Clinical trial NCT02908347: Study to Evaluate Safety and Efficacy of Oral MP1032 in Psoriasis Patients
Official title: A Randomized (1:1), Double-blind, Parallel, Placebo-controlled Exploratory Pilot Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Systemic (po) Application of MP1032 in Patients With Moderate to Severe Chronic Plaque Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Psoriasis
Plaque Psoriasis
Keywords: Plaque psoriasis
chronic
moderate
severe
Plaque
Lead sponsor: MetrioPharm AG
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2016-09-20
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: This study is a randomized, double-blind, parallel, placebo-controlled exploratory pilot study to evaluate safety, pharmacokinetics and efficacy of systemic oral (po) administration of 100 mg MP1032 bid in adult patients with moderate to severe chronic plaque psoriasis.

The study design consists of a 28-day screening/run-in period, a 42-day treatment period, 1 day for the End of Treatment visit, and a 28-day follow-up period. Forty-four patients who meet the entry criteria will be randomized on Day 1 in a 1:1 ratio to receive either 100 mg MP1032 or placebo orally twice daily for 42 days. The goal is to have 40 patients (20 in each treatment group) complete the study.

Pharmacokinetic sampling will occur on 3 designated study days. Safety will be monitored from the signing of the informed consent form (ICF) until the last follow-up visit on Day 71.

Efficacy will be assessed on 6 designated study days using the following assessments: PASI, PGA, DLQI, mNAPSI, and EQ-5D 5L (VAS).

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.

Primary outcomes:
measure: Safety - Treatment Emergent Adverse Events (TEAEs) - Number of TEAEs
timeFrame: Continuously from Treatment Start until the last follow-up visit on Study Day 71
measure: Safety - Treatment Emergent Adverse Events (TEAEs) - Number of Related TEAEs by SOC
timeFrame: Continuously from Treatment Start until the last follow-up visit on Study Day 71
measure: Safety - Treatment Emergent Adverse Events (TEAEs) - Number of Patients With TEAEs
timeFrame: Continuously from Treatment Start until the last follow-up visit on Study Day 71
measure: Safety - Treatment Emergent Adverse Events (TEAEs) - Number of Patients With Related TEAEs by SOC
timeFrame: Continuously from Treatment Start until the last follow-up visit on Study Day 71
measure: Pharmacokinetics (PK) - Plasma Concentrations
timeFrame: Study Days 1, 15, 29 and 43
measure: Pharmacokinetics (PK) - Maximum Observed Concentration (Cmax)
timeFrame: Study Day 1
measure: Pharmacokinetics (PK) - Time
timeFrame: Study Day 1
measure: Pharmacokinetics (PK) - Area Under the Curve (AUC)
timeFrame: Study Day 1
measure: Pharmacokinetics (PK) - Area Under the Curve (AUC) - Subgroups
timeFrame: Study Day 1
Secondary outcomes:
measure: Psoriasis Area Severity Index (PASI) - Observed PASI Values
timeFrame: Study Day 1, 43, 57 and 71
measure: Psoriasis Area Severity Index (PASI) - Change From Baseline
timeFrame: Study Day 1 and 43
measure: Psoriasis Area Severity Index (PASI) - PASI Percentage Change - Including Subgroup Analysis AUC2h
timeFrame: Study Day 1, 29 and 43
measure: Psoriasis Area Severity Index (PASI) - PASI Percentage Change - Including Subgroup Analysis AUCt
timeFrame: Study Day 1, 29 and 43
measure: Psoriasis Area Severity Index (PASI) - PASI 30 and PASI 50 - Number of Patients
timeFrame: Study Day 1, 29 and 43
measure: Psoriasis Area Severity Index (PASI) - PASI 30 and PASI 50 - Responder Frequency
timeFrame: Study Day 1, 29 and 43
measure: Physician's Global Assessment (PGA) - Observed Values and Change From Baseline
timeFrame: Study Day 1 and 43
measure: Dermatology Life Quality Index (DLQI) - Observed Values and Change From Baseline.
timeFrame: Study Day 1 and 43
measure: EQ-5D 5L Visual Analogue Scale (VAS)
timeFrame: Study Day 1 and 43
measure: Modified Nail Psoriasis Severity Index (mNAPSI) - Observed Values and Change From Baseline
timeFrame: Study Day 1 and 43
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Rothaar Studien GmbH
city: Berlin
country: Germany
facility: PAREXEL International GmbH, Klinikum Westend
city: Dresden
country: Germany
facility: Klinische Forschung Dresden GmbH
city: Freiburg
country: Germany
facility: Gemeinschaftspraxis Prof. Dr. Vanscheidt und Dr. Ukat
Study officials:
affiliation: Parexel
name: Anke Gauliard, MD
role: PRINCIPAL_INVESTIGATOR
References: