Safety and Efficacy of EDP1815 in the Treatment of Patients Hospitalized With COVID-19 Infection

Study Overview
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Brief Summary
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Evelo will investigate the safety and efficacy of EDP1815 in the treatment of patients hospitalized with SARS-CoV-2 Infection

Detailed Description
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This is a randomized, placebo-controlled clinical study to assess the safety and efficacy of EDP1815 in patients hospitalized with COVID-19 infection. The study is designed to evaluate the efficacy of EDP1815 at reducing time to resolution of symptoms, preventing progression of COVID-19 symptoms and preventing COVID-Related Complications (CRC)

Official Title
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A Phase 2 Double-blind Placebo-controlled Study Investigating the Safety and Efficacy of EDP1815 in the Treatment of Patients Hospitalized With SARS-CoV-2 Infection

Conditions
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Covid19

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: Hospitalized within the last 36 hours. Receiving any form of supplementary oxygen therapy at baseline. Confirmed COVID-19 viral infection by RTPCR at screening. Age: 18-65 years old, OR >65 year-olds can be included after Data Monitoring Committee (DMC) approval Key Exclusion Criteria: Contraindications/hypersensitivity to P histicola or any of the capsule excipients Patients with chronic hypoxia or underlying significant chronic respiratory disease (such as Chronic Obstructive Pulmonary Disease (COPD), Pulmonary Fibrosis, or Bronchiectasis). Admission to ICU at time of screening. Mechanically ventilated, on continuous positive airway pressure (CPAP), or on non-invasive ventilation at the time of screening. Patient is taking a systemic immunosuppressive agent such as, but not limited to, oral steroids, methotrexate, azathioprine, ciclosporin, or tacrolimus, unless these are given as part of COVID standard of care treatment. Patient has a diagnosed primary immunodeficiency. Patient has a diagnosis of HIV/AIDS Patient has pre-existing known chronic kidney disease stage 4 or 5 or requiring renal replacement therapy (i.e. estimated glomerular filtration rate (eGFR) <30ml/min/1.73m2) Patient has pre-existing known significant liver disease with Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 5.0 x upper limit of normal (ULN) Patient has pre-existing known significant gastrointestinal tract disease expected to affect absorption within the small intestine (e.g. short bowel syndrome, inflammatory bowel disease affecting the small intestine, gastroparesis); or prior malabsorptive bariatric surgery that could interfere with GI delivery and transit time. GI signs or symptoms equivalent to CTCAE v5.0, gastrointestinal disorders, grade 3 or 4 event. Patient has pre-existing known substantially impaired cardiac function or pre-existing clinically significant cardiac diseases, including unstable angina or acute myocardial infarction ≤ 6 weeks prior to Screening. Currently participating in an interventional clinical trial (observational studies allowed). Moribund at time of screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Patients will be randomized to either the active (EDP1815) or placebo group (1:1 randomization), in addition to standard of care. Dosing will be initiated on a twice daily regime for the first 3 days (6 doses) and then once daily for the remaining 11 days (14 days total treatment course).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EDP1815<br>Patients will receive EDP1815 in addition to standard of care | Drug: EDP1815<br>* EDP1815 is an orally administered monoclonal microbe<br>|
| Placebo Comparator: Placebo<br>Patients will receive placebo in addition to standard of care | 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 |
| --- | --- | --- |
| Change From Baseline to the Lowest S/F Oxygen Ratio in Days 1 to 14 | Worst pulmonary function as measured by the change in Oxygen Saturation (SpO2) / Fraction of Inspired Oxygen (FiO2) [S/F ratio] | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in S/F Ratio | The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using change in S/F ratio at days 4, 7, 10 and 14/discharge day. | 14 days | 
| Percentage Change in S/F Ratio | The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage change in S/F ratio at days 4, 7, 10 and 14/discharge day. | 14 days | 
| Percentage of Participants at Each Level on the WHO OSCI Score | The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage of participants at each level on the WHO OSCI score at days 4, 7, 14, 21 and 42. (WHO OSCI - World health Organization, Ordinal Scale for Clinical Improvement; 0=unifected - 8=death) | 42 days | 
| Percentage of Participants With Shifts From Each Level of the WHO OSCI Score at Baseline | The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage of participants with shifts from each level of the WHO OSCI score at baseline at days 4, 7, 14, 21 and 42. (WHO OSCI - World health Organization, Ordinal Scale for Clinical Improvement; 0=uninfected - 8=death) | 42 days | 
| Number of Participants Remaining at Their Baseline Score on the WHO OSCI (or Lower) | The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage of participants remaining at their baseline score on the WHO OSCI (or lower) at days 4, 7, 14, 21 and 42. Once a participant has increased their WHO OSCI score they are not considered to have remained at or below their baseline value at future visits regardless of whether their score returns to or below their baseline value. (WHO OSCI - World health Organization, Ordinal Scale for Clinical Improvement; 0=uninfected - 8=death) | 42 days | 
| Percentage of Participants Reporting Each Level of the WHO OSCI Score at Their Worst Post-baseline Day | The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage of participants reporting each level of the WHO OSCI score at their worst post-baseline day. (WHO OSCI - World health Organization, Ordinal Scale for Clinical Improvement; 0=uninfected - 8=death) | 42 days | 
| The Time in Days Spent at Each Participant's Worst Reported WHO OSCI Score (Excluding Death). | The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using the time in days spent at each participant's worst reported WHO OSCI score (excluding death). | 42 days | 
| Intubation and Mechanical-ventilation Free Survival | The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using the intubation and mechanical-ventilation free survival, defined as the time in days from start of treatment to first occurrence of a WHO OSCI score of 6 or more. (WHO OSCI - World health Organization, Ordinal Scale for Clinical Improvement; 0=uninfected - 8=death) | 42 days | 
| Overall Survival | The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using overall survival, defined as the time in days from start of treatment to death by any cause | 42 days | 
| Number of Days Requiring Oxygen Therapy | The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using number of days requiring oxygen therapy | 42 days | 
| Number of Days With Pyrexia | The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using number of days with pyrexia ≥ 38C | 42 days | 
| Maximum Daily Temperature | The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using maximum daily temperature | 42 days | 
| SpO2 Level | The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using minimum and maximum SpO2 levels | 42 days | 
| Time to Discharge | The effect of EDP1815 on length of hospitalization and recovery in participants with COVID-19 will be measured using time to discharge, defined as the time in days from start of treatment to first occurrence of a WHO OSCI score of 2 or less. | 42 days | 
| Time to Oxygen Saturation (SpO2) ≥94% | The effect of EDP1815 on length of hospitalization and recovery in participants with COVID-19 will be measured using time to oxygen saturation (SpO2) ≥94% on room air without further requirement for oxygen therapy. | 42 days | 
| Time to Recovery | The effect of EDP1815 on length of hospitalization and recovery in participants with COVID-19 will be measured using time to recovery, defined as the time in days from symptom onset to alleviation of all COVID-19 symptoms. | 42 days | 
| Number of Participants Experiencing AEs by Seriousness and Relationship to Treatment | The safety and tolerability of EDP1815 in participants with COVID-19 will be measured using the number of participants experiencing AEs by relationship to treatment | 42 days | 
| Incidence of Clinically Significant Abnormal Lab Parameters | The safety and tolerability of EDP1815 in participants with COVID-19 will be measured using the number of participants experiencing clinically significant abnormal changes in safety lab parameters | 42 days | 
| Number of Participants Experiencing AEs by Seriousness and Relationship to Treatment | The safety and tolerability of EDP1815 in participants with COVID-19 will be measured using the number of participants experiencing AEs by seriousness | 42 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, corona virus, coronavirus, corona