A Phase 2 Study Investigating the Effect of EDP1815 in the Treatment of Mild to Moderate Plaque Psoriasis

Study Overview
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Brief Summary
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This Phase 2 study has been designed to investigate the clinical safety and efficacy of EDP1815 and to identify an optimal dose in subjects with mild to moderate psoriasis.

Detailed Description
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This is a multicenter, randomized, double-blind, placebo-controlled, parallel-cohort, dose-ranging study of participants with mild to moderate plaque psoriasis. This Phase 2 study has been designed to investigate the clinical safety and efficacy of EDP1815 and to identify an optimal dose in subjects with mild to moderate psoriasis.

Official Title
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A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Cohort, Dose-Ranging Study Investigating the Effect of EDP1815 in the Treatment of Mild to Moderate Plaque Psoriasis

Conditions
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Psoriasis, Plaque Psoriasis

Intervention / Treatment
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* Drug: EDP1815
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Males or females ≥18 and ≤70 years old at the time of informed consent. A documented diagnosis of plaque psoriasis for ≥6 months. Have mild to moderate plaque psoriasis with plaque covering body surface area (BSA) of ≥3% and ≤10% and meet both of the following additional criteria: PASI score of ≥6 and ≤15, and PGA score of 2 or 3. Key Exclusion Criteria: Have a diagnosis of non-plaque psoriasis. Plaque psoriasis restricted to scalp, palms, and soles only. Have received systemic immunosuppressive therapy (MTX, apremilast, azathioprine, cyclosporine, 6-thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, and tacrolimus) within 4 weeks of first administration of study drug. Unresponsive to prior use of biologics (including, but not limited to, TNFα inhibitors, natalizumab, efalizumab, anakinra or agents that modulate B cells or T cells). If prior biologic therapy and responsive, participants must have been off therapy for at least 12 months prior to first administration of study drug. Have received phototherapy or any systemic medications/treatments that could affect psoriasis or PGA evaluation (including, but not limited to oral or injectable corticosteroids, retinoids, psoralens, sulfasalazine, hydroxyurea, or fumaric acid derivatives) within 4 weeks of first administration of study drug. This includes therapeutic doses of non-steroidal anti-inflammatory drugs such as ibuprofen, although intermittent as required use as an analgesic is permitted when required. Chronic use of low dose aspirin for cardiovascular protection is permitted. Currently receiving lithium, antimalarials, leflunomide, or IM gold, or have received lithium, antimalarials, IM gold, or leflunomide within 4 weeks of first administration of study drug. Have used topical medications/treatments that could affect psoriasis or PGA evaluation (including [but not limited to] high- and mid-potency corticosteroids, anthralin, calcipotriene, topical vitamin D derivatives, retinoids, tazarotene, methoxsalen, trimethylpsoralens, picrolimus, and tacrolimus) within 2 weeks of the first administration of study drug. Topical unmedicated emollients and low-potency topical corticosteroids are not excluded. Gastrointestinal tract disease (eg, short-bowel syndrome, diarrhea-predominant irritable bowel syndrome) that could interfere with GI delivery and transit time. Active inflammatory bowel disease. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Day 1 (Visit 2). Have received live or live attenuated replicating vaccine within 6 weeks prior to screening or intend to have such a vaccination during the study. Clinically significant abnormalities in screening laboratory values that would render a participant unsuitable for inclusion (per investigator judgment). Known history of or positive test for HIV, or active infection with hepatitis C or chronic hepatitis B. History of clinically significant acute cardiac or cerebrovascular event within 6 months before screening (includes stroke, transient ischemic attack, and coronary heart disease [angina pectoris, myocardial infarction, heart failure, revascularization procedures]). Current acute or chronic inflammatory disease other than psoriasis or psoriatic arthritis (eg, inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus). If a subject is off all treatment and is disease and has been symptom free for greater than 12 months, then the inflammatory disease is considered to be in remission and they may be enrolled. Hypersensitivity to P histicola or to any of the excipients. Active untreated mental or psychiatric disorder. Participants who are on stable dosing of medication for a mental or psychiatric disorder for at least 6 months before screening and whose treating physicians consider them to be mentally stable may be enrolled. Any major or minor GI surgery within 6 months of screening. Any major surgery within 6 months of screening. Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated. Treatment with another investigational drug, biological agent, or device within 1 month of screening, or 5 half-lives of investigational agent, whichever is longer. Initiating any OTC or prescription medication including vitamins, herbal supplements and nutraceuticals (eg, supplements including high doses of probiotics and prebiotics as usually found in capsules/tablets/powders), except acetaminophen/paracetamol and anti-histamines, within 14 days prior to baseline or anticipates change in dosage for the duration of the study period. Note that probiotic and prebiotic foods that contain low doses are allowed (eg, yoghurt, kefir, kombucha, however, supplements containing high doses of probiotics and prebiotics are not allowed at any point during the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a multicenter, randomized, double-blind, placebo-controlled, parallel-cohort, dose-ranging study of participants with mild to moderate plaque psoriasis
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>75 subjects with mild to moderate psoriasis; 50 on EDP1815, 25 on placebo. Dose = 0.8 x 10^11 cells, capsule, once daily, 16 weeks | Drug: EDP1815<br>* EDP1815 is an orally administered, pharmaceutical preparation of a single strain of bacteria<br>Drug: Placebo<br>* Placebo oral capsule<br>|
| Experimental: Cohort 2<br>75 subjects with mild to moderate psoriasis; 50 on EDP1815, 25 on placebo. Dose = 3.2 x 10^11 cells, capsule, once daily, 16 weeks | Drug: EDP1815<br>* EDP1815 is an orally administered, pharmaceutical preparation of a single strain of bacteria<br>Drug: Placebo<br>* Placebo oral capsule<br>|
| Experimental: Cohort 3<br>75 subjects with mild to moderate psoriasis; 50 on EDP1815, 25 on placebo. Dose = 8.0 x 10^11 cells, capsule, once daily, 16 weeks | Drug: EDP1815<br>* EDP1815 is an orally administered, pharmaceutical preparation of a single strain of bacteria<br>Drug: Placebo<br>* Placebo oral capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percentage Change in PASI | The Psoriasis Area and Severity Index Score (PASI) is a physician assessment that combines the assessment of the severity of and area affected by psoriasis into a single score in the range 0 (no disease) to 72 (maximal disease).The efficacy of EDP1815 will be measured using the mean percentage change in PASI from baseline to week 16. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percentage Change in PASI | The Psoriasis Area and Severity Index Score (PASI) is a physician assessment that combines the assessment of the severity of and area affected by psoriasis into a single score in the range 0 (no disease) to 72 (maximal disease). The efficacy of EDP1815 will be measured using the mean percentage change from baseline in PASI from baseline at weeks 4, 8, and 12. | 12 weeks | 
| Mean Absolute Change in PASI | The Psoriasis Area and Severity Index Score (PASI) is a physician assessment that combines the assessment of the severity of and area affected by psoriasis into a single score in the range 0 (no disease) to 72 (maximal disease). The efficacy of EDP1815 will be measured using the mean absolute change from baseline in PASI from baseline at weeks 4, 8, 12, and 16. | 16 weeks | 
| Achievement of PASI-50 | The efficacy of EDP1815 will be measured using the achievement of PASI-50 at weeks 4, 8, 12, and 16. PASI-50 is defined by at least a 50% reduction from baseline in the PASI score. | 16 weeks | 
| Time to First Achievement of PASI-50 | The efficacy of EDP1815 will be measured using the time to first achievement of PASI-50 | 20 weeks | 
| Achievement of PASI-75 | The efficacy of EDP1815 will be measured using the achievement of PASI-75 at week 16. PASI-75 response is defined by at least a 75% reduction from baseline in the PASI score. | 16 weeks | 
| Achievement of PASI-90 | The efficacy of EDP1815 will be measured using the achievement of PASI-90 at week 16.PASI-90 response is defined by at least a 90% reduction from baseline in the PASI score. | 16 weeks | 
| Achievement of PASI-100 | The efficacy of EDP1815 will be measured using the achievement of PASI-100 at week 16. PASI-100 response is defined as achieving a complete resolution of all disease. | 16 weeks | 
| Achievement of PGA of 0 or 1 With a ≥2-point Improvement From Baseline | The efficacy of EDP1815 will be measured using the achievement of PGA of 0 or 1 with a ≥2-point improvement from baseline at Week 16 [PGA = Physician's Global Assessment]. The National Psoriasis Foundation Psoriasis Score version of a PGA is calculated by averaging the total body erythema, induration, and desquamation scores. Erythema, induration, and desquamation will be scored on a 6-point scale, ranging from 0 (clear) to 5 (severe): the total PGA score is defined as the average of the erythema, induration, and desquamation scores. PGA score of 0 or 1 is defined as clear or almost clear of psoriasis. | 16 weeks | 
| Achievement of PGA of 0 | The efficacy of EDP1815 will be measured using the achievement of PGA of 0 at Week 16 [PGA = Physician's Global Assessment]. The National Psoriasis Foundation Psoriasis Score version of a PGA is calculated by averaging the total body erythema, induration, and desquamation scores. Erythema, induration, and desquamation will be scored on a 6-point scale, ranging from 0 (clear) to 5 (severe): the total PGA score is defined as the average of the erythema, induration, and desquamation scores. PGA score of 0 or 1 is defined as clear or almost clear of psoriasis. A PGA 0 is defined as clear or no signs of psoriasis. | 16 weeks | 
| Mean Percentage Change in PGAxBSA | [PGA = Physician's Global Assessment, BSA = Body Surface Area]. The National Psoriasis Foundation Psoriasis Score version of a static Physicians Global Asessment (PGA) is calculated by averaging the total body erythema, induration, and desquamation scores. Erythema, induration, and desquamation will be scored on a 6-point scale, ranging from 0 (clear) to 5 (severe): the total PGA score is defined as the average of the erythema, induration, and desquamation scores. Body surface area (BSA) measures the total area of the body affected by psoriasis. Psoriasis that occurs on less than 5 percent of the BSA is considered mild to moderate psoriasis. Psoriasis affecting more than 5 percent of the BSA is considered moderate to severe psoriasis. The efficacy of EDP1815 will be measured using the mean percentage change from baseline in PGA x BSA at Weeks 4, 8, 12, and 16. | 16 weeks | 
| Mean Absolute Change in PGAxBSA | [PGA = Physician's Global Assessment, BSA = Body Surface Area]. The National Psoriasis Foundation Psoriasis Score version of a static Physicians Global Asessment (PGA) is calculated by averaging the total body erythema, induration, and desquamation scores. Erythema, induration, and desquamation will be scored on a 6-point scale, ranging from 0 (clear) to 5 (severe): the total PGA score is defined as the average of the erythema, induration, and desquamation scores. Body surface area (BSA) measures the total area of the body affected by psoriasis. Psoriasis that occurs on less than 5 percent of the BSA is considered mild to moderate psoriasis. Psoriasis affecting more than 5 percent of the BSA is considered moderate to severe psoriasis. The efficacy of EDP1815 will be measured using the mean absolute change from baseline in PGA x BSA at Weeks 4, 8, 12, and 16. | 16 weeks | 
| Mean Percentage Change in LSS | The LSS is used to score the severity of psoriasis plaques. The dimensions of scaling, erythema, and plaque elevation are each scored on a scale from 0 (clear) to 4 (very severe), and the total LSS is the numerical sum of the 3-dimensional scores. The efficacy of EDP1815 will be measured using the mean percentage change from baseline in LSS (Lesion Severity Score) at Weeks 4, 8, 12, and 16. | 16 weeks | 
| Mean Absolute Change in LSS | The LSS is used to score the severity of psoriasis plaques. The dimensions of scaling, erythema, and plaque elevation are each scored on a scale from 0 (clear) to 4 (very severe), and the total LSS is the numerical sum of the 3-dimensional scores.The efficacy of EDP1815 will be measured using the mean absolute change from baseline in LSS (Lesion Severity Score) at Weeks 4, 8, 12, and 16. | 16 weeks | 
| Mean Percentage Change in DLQI | The DLQI is a patient reported outcomes instrument for assessing the impact of dermatologic conditions on patients' quality of life. The higher the score the more the impact on quality of life. The efficacy of EDP1815 will be measured using mean percentage change from baseline in Dermatology Life Quality Index (DLQI) at Weeks 4, 8, 12, and 16. | 16 weeks | 
| Mean Absolute Change in DLQI | The DLQI is a patient reported outcomes instrument for assessing the impact of dermatologic conditions on patients' quality of life. There are 10 questions each scored 0-3, the higher the score the more the impact on quality of life (Total score range 0-30; 0 = no impact, 30 = greatest impact).The efficacy of EDP1815 will be measured using the mean absolute change from baseline in Dermatology Life Quality Index (DLQI) at Weeks 4, 8, 12, and 16 | 16 weeks | 
| Mean Percentage Change in mNAPSI | The mNAPSI is a tool for physicians to evaluate the severity of nail bed psoriasis and nail matrix psoriasis by area of involvement in the nail unit. The higher the score the more severe the nail bed psoriasis. The efficacy of EDP1815 will be measured using the mean percentage change in mNAPSI total score (modified Nail Psoriasis Severity Index) from baseline at Weeks 4, 8, 12, and 16 | 16 weeks | 
| Mean Absolute Change in mNAPSI | The mNAPSI is a tool for physicians to evaluate the severity of nail bed psoriasis and nail matrix psoriasis by area of involvement in the nail unit. Each fingernail is rated for the presence and severity of seven features to give a total fingernail score of 0-13 (0= no involvement, 13 = greatest involvement). The total mNAPSI score is the sum of the 10 fingernail scores (range 0-130; 0= no involvement, 130= greatest involvement).The higher the score the more severe the nail bed psoriasis. The efficacy of EDP1815 will be measured using the mean absolute change in mNAPSI total score (modified Nail Psoriasis Severity Index) from baseline at Weeks 4, 8, 12, and 16 | 16 weeks | 
| Cumulative Incidence of Partial Relapse | The efficacy of EDP1815 will be measured by calculating the cumulative incidence of partial relapse at Weeks 20, 24, 28, and 40 for participants who were classified as responders at week 16. Partial relapse is defined as a loss of the PASI-50 response after week 16 and after cessation of study treatment, or commencing a new treatment for psoriasis. | 40 weeks | 
| Cumulative Incidence of Complete Relapse | The efficacy of EDP1815 will be measured by calculating the cumulative incidence of complete relapse at Weeks 20, 24, 28, and 40 in participants who were considered as responders at week 16. Relapse is defined as an increase in the severity of the psoriasis as measured by PASI to the baseline value or greater, or commencement of a new treatment for psoriasis. | 40 weeks | 
| Cumulative Incidence of Rebound | The efficacy of EDP1815 will be measured by calculating the cumulative incidence of rebound at Weeks 20, 24, 28, and 40 in participants with at least one PASI assessment after the end of treatment. Rebound is defined as an increase in the severity of the psoriasis as measured by PASI to 125% of baseline score or above, or onset of new pustular/erythrodermic psoriasis, within 3 months of cessation of study treatment. | 40 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PSO, mild psoriasis, moderate psoriasis, plaque psoriasis, psoriasis, EDP1815