Study to Evaluate Safety and Efficacy of Oral MP1032 in Psoriasis Patients
Condition: Psoriasis; Plaque Psoriasis
MeSH terms: Psoriasis
Intervention: MP1032; Placebo
Intervention description: hard gelatine capsules containing 50 mg MP1032 as active ingredient; hard gelatine capsules without active ingredient
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Plaque psoriasis; chronic; moderate; severe; Plaque

Summary:

      This Phase IIa study is designed to assess the safety, tolerability and pharmacokinetics of
      oral MP1032 in patients with moderate to severe psoriasis over a period of 6 weeks. Secondary
      endpoints to evaluate clinical parameters for psoriasis during the 6 week treatment period
      and a 4-week follow up will provide an opportunity to perform a first assessment of oral
      MP1032's clinical efficacy in the treatment of moderate to severe psoriasis.

      The study population will consist of 44 enrolled (40 completed) patients with moderate to
      severe chronic plaque psoriasis. Patients must be able to provide written consent and meet
      all the inclusion criteria and none of the exclusion criteria.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Participants legally competent to sign and give informed consent.

          2. Adult male and female patients aged 18 to 65 years with chronic plaque psoriasis:

               1. PASI score > 10 at screening and

               2. Disease duration of ≥ 6 months at the initiation of study medication.

          3. Body Mass Index (BMI) between 18.5 and 34.9 kg/m2.

          4. Diagnosis of chronic plaque psoriasis confirmed by a dermatologist/physician.

          5. Women of childbearing potential (WCBP) must have a negative urine pregnancy test at
             Screening (Visit 1). In addition, sexually active WCBP must agree to use 2 forms of
             adequate contraception throughout the trial.

          6. Post-menopausal women with spontaneous amenorrhea for at least 12 months and serum
             levels follicle stimulating hormone (FSH) Levels indicating post-menopausal state as
             per local laboratory reference ranges. Females on hormone replacement therapy (HRT)
             and whose menopausal status is in doubt must discontinue HRT to allow confirmation of
             post-menopausal status prior to study enrollment. For most forms of HRT, at least 2 to
             4 weeks will elapse between the cessation of therapy and the blood draw; this interval
             depends on the type and dosage of HRT. Following confirmation of their post-menopausal
             status, they can resume use of HRT during the study. Sterilized women may be included.

          7. Patients must meet the following clinical laboratory criteria:

               1. White blood cell count ≥ 3.5 x 10^9/L

               2. Platelet count ≥ 100 x 10^9/L

               3. Serum creatinine ≤ 1.5 x upper limit of normal (ULN); estimated glomerular
                  filtration rate > 60 mL/min

               4. Total bilirubin ≤ 1.5 x ULN

               5. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 1.5 x ULN

               6. Hemoglobin ≥ lower limit of normal as per local laboratory reference ranges for
                  women and men accordingly

               7. No coagulopathy (International Normalized Ratio [INR] < 1.5).

          8. Patients agree not to increase normal sun exposure during the course of the study.

          9. Patients are able to swallow 2 small capsules during each administration.

         10. Patients are considered reliable and capable of adhering to the protocol (eg, able to
             understand 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 or palmo
             plantar psoriasis; severe form of psoriasis arthritis, inverse form of psoriasis).
             Mild to moderate cases of psoriasis arthritis are allowed provided there is no impact
             on study objectives as determined by the Investigator.

          2. Patients with drug-induced psoriasis.

          3. Evidence of skin conditions at the time of screening visit other than psoriasis that
             would interfere with evaluations of the effect of study medication on psoriasis.

          4. Patients with any serious medical condition, laboratory abnormality, or psychiatric
             illness that would prevent the patient from signing the informed consent form.

          5. Pregnant or lactating females or females planning to become pregnant during the study
             and/or within 28 days following the last dose of study medication.

          6. Male patients planning a partner pregnancy or sperm donation during the study or
             within 3 months following the last dose of study medication.

          7. Known allergies to mannitol, macrophage modulators, and gelatin.

          8. Patients with a recent history or current signs or symptoms, as determined by the
             Investigator, of severe, progressive viral or bacterial infections, of clinically
             significant cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic,
             renal, hematologic, immunologic insufficiency disease (excluding psoriasis) requiring
             systemic treatment or other major diseases, which are not well controlled and may
             interfere with the conduct of the trial.

          9. Patients with active malignancy or history of malignancy, except for basal cell or
             squamous cell carcinoma and actinic keratosis. Basal cell carcinoma and small squamous
             cell carcinoma of the skin which have been excised according to guidelines within the
             last 5 years or in situ cervical carcinoma that has been fully treated and shows no
             evidence of recurrence are allowed.

         10. Clinically significant abnormality on 12-lead electrocardiogram (ECG) at screening.

         11. Positive human immunodeficiency virus (HIV), hepatitis B or hepatitis C laboratory
             result.

         12. Previous strong sun exposure (eg, sea holiday) within the 28 days before study
             medication initiation.

         13. Known photo allergy and/or experienced drug-induced photo toxicity.

         14. Elective (planned) hospitalization or medical intervention preventing patient from
             following the protocol requirements.

         15. Prior Treatment: Drug class >> Last dose prior to study medication initiation (washout
             period)

             Topical psoriasis medications (including, but not limited to corticosteroids,
             calcipotriene, topical vitamin D derivates, retinoids, coal tar) >> 14 days

             Topical immunosuppressive drugs (tacrolimus, pimecrolimus, or anthralin) >> 14 days
             (Exception: Non-medicated emollients, moisturizers and sunscreens will be allowed),
             Use of low potency topical steroids for critical areas such as the face, genitalia,
             and scalp may be allowed until 24 hours prior to randomization.

             Systemic treatment (non-biologic): Systemic immunosuppressant agents (eg:
             methotrexate, cyclosporine, azathioprine), Systemic fumarate, Systemic corticosteroids
             >> 28 days

             Phototherapy or photochemotherapy/photosensitizing drugs >> 28 days

             Systemic retinoids >> 12 weeks

             Any investigational drug >> 24 weeks (systemic); 4 weeks (topical)

             Any Anti-TNFs: Infliximab, adalimumab, golimumab, etanercept, etc. >> 12 weeks

             Other Biologics and other systemic therapies: ustekinumab, alefacept, apremilast,
             Efalizumab, certolizumab pegol, secukinumab, etc. >> 24 weeks

             Rituximab >> 12 months

         16. Drinking or ingesting grapefruit, pomegranate, grapefruit juice or grapefruit
             containing products within 14 days of study medication initiation.

         17. Planned use of any ultraviolet (UV) phototherapy or photochemotherapy/photosensitizing
             drugs during the course of the study and within 28 days following the last dose of the
             study medication.

         18. Patients with a history of chronic alcohol or drug abuse within 6 months of study
             medication initiation.

         19. Patients employed by MetrioPharm or a contract research organization (CRO) involved in
             the clinical study.

         20. Vulnerable patients (eg, patients kept in detention).

         21. Patients who are unable to communicate, read and understand the local language, or who
             display any other condition, which, in the Investigator's opinion, makes them
             unsuitable for clinical study participation.