClinicalTrials.gov Identifier: NCT04776629    
Other Study ID Numbers: Ort-2020-01
First Posted: March 2, 2021    Key Record Dates
Last Update Posted: March 2, 2021
Last Verified: February 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Coronary Artery Disease
Psoriasis
Metabolic Syndrome
Inflammation
Pathologic Processes
Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Skin Diseases, Papulosquamous
Skin Diseases
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases