Efficacy and Safety Study of HRO350 in Patients With Mild-to-moderate Psoriasis (the 'HeROPA' Study).

Overview

HRO350 contains an oil-based extract from herring roe (Clupea harengus) in soft capsules and contains phospholipids (complex lipids) which are naturally rich in marine polyunsaturated fatty acids. All the lipids in HRO350 are natural components of the human diet. It is not fully known how HRO350 exerts its effects, however there are indications that it might have a modulatory effect on the inflammatory processes involved in causing psoriasis. The study is a randomised, double-blind, placebo controlled, dose finding, multi-centre, phase 2B study. Approximately 519 patients will be participating in the UK, Norway, Germany, Finland and Poland. Patients will receive either 1050mg or 2100mg HRO0350 daily, or placebo for up to 52 weeks and will be followed up for a further 8 weeks.

Description

This study is a phase 2 multi-national (Norway, Germany, Finland, Poland and the UK), multi-centre (approx 66 sites), randomised, and placebo-controlled study assessing the dose, efficacy and safety of HRO350 in patients with mild-to-moderate psoriasis.

HRO350 contains phospholipids (complex lipids) which are naturally rich in marine polyunsaturated fatty acids that come from herring roe. All the lipids in HRO350 are natural components of the human diet. It is not fully known how HRO350 exerts its effects, however there are indications that it might have a modulatory effect on the inflammatory processes involved in causing psoriasis. There are limited treatment options available for patients with mild-to-moderate psoriasis that provide treatment satisfaction and an improvement in quality of life.

Therefore, the purpose of this study is to investigate the efficacy and safety of HRO350 in patients with mild to moderate psoriasis and help decide which doses should be included for further testing to provide the 'best' or optimal effects of HR0350.

Approximately 519 patients with mild-to-moderate psoriasis will be included in this study. The screening visit will include a review of the eligibility for the study, a physical examination, review of vital signs and blood and urine samples collected as part of the safety assessment along with assessment of their psoriasis severity.

Daily treatment will begin with 3 capsules of either HRO350 or placebo taken in the morning and 3 capsules of either HRO350 or placebo taken in the evening for up to 52 weeks. The patients will be asked to attend the clinic for a total of 8 visits and will receive 8 phone calls for safety checks and assessment of psoriasis severity. The total length of participation will be up to 60 weeks including an 8 week follow-up period.

Eligibility

Inclusion Criteria:

1. Signed and dated informed consent.
2. Males or females ≥18 years of age.
3. Diagnosis of chronic, active plaque psoriasis of mild to moderate severity since at least 6 months prior to screening.
4. Psoriasis Area and Severity Index (PASI) score ≥ 3 and ≤ 10 at screening and baseline
5. Body Surface Area (BSA) ≥ 3 at screening and baseline
6. Static Physician's Global Assessment (sPGA) ≥ 2 and ≤ 4 at screening and baseline.
7. Males, and females of child-bearing potential1, must be willing to use highly effective methods of birth control during the study period and until 30 days after end of treatment. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. Such methods include:
   • Combined (oestrogen and progestogen containing hormonal contraception associated with inhibition of ovulation -oral

     -intravaginal

     • transdermal
   • progestogen-only hormonal contraception associated with inhibition of ovulation

     -oral

     • injectable
     • implantable
   • intrauterine device
   • intrauterine hormone-releasing system
   • bilateral tubal occlusion
   • vasectomized partner
   • sexual abstinence (if this is the preferred and usual lifestyle of the patient)
     1. Female patients will be considered to be of childbearing potential as per the Clinical Trial Facilitation Group (CTFG) definition of woman of childbearing potential: Fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy (HRT). However, in the absence of 12 months of amenorrhea, confirmation with more than one FSH measurement is required.

Exclusion Criteria:

1. Diagnosis of other psoriasis clinical subtypes such as guttate, erythrodermic or pustular psoriasis.
2. Phototherapy [(i.e., ultraviolet radiation (UVB), psoralens and long-wave ultraviolet radiation (PUVA)] within 8 weeks of randomisation and during the trial.
3. Any investigational drug administered within 4 weeks of randomisation or <5 times half-lives, whichever is the longer, and during the trial.
4. Systemic anti-psoriatic treatment last 3 months (for biologics last 6 months) before randomisation or during the trial.
5. Topical anti-psoriatic treatment last 2 weeks before randomisation.
6. Any change in anti-inflammatory medication (for other chronic diseases than psoriasis) last 4 weeks before randomisation and during the trial.
7. Any intake of omega-3 fatty acid supplements or medicines last 2 weeks before randomisation and during the trial.
8. Known fish or vegetable oil (including soy) allergy, or allergy to other ingredients in the study medication, placebo or rescue medication.
9. Baseline white blood cell count <3.0x109/L or lymphocyte count <1.0x109/L, or other pathological results identified during a complete blood count, which in the opinion of the investigator may preclude the patient being enrolled.
10. Previous malignancies (except for non-melanoma skin cancer).
11. Symptomatic coronary or cerebral vascular disease.
12. Known congestive heart failure Grade IV by the New York Heart Association
13. Myocardial infarction within 6 months prior to signing the ICF
14. Onset of unstable angina within 6 months prior to signing the ICF
15. Chronic kidney disease as evidenced by a calculated glomerular filtration rate (GFR) < 60ml/min/1.73m2 at screening.
16. Abnormal liver function tests defined by:
    1. AST (SGOT), ALT (SGPT) or alkaline phosphatase (ALP) >3x the upper limit of the normal range (ULN). Elevated gamma-GT (GGT) values exceeding >3x ULN are allowed but these GGT cases will be carefully assessed alongside other clinical and laboratory data by the investigator. q. History of severe gastrointestinal problems. r. Ongoing, active infectious disease. s. Known human immunodeficiency virus (HIV)-positive status or suffering from any other immunosuppressive disease. t. History of major psychiatric illness that could interfere with the conduct of the study.
    2. Patients with documented or suspected, clinically significant, alcohol (i.e., > 12g/d for women and 24 g/d for men) or drug abuse within the past 12 months.
    3. Any other significant, unstable medical condition that would interfere with the completion of the study or interpretation of results.
    4. Women of child-bearing potential* must have a negative serum pregnancy test at Visit 1 (Screening) and a negative urine pregnancy test at Visit 2 (Baseline). x. Females who are pregnant, breast feeding, refuse to use birth control methods or who wish to become pregnant during the study period.
    5. Unable to comply with the requirements of the study or who in the opinion of the investigator is unable to comply with the requirements of the study.