| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate-to-severe plaque-type psoriasis |
|
| E.1.1.1 | Medical condition in easily understood language |
| Moderate-to-severe plaque-type psoriasis |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10071117 |
| E.1.2 | Term | Plaque psoriasis |
| E.1.2 | System Organ Class | 100000004858 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective is to evaluate the efficacy and safety of a modified-release orismilast tablet versus placebo in adults with moderate-to-severe plaque-type psoriasis. |
|
| E.2.2 | Secondary objectives of the trial |
| Evaluate the dose response of orismilast and identify the dose with the best benefit/risk ratio to be evaluated in a Phase 3 program. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in the protocol.
2. Male and female patients ≥18 years of age at the time of signing the ICF.
3. Body weight of >40 kg at the time of signing the ICF.
4. Diagnosis of chronic, stable plaque-type psoriasis at least 2 months before the Screening visit. If the patient is diagnosed with psoriasis arthritis, the arthritis should be stable.
5. Moderate-to-severe plaque-type psoriasis as defined by PASI ≥12, BSA ≥10%, and IGA ≥3 at the screening and baseline visits.
6. Candidate for systemic antipsoriatic treatment or phototherapy.
7. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at the Screening visit and a negative urine pregnancy test at the Baseline visit. In addition, sexually active WOCBP must agree to use a highly effective method of contraception until at least 4 weeks after the end of study treatment. Highly effective methods of contraception are those that have a failure rate of <1% (when implemented consistently and correctly) and include hormonal contraceptives (combined oral contraceptive, patch, vaginal ring, injectable, or implantable); progestogen-only hormonal contraception associated with inhibition of ovulation (administration may be oral, injectable, or implantable); intrauterine devices or systems; self or partner vasectomy; or bilateral tubal ligation. Patients must have been on a stable dose of hormonal contraceptives for at least 4 weeks before the Baseline visit. Abstinence from heterosexual intercourse is an accepted method of contraception if it is the patient’s lifestyle and is practiced for the entire duration of the study. Note: A woman of nonchildbearing potential is defined as a woman with surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or a woman in a postmenopausal status defined as cessation of menses for at least 12 months without an alternative medical cause and a confirmatory follicle-stimulating hormone (FSH) test or as cessation of menses for at least 24 months without an alternative medical cause. |
|
| E.4 | Principal exclusion criteria |
1. Therapy-resistant psoriasis defined as ≥2 treatment failures due to
inadequate efficacy within the past 5 years of any biologic therapies
(including but not limited to etanercept, adalimumab, infliximab,
certolizumab pegol, guselkumab, secukinumab, risankizumab,
ixekizumab, tildrakizumab, or ustekinumab) administered in adequate
dose and duration according to the label or local/national guidelines
(patients who stopped systemic treatment for reasons not related to lack
of efficacy are not excluded).
2. Unstable psoriasis or psoriatic arthritis (PsA) with acute deterioration
within 4 weeks of the Screening visit.
3. History of allergy or hypersensitivity to any component of the study
treatment.
4. Active infection (eg, bacteria, viral, fungal) requiring treatment with
systemic antibiotics within 4 weeks of the Screening visit.
5. Malignancy or history of malignancy except for treated (ie, cured)
basal cell skin carcinomas.
6. Current diagnosis of predominant guttate, erythrodermic, exfoliative,
or pustular psoriasis, or of drug-induced psoriasis, or other skin
conditions that might confound the evaluation of psoriasis vulgaris, as
judged by the Investigator (eg, atopic dermatitis, lupus).
7. Any recurrent medical condition associated with serious
gastrointestinal diseases, such as inflammatory bowel disease.
8. Any medical or psychiatric condition (eg, current major depression
with a score for depressive symptoms ≥15 of Hospital Anxiety and
Depression Scale at Baseline, schizophrenia, suicidal behavior,
psychiatric hospitalization within the prior year) which, in the
Investigator's opinion, would preclude the patient from adhering to the
protocol, completing the study per protocol, and/or would place the
patient at unacceptable risk for receiving the investigational therapy.
9. Any therapies and systemic treatments as described in Table 3 of
Clinical Study Protocol which do not comply with the indicated washout
interval.
10. Any previous treatment with orismilast or failure of treatment with
apremilast or any other systemic phosphodiesterase-4 (PDE4) inhibitor
as described in Table 3 of Clinical Study Protocol.
11. Any condition, including laboratory or ECG abnormalities, that places
the patient at unacceptable risk to participate in the study or confounds
the ability to interpret data from the study.
12. Severe hepatic impairment based upon medical history and
laboratory abnormalities (eg, low albumin and abnormal bilirubin).
13. Any of the following abnormalities in clinical laboratory tests at
Screening, as assessed by the study-specific laboratory and confirmed by
a single repeat, if deemed necessary:
a. Absolute neutrophil count of <3.0 × 10^9/L (<3000/mm^3)
b. Hemoglobin of <10.0 g/dL or hematocrit <30%
c. Platelet count of <100 × 10^3 cells/mm^3 (SI: <100 × 10^9 cells/L).
d. Absolute lymphocyte count of <1.0 × 10^9/L (<1000/mm^3)
e. Total bilirubin >1.5 × the upper limit of normal (ULN); patients with a
history of Gilbert's syndrome may have a direct bilirubin measured and
would be eligible for this study provided the direct bilirubin is ≤ULN;
f. Alanine aminotransferase or aspartate aminotransferase >2.5 × the
ULN;
g. Serum creatinine ≥1.5 mg/dL. For a patient with a value of ≥1.5
mg/dL, a creatinine clearance of ≥60 mL/min (calculated using the CKDEPI
Creatinine Equation) is allowed.
14. History or evidence of hepatitis B virus (HBV) infection at Screening.
Patients with positive hepatitis B surface antigen (HBsAg) are excluded.
For patients with isolated positive antihepatitis B core antibody (HBcAb),
hepatitis B surface antibody (HBsAb) result must also be positive to be
considered for this study.
15. History or positive test result for hepatitis C virus (HCV) antibody,
indicating ongoing infection, at Screening. Confirmatory testing for HCV
RNA will be conducted for patients who have a positive test result.
Patients who have a negative result for HCV RNA will be eligible to
participate in the study.
16. History of positive HIV, or have congenital or acquired
immunodeficiency (eg, common variable immunodeficiency disease).
Patients who are positive for HIV antibodies (HIV-1 or HIV-2) at
Screening are excluded from the study.
17. Suicidal ideation or behavior in the past 12 months as indicated by a
positive response (yes) to questions 4 or 5 on the C-SSRS completed at
the Screening visit or the C-SSRS completed at the Baseline visit.
18. Pregnant or breastfeeding.
19. History of alcohol or substance abuse within 6 months before
Baseline that, in the opinion of the Investigator, will preclude
participation in the study.
20. Institutionalized by court order or by local authority. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint in this study is the percentage change in Psoriasis Activity and Severity Index (PASI) score from Baseline at Week 16. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| As specified in the endpoints. |
|
| E.5.2 | Secondary end point(s) |
Key Secondary Endpoints:
• Patients achieving 75% reduction in PASI (PASI75) response at Week 16.
• Patients achieving a score of Clear (0) or Almost Clear (1) and an at least 2-point improvement in Investigator Global Assessment (IGA) at Week 16.
Other Secondary Endpoints:
• Patients achieving a score of Clear (0) or Almost Clear (1) and an at least 2-point improvement in IGA at Weeks 4, 8, 12, and 20.
• Patients achieving PASI75 response at Weeks 4, 8, 12, and 20.
• Patients achieving 50% reduction in PASI (PASI50) and 90% reduction in PASI (PASI90) response at Weeks 4, 8, 12, 16, and 20.
• Change from Baseline in PASI at Weeks 4, 8, 12, and 20.
• Change from Baseline in total Psoriasis Symptoms Scale (PSS) score at Weeks 4, 8, 12, 16, and 20.
• Change from Baseline in each individual item of the PSS at Weeks 4, 8, 12, 16, and 20.
• Change from Baseline in the affected body surface area (BSA) at Weeks 4, 8, 12, 16, and 20.
• Change from Baseline in Dermatology Life Quality Index (DLQI) score at Weeks 16 and 20.
• Patients experiencing psoriasis rebound by Week 20, defined as PASI ≥125% of Baseline or new generalized pustular, erythrodermic, or more inflammatory psoriasis. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| As specified in the endpoints. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 34 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| United States |
| Poland |
| Germany |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 16 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 16 |
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