A Phase 2b Study of the Efficacy, Safety, and Tolerability of M1095 (Sonelokimab) in Subjects With Moderate to Severe Psoriasis

Study Overview
=================
Brief Summary
-----------------
This is a multi-center phase 2b study in subjects with moderate to severe chronic plaque-type psoriasis. Approximately 300 subjects will be enrolled at approximately 60 investigator sites in North America and Europe.

Official Title
-----------------
A Phase 2b Randomized, Double-blind, Placebo Controlled, Multi-center 12-week Study With an Additional 40-week Follow-up Assessment of Efficacy, Safety and Tolerability of M1095 in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis

Conditions
-----------------
Psoriasis

Intervention / Treatment
-----------------
* Drug: M1095 (Sonelokimab)
* Drug: Placebo
* Drug: Secukinumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female subjects between 18 and 75 years of age. Moderate to severe plaque-type psoriasis for at least 6 months. Subject is a candidate for systemic biologic therapy. Subject has IGA ≥3, involved body surface area (BSA) ≥10%, and PASI ≥12 at screening and at baseline. Subject is able to comply with the study procedures. Subject must provide informed consent. Exclusion Criteria (Main): Non-plaque type psoriasis, drug-induced psoriasis, or other skin conditions (e.g., eczema). (Psoriatic arthritis is allowed). Other medical conditions, including planned surgery or active infection / history of infection, as defined in the study protocol. Subjects will be screened for tuberculosis and hepatitis B / hepatitis C. Laboratory abnormalities at screening, as defined in the study protocol. Prior use of systemic or topical treatments for psoriasis, as defined in the study protocol. Prior use of any compound targeting IL-17, more than two biologic therapies, ustekinumab within 6 months, or TNF targeting therapies within 12 weeks. History of suicidal thoughts within 12 months.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: M1095 (Sonelokimab) 30mg<br>M1095, 30 mg, given at Week 0, 2, 4, 8, 12 and every four weeks. | Drug: M1095 (Sonelokimab)<br>* M1095 (Sonelokimab) is a trivalent monomeric nanobody® that neutralizes interleukins IL-17A, IL-17F, and IL-17A/F.<br>* Other names: Sonelokimab;|
| Experimental: M1095 (Sonelokimab) 60mg<br>M1095, 60 mg, given at Week 0, 2, 4, 8, 12 and every four weeks. | Drug: M1095 (Sonelokimab)<br>* M1095 (Sonelokimab) is a trivalent monomeric nanobody® that neutralizes interleukins IL-17A, IL-17F, and IL-17A/F.<br>* Other names: Sonelokimab;|
| Experimental: M1095 (Sonelokimab) 120mg - regimen 1<br>M1095, 120 mg, given at Week 0, 2, 4, 8, 12 and every eight weeks. | Drug: M1095 (Sonelokimab)<br>* M1095 (Sonelokimab) is a trivalent monomeric nanobody® that neutralizes interleukins IL-17A, IL-17F, and IL-17A/F.<br>* Other names: Sonelokimab;|
| Experimental: M1095 (Sonelokimab) 120mg - regimen 2<br>M1095, 120 mg, given at Week 0, 2, 4, 6, 8, 10, 12 and every four weeks. | Drug: M1095 (Sonelokimab)<br>* M1095 (Sonelokimab) is a trivalent monomeric nanobody® that neutralizes interleukins IL-17A, IL-17F, and IL-17A/F.<br>* Other names: Sonelokimab;|
| Placebo Comparator: Placebo / M1095 (Sonelokimab) 120mg<br>Placebo, given at Week 0, 1, 2, 3, 4, 6, 8 and 10, then M1095, 120mg, given at Week 12, 14, 16, and every four weeks. | Drug: M1095 (Sonelokimab)<br>* M1095 (Sonelokimab) is a trivalent monomeric nanobody® that neutralizes interleukins IL-17A, IL-17F, and IL-17A/F.<br>* Other names: Sonelokimab;Drug: Placebo<br>* Placebo contains no active drug.<br>|
| Active Comparator: Secukinumab<br>Secukinumab, 300mg, given at Week 0, 1, 2, 3, 4, 8, 12 and every four weeks. | Drug: Secukinumab<br>* Secukinumab is a human immunoglobulin G1 (IgG1) monoclonal antibody that selectively binds IL-17A.<br>* Other names: Cosentyx®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With an Investigator's Global Assessment (IGA) Score of 0 or 1 | The primary endpoint is achievement of an IGA score of 0 or 1 at Week 12, with an IGA reduction of at least 2 points from baseline. The percentage of subjects in the Intent to Treat (ITT) Analysis Set with an IGA score of 0 or 1 at Week 12 will be used to compare treatment arms. IGA is the Investigator's Global Assessment of the extent of psoriasis, with 0 = clear of psoriasis, 1 = almost clear, 2 = mild psoriasis, 3 = moderate psoriasis, and 4 = severe psoriasis (the worst assessment on this scale). Higher scores in the IGA indicate a worse outcome. | Week 12, as compared to Week 0 (baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 100% (i.e. Clear of Psoriasis) | PASI 100, i.e. a subject's psoriasis has completely cleared at Week 12, compared to baseline. | Week 12, as compared to Week 0 (baseline) | 
| Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 90% (i.e. a 90% Improvement in Psoriasis) | PASI 90, i.e. a subject's psoriasis has cleared by 90% at Week 12, compared to baseline | Week 12, as compared to baseline | 
| Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 75% (i.e. a 75% Improvement in Psoriasis) | PASI 75, i.e. a subject's psoriasis has cleared by 75% at Week 12, compared to baseline | Week 12, as compared to Week 0 (baseline) |