Study to Evaluate Efficacy and Safety of MP1032 in Patients With Chronic Plaque Psoriasis

A Phase II, Multicenter, Double-blind, Placebo-controlled, Efficacy and Safety Trial of Two Oral Doses (150 mg Bid / 300 mg Bid) of MP1032 in Male and Female Patients With Moderate-to-Severe Chronic Plaque Psoriasis

The primary objective of this trial is to evaluate the clinical efficacy and safety of two oral doses of MP1032 (150 mg bid and 300 mg bid) when taken for 12 weeks by patients with moderate-to-severe chronic plaque psoriasis.

This trial is a randomized, double-blind, parallel, placebo-controlled trial to evaluate the efficacy and safety of two oral doses of MP1032 (150 mg bid and 300 mg bid) in adult patients with moderate-to-severe chronic plaque psoriasis.

The trial design consists of a 28-day screening period, a 12-week treatment period, and subsequently a 28-day follow-up period. Each patient will have 6 visits and unscheduled visits as needed.

Approximately 150 patients (2 × 50 patients MP1032 and 50 patients placebo) who meet the entry criteria will be randomized on Day 1 to receive either 150 mg MP1032, 300 mg MP1032 or placebo orally twice daily for 12 weeks. The administration of IMP will stop after end of study (in max. 13 weeks).

PASI (Psoriasis Area and Severity Index), PGA (Physician Global Assessment) and BSA (Body Surface Area) Scores will be recorded at predefined timepoints as basis for the efficacy evaluation.

Safety parameter will be monitored from the signing of the informed consent form (ICF) until the last follow-up visit.

To evaluate systemic concentrations of MP1032 PK (pharmacokinetics) samples will be analyzed in a subgroup.

Inclusion Criteria:

1. Participants legally competent to sign and give informed consent.

2. Adult male and female patients between 18 years and 70 years with moderate-to-severe chronic plaque psoriasis (diagnosed by Investigator):

   1. PASI score ≥10 - ≤20 at baseline
   2. BSA score: > 10%
   3. Stable disease duration of ≥ 6 months at the initiation of IMP.
   4. topical therapy fails to control the disease

3. Body Mass Index (BMI) between 18.5 and 34.9 kg/m2.

4. Women of childbearing potential (WCBP) must have a negative serum pregnancy test at Screening (Visit 1). In addition, sexually active WCBP must agree to use adequate contraception throughout the trial (see Section 3.2 for more details on adequate contraception):

   1. A method with less than 1% failure rate OR
   2. Abstinence

5. Post-menopausal women with spontaneous amenorrhea for at least 12 months and women on hormonal replacement therapy (HRT). The use of hormonal replacement therapy (HRT) during the trial is permitted, however for these patients an appropriate contraception method according to Inclusion Criterion 4 must be ensured. Sterilized women may be included (see Section 3.2 for more details on sterile definition)

6. Male patients who are sexually active with a female partner and are not surgically sterile (vasectomy performed at least six months prior to treatment) must agree to inform their female sexual partner to use an acceptable form of birth control as described in the informed consent form. For females, an acceptable method (Pearl Index < 1%) would be to use implants, injectable, combined oral contraceptives, some intrauterine devices, or be postmenopausal, be surgically sterile (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy)

7. In good health as judged by the investigator, based on medical history, physical examination, serum chemistry, hematology and urinalysis

8. Patients must meet the following clinical laboratory criteria:

   • White blood cell count ≥3.5 × 109/L
   • Platelet count ≥100 × 109/L
   • Serum creatinine ≤1.5 × upper limit of normal (ULN); estimated glomerular filtration rate >60 mL/min
   • Total bilirubin ≤1.5 × ULN
   • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN
   • Hemoglobin ≥ lower limit of normal as per central laboratory reference ranges for women and men accordingly
   • No coagulopathy (International Normalized Ratio [INR] <1.5)

9. Patients agree to minimize normal sun exposure during the course of the trial

10. Patients are considered reliable and capable of adhering to the protocol (e.g. able to understand the patient information and complete diaries), visit schedule, or medication intake according to the judgment of the Investigator.

Exclusion Criteria:

1. Patients with non-plaque form of psoriasis (erythrodermic, guttate, pustular form of psoriasis). Associated psoriasis arthritis is allowed provided no other in-/exclusion criteria are influenced, no forbidden concomitant therapy is required for the well -being of the patient and there is no impact on trial objectives as determined by the Investigator.
2. Treatment with concomitant medication that may affect and provoke or aggravate psoriasis, e.g. antimalarial drugs, beta-blockers or ACE (angiotensin-converting-enzyme) inhibitors unless on a stable dose for 3 months before IMP intake.
3. Evidence of skin conditions at the time of Screening Visit other than psoriasis that would interfere with evaluations of the effect of the IMP on psoriasis.
4. Patients with any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the ICF, as assessed by the investigator.
5. Pregnant or lactating women or women planning to become pregnant during the trial and / or within 28 days following the last dose of IMP.
6. Male patients planning a partner pregnancy or sperm donation during the trial including follow up period.
7. Known allergies to any ingredient of the IMP e.g. mannitol, macrophage modulators, or gelatin.
8. History or symptoms of a clinically significant illness in the four weeks before first treatment and during the trial that in the opinion of the investigator may place the patient at risk by trial participation or influence the outcome of the trial. Well controlled diseases such as hypertension, hyperlipidemia, diabetes or hypothyroidism are permitted.
9. Patients with active malignancy or history of malignancy, except for basal cell and actinic keratosis. Basal cell carcinoma of the skin or in situ cervical carcinoma that have been fully treated and show no evidence of recurrence are allowed.
10. Positive HIV-Antibody, HBs-Antigen or HCV-Antibody-Test at screening.
11. Previous strong sun exposure (e.g. sea holiday) within 28 days or UV treatment within 24 weeks before IMP initiation.
12. Known photo allergy and / or experienced drug-induced photo toxicity.
13. Elective (planned) hospitalization or medical intervention preventing patient from following the protocol requirements.
14. Prior treatment not adhering to defined drug classes and related washout periods (Protocol table 2.)
15. Planned use of any ultraviolet (UV) phototherapy or photochemotherapy / photosensitizing drugs during the course of the trial and within 28 days/24 weeks following the last dose of the IMP.
16. Patients with a history of chronic alcohol or drug abuse within 6 months of IMP initiation.
17. Patients with a blood pressure outside the given range of 160 mm Hg (systolic) and 95 mm Hg (diastolic)
18. Patients who are employed by MetrioPharm, contract research organization (CRO) or clinical site involved in the clinical trial.
19. Vulnerable patients (e.g. patients kept in detention).
20. Patients who are unable to communicate, read or understand the local language, or who display another condition, which, in the Investigator's opinion, makes them unsuitable for clinical trial participation.
21. Patient is institutionalized because of legal or regulatory order.