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

Phase 2

Terminated

• Conditions: Covid19
• Interventions: Drug: EDP1815; Drug: Placebo

• Registration Number: NCT04488575
• Lead Sponsor: Evelo Biosciences, Inc.

Brief Summary

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

Detailed Description

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)

Study Timeline

• Study First Submitted: 2020-07-23
• Study First Submitted QC: 2020-07-25
• Study First Posted: 2020-07-28
• Study Start: 2020-08-26
• Primary Completion: 2021-05-16
• Study Completion: 2021-05-19
• Status Verified: 2022-07
• Results First Submitted: 2022-07-22
• Results First Submitted QC: 2022-11-22
• Last Update Submitted: 2022-11-22
• Results First Posted: 2022-12-19
• Last Update Posted: 2022-12-19

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

1. Hospitalized within the last 36 hours.

2. Receiving any form of supplementary oxygen therapy at baseline.

3. Confirmed COVID-19 viral infection by RTPCR at screening.

4. Age:

   1. 18-65 years old, OR
   2. >65 year-olds can be included after Data Monitoring Committee (DMC) approval

Key

Exclusion Criteria

1. Contraindications/hypersensitivity to P histicola or any of the capsule excipients
2. Patients with chronic hypoxia or underlying significant chronic respiratory disease (such as Chronic Obstructive Pulmonary Disease (COPD), Pulmonary Fibrosis, or Bronchiectasis).
3. Admission to ICU at time of screening.
4. Mechanically ventilated, on continuous positive airway pressure (CPAP), or on non-invasive ventilation at the time of screening.
5. 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.
6. Patient has a diagnosed primary immunodeficiency.
7. Patient has a diagnosis of HIV/AIDS
8. 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)
9. Patient has pre-existing known significant liver disease with Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 5.0 x upper limit of normal (ULN)
10. 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.
11. GI signs or symptoms equivalent to CTCAE v5.0, gastrointestinal disorders, grade 3 or 4 event.
12. 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.
13. Currently participating in an interventional clinical trial (observational studies allowed).
14. Moribund at time of screening

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EDP1815	EDP1815	Patients will receive EDP1815 in addition to standard of care
Placebo	Placebo	Patients will receive placebo in addition to standard of care

Primary Outcome Measures

Name	Time	Method
Change From Baseline to the Lowest S/F Oxygen Ratio in Days 1 to 14	14 days	Worst pulmonary function as measured by the change in Oxygen Saturation (SpO2) / Fraction of Inspired Oxygen (FiO2) \[S/F ratio\]

Secondary Outcome Measures

Name	Time	Method
Intubation and Mechanical-ventilation Free Survival	42 days	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)
Percentage of Participants With Shifts From Each Level of the WHO OSCI Score at Baseline	42 days	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)
Incidence of Clinically Significant Abnormal Lab Parameters	42 days	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
Percentage Change in S/F Ratio	14 days	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.
Overall Survival	42 days	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
Change in S/F Ratio	14 days	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.
Percentage of Participants at Each Level on the WHO OSCI Score	42 days	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)
Number of Participants Remaining at Their Baseline Score on the WHO OSCI (or Lower)	42 days	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)
Percentage of Participants Reporting Each Level of the WHO OSCI Score at Their Worst Post-baseline Day	42 days	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)
The Time in Days Spent at Each Participant's Worst Reported WHO OSCI Score (Excluding Death).	42 days	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).
Number of Days Requiring Oxygen Therapy	42 days	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
Number of Days With Pyrexia	42 days	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
Maximum Daily Temperature	42 days	The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using maximum daily temperature
SpO2 Level	42 days	The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using minimum and maximum SpO2 levels
Time to Discharge	42 days	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.
Time to Oxygen Saturation (SpO2) ≥94%	42 days	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.
Time to Recovery	42 days	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.
Number of Participants Experiencing AEs by Seriousness and Relationship to Treatment	42 days	The safety and tolerability of EDP1815 in participants with COVID-19 will be measured using the number of participants experiencing AEs by seriousness

Trial Locations

Locations (4)

DHR Health Institute; 🇺🇸 Edinburg, Texas, United States

Hacettepe University Adult Hospital; 🇹🇷 Ankara, Turkey

The University Hospital; 🇺🇸 Newark, New Jersey, United States

Robert Wood Johnson University Hospital; 🇺🇸 New Brunswick, New Jersey, United States