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

• ClinicalTrials.gov Identifier: NCT04776629
• Recruitment Status: Active, not recruiting
• First Posted: March 2, 2021
• Last Update Posted: September 10, 2022
• Sponsor: Abcentra
• Information provided by (Responsible Party): Abcentra

Tracking Information

• First Submitted Date: February 16, 2021
• First Posted Date: March 2, 2021
• Last Update Posted Date: September 10, 2022
• Actual Study Start Date: June 30, 2021
• Estimated Primary Completion Date: October 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 25, 2021)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 25, 2021)

• 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)
• 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
• 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.
• 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).
• 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'.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: February 25, 2021)

• 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)
• 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

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: A Proof-of-Activity Study With Orticumab in Subjects With Psoriasis and Cardiometabolic Risk Factors
• 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
• 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.

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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Psoriasis
• Inflammation
• Coronary Artery Disease
• Cardiometabolic Syndrome

Intervention

• Drug: Orticumab
  A human recombinant monoclonal antibody against a specific oxidized low-density lipoprotein (oxLDL) epitope
  Other Name: MLDL1278a; BI-204; Anti-oxLDL Antibody
• Drug: Placebo
  Placebo for orticumab, containing all components of formulation except the active ingredient

Study Arms

• 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.

  Intervention: Drug: Orticumab
• 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.

  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 8, 2022): 77
• Original Estimated Enrollment (submitted: February 25, 2021): 75
• Estimated Study Completion Date: February 2023
• Estimated Primary Completion Date: October 2022 (Final data collection date for primary outcome measure)

Eligibility 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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04776629
• Other Study ID Numbers: Ort-2020-01
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Abcentra
• Original Responsible Party: Same as current
• Current Study Sponsor: Abcentra
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Joel Neutel, MD; Orange County Research Center

• PRS Account: Abcentra
• Verification Date: September 2022