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
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Psoriasis
- Sponsor
- MetrioPharm AG
- Enrollment
- 155
- Locations
- 19
- Primary Endpoint
- PASI 75 - Week 12 (EoT)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants legally competent to sign and give informed consent.
- •Adult male and female patients between 18 years and 70 years with moderate-to-severe chronic plaque psoriasis (diagnosed by Investigator):
- •PASI score ≥10 - ≤20 at baseline
- •BSA score: \> 10%
- •Stable disease duration of ≥ 6 months at the initiation of IMP.
- •topical therapy fails to control the disease
- •Body Mass Index (BMI) between 18.5 and 34.9 kg/m
- •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):
- •A method with less than 1% failure rate OR
- •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)
Exclusion Criteria
- •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.
- •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.
- •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.
- •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.
- •Pregnant or lactating women or women planning to become pregnant during the trial and / or within 28 days following the last dose of IMP.
- •Male patients planning a partner pregnancy or sperm donation during the trial including follow up period.
- •Known allergies to any ingredient of the IMP e.g. mannitol, macrophage modulators, or gelatin.
- •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.
- •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.
- •Positive HIV-Antibody, HBs-Antigen or HCV-Antibody-Test at screening.
Arms & Interventions
Placebo bid
6 × placebo hard gelatin capsules (per dosage) are provided twice daily over a period of 12 weeks.
Intervention: Placebo
150 mg MP1032 bid
3 × 50 mg (150 mg) MP1032 plus 3 × placebo hard gelatin capsules (per dosage) are provided twice daily over a period of 12 weeks.
Intervention: MP1032
150 mg MP1032 bid
3 × 50 mg (150 mg) MP1032 plus 3 × placebo hard gelatin capsules (per dosage) are provided twice daily over a period of 12 weeks.
Intervention: Placebo
300 mg MP1032 bid
6 × 50 mg (300 mg) MP1032 hard gelatin capsules (per dosage) are provided twice daily over a period of 12 weeks.
Intervention: MP1032
Outcomes
Primary Outcomes
PASI 75 - Week 12 (EoT)
Time Frame: Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up)
Percentage of patients reaching PASI 75 in treatment groups (150 and 300 mg bid) compared to placebo. The PASI (psoriasis area severity index) is the most commonly used and validated assessment for grading the severity of psoriasis in clinical studies and combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease) wherein any value higher than 10 is considered as moderate to severe psoriasis. The number of responders corresponds to the number of patients with an improvement of at least 75% in the PASI score at End-of-Treatment (EoT) compared to baseline.
PGA Improvement - Week 12 (EoT)
Time Frame: Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up)
PGA improvement rate in treatment groups (150 and 300 mg bid) compared to placebo. The PGA (Physician's global assessment) provides an overall evaluation of the severity of the disease ranging from 0 (clear skin - no diseases) to 6 (severe disease). The number of responders corresponds to the number of patients with an improvement of 1 or more points on the 7-points PGA scale at End-of-Treatment (EoT) compared to baseline.
Secondary Outcomes
- PASI 75 VCS - Week 12 (EoT)(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PGA Improvement VCS - Week 12 (EoT)(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PASI 50 - Week 12 (EoT)(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PASI ANCOVA Change From Baseline - Week 12 (EoT)(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PASI Descriptive Statistics - Week 12 (EoT)(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- Time to PASI 75(from treatment start (Study Day 1 - Baseline) to either Study Day 25, 56, 84 (EoT) or 112 (FU))
- Time to PASI 50(from treatment start (Study Day 1 - Baseline) to either Study Day 25, 56, 84 (EoT) or 112 (FU))
- PGA Descriptive Statistics - Week 12 (EoT)(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PGA Frequency Counts - Week 12 (EoT)(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- BSA Descriptive Statistics - Week 12 (EoT)(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PASI 75 - Week 4(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PASI 75 - Week 8(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PASI 75 - Week 16 (FU)(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PASI 50 - Week 4(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PASI 50 - Week 8(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PASI 50 - Week 16 (FU)(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PASI ANCOVA Change From Baseline - Week 4(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PASI ANCOVA Change From Baseline - Week 8(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PASI ANCOVA Change From Baseline - Week 16 (FU)(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PASI Descriptive Statistics - Week 4(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PASI Descriptive Statistics - Week 8(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PASI Descriptive Statistics - Week 16 (FU)(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PGA Improvement - Week 4(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PGA Improvement - Week 8(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PGA Improvement - Week 16 (FU)(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PGA Descriptive Statistics - Week 4(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PGA Descriptive Statistics - Week 8(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PGA Descriptive Statistics - Week 16 (FU)(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PGA Frequency Counts - Day 1 (Baseline)(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PGA Frequency Counts - Week 4(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PGA Frequency Counts - Week 8(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PGA Frequency Counts - Week 16 (FU)(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- BSA Descriptive Statistics - Week 4(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- BSA Descriptive Statistics - Week 8(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- BSA Descriptive Statistics - Week 16 (FU)(Scoring took place on Site visits: Day1 (Baseline), Week 4, Week 8, Week 12 (End-of-Treatment), Week 16 (Follow-Up))
- PK Data - Cmax(Morning dose on Study Day 1)
- PK Data - Tmax(Morning dose on Study Day 1)
- PK Data - AUC(0,t)(Morning dose on Study Day 1)
- Number of Patients With TEAEs(Overall Trial - Explicit inquiry on Day1, Week 4, Week 8, Week 12 (EoT), Week 16 (Follow Up))
- Number of Patients With Serious TEAEs(Overall Trial - Explicit inquiry on Day1, Week 4, Week 8, Week 12 (EoT), Week 16 (Follow Up))
- Number of Patients With TEAEs Leading to Study Discontinuation(Overall Trial - Explicit inquiry on Day1, Week 4, Week 8, Week 12 (EoT), Week 16 (Follow Up))
- Number of Patients With TEAEs by SOC(Overall Trial - Explicit inquiry on Day1, Week 4, Week 8, Week 12 (EoT), Week 16 (Follow Up))
- Number of Patients With TEAEs by Intensity(Overall Trial - Explicit inquiry on Day1, Week 4, Week 8, Week 12 (EoT), Week 16 (Follow Up))
- Number of Patients With TEAEs by Relation to the IMP(Overall Trial - Explicit inquiry on Day1, Week 4, Week 8, Week 12 (EoT), Week 16 (Follow Up))
- Number of Patients With TEAEs by Causality With the IMP(Overall Trial - Explicit inquiry on Day1, Week 4, Week 8, Week 12 (EoT), Week 16 (Follow Up))
- Extent of Exposure - Dosed Capsules(overall trial / treatment period - cumulative from baseline to week 12 (EoT) or - if applicable - week16 (FU))
- Extent of Exposure - Capsules Per Application(overall trial / treatment period - from baseline to week 12 (EoT) or - if applicable - week16 (FU))
- Extent of Exposure - Capsules Per Day(overall trial / treatment period - from baseline to week 12 (EoT) or - if applicable - week16 (FU))
- Sufficient Extent of Exposure(overall trial / treatment period - cumulative from baseline to week 12 (EoT) or - if applicable - week16 (FU))
- Extent of Exposure - Treatment Duration(overall trial / treatment period - cumulative from baseline to week 4, 8, 12 (EoT), and - if applicable - week16 (FU))