Clinical trial NCT04776629: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Psoriasis
Inflammation
Coronary Artery Disease
Cardiometabolic Syndrome
Lead sponsor: Abcentra
Sponsor class: INDUSTRY
First posted: 2021-03-02
Enrollment: 77
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Mean percent change from Baseline in Psoriasis Area Severity Index (PASI)
timeFrame: 106 days (Week 15)
measure: Percentage of participants achieving treatment success by the 5-point static Investigator's Global Assessment modified 2011 version (sIGA) Score
timeFrame: 106 days (Week 15)
measure: Incidence of Treatment Emergent Adverse Events (TEAEs)
timeFrame: 106 days (Week 15)
measure: Incidence of serious adverse events (SAEs)
timeFrame: 106 days (Week 15)
measure: Incidence of abnormal hemodynamic parameters
timeFrame: Weeks 3, 7, 11 and 15
measure: Incidence of abnormal laboratory tests results
timeFrame: Weeks 3 and 15
measure: Incidence of abnormal physical examination findings
timeFrame: Weeks 3, 7, 11, 15
Secondary outcomes:
measure: Mean percent change from Baseline in Psoriasis Area Severity Index (PASI)
timeFrame: Weeks 1, 3, 7, and 11
measure: Percentage of Participants achieving PASI75 and PASI50
timeFrame: Weeks 1, 3, 7, and 11
measure: Mean percent change in Baseline in Body Surface Area (BSA) % involvement
timeFrame: Weeks 1, 3, 7, 11, 15
measure: Mean change from Baseline in Dermatology Life Quality Index (DLQI) score
timeFrame: Weeks 3, 7, 11, 15
measure: Mean change from Baseline in Itch Numerical Rating Scale (INRS) Score
timeFrame: Weeks 3 and 15
Other outcomes:
measure: Change in Coronary Artery Inflammation by CCTA
timeFrame: 106 days (Week 15)
measure: Change in coronary artery plaque burden by CCTA
timeFrame: 106 days (Week 15)
Locations:
city: Scottsdale
country: United States
facility: CCT- Research at the center for Dermatology and Plastic Surgery
state: Arizona
city: Santa Monica
country: United States
facility: Derm Institute & Skin Care Ctr., Inc.
state: California
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Vista
country: United States
facility: Blue Coast Research Center
state: California
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Indianapolis
country: United States
facility: Dawes Fretzin Clinical Research Group, LLC
state: Indiana
city: Las Vegas
country: United States
facility: Las Vegas Clinical Trials
state: Nevada
city: Las Vegas
country: United States
facility: Excel Clinical Research
state: Nevada
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute, PC
state: Oklahoma
city: Mesquite
country: United States
facility: SMS Clinical Research
state: Texas
city: San Antonio
country: United States
facility: Texas Dermatology and Laser Specialists
state: Texas
city: Webster
country: United States
facility: Center for Clinical Studies, LTD.LLP
state: Texas
city: Springville
country: United States
facility: CCT Research - Springville Dermatology
state: Utah
Study officials:
affiliation: Orange County Research Center
name: Joel Neutel, MD
role: PRINCIPAL_INVESTIGATOR
References: