Evaluating the Impact of EnteraGam In People With COVID-19

NCT04682041 | Completed

• 1 other identifier: PICNIC Study
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), emerged as a potentially life-threatening disease in Wuhan, China, at the end of 2019. Since then, it has spread to almost 200 countries and infection rates are rapidly accelerating. Overactivation of T cells resulting in immune dysfunction, dysfunction of the renin angiotensin system, and antibody-dependent enhancement are thought to contribute to the cytokine storm that results in acute respiratory distress syndrome (ARDS), culminating in death. In addition to causing respiratory symptoms, SARS-CoV-2 can cause diarrhea and has been isolated from the stool. SARS-CoV-2 binds to Angiotensin-converting enzyme 2 (ACE2) on lung alveolar type 2 cells, but ACE2 is also expressed in the absorptive enterocytes from the ileum and colon. The diarrhea may be caused by increased intestinal permeability due to binding of these receptors by the SARS-CoV-2. Thus, an intervention to attenuate this cytokine storm may improve clinical outcomes in people with COVID-19. One such intervention is oral administration of serum bovine immunoglobulins, which decreases interleukin-6 (IL-6) levels safely with minimal side effects. Animal and human clinical studies have shown dietary supplementation with oral immunoglobulins improves mucosal immunity, specifically respiratory/pulmonary and GI mucosa, and decreases systemic inflammation, reducing the symptoms and severity of pulmonary inflammation and viral infections. Hypothesis: Dietary supplementation with EnteraGam® will decrease IL-6 levels and prevent disease progression in SARS-CoV-2 infected individuals. Objectives: To evaluate the effectiveness of the oral nutritional therapy EnteraGam® (serum-derived bovine immunoglobulin/protein isolate) to prevent disease progression of COVID-19 and to decrease IL-6 levels as compared to standard of care in subjects with COVID-19. Methods: Randomized open-label clinical study evaluating the effectiveness of EnteraGam® 10.0 g BID (every 12 hours) added to standard of care, as compared to standard of care alone, in subjects with COVID-19.

Conditions

Covid19

Keywords

SARS-CoV-2; Coronavirus; Bovine Plasma-Derived Immunoglobulin

Outcome Measures

Primary Outcomes (2)

• Change in plasma IL-6 levels

  Variation of IL-6 levels measured in plasma

  From baseline to Week 2

• COVID-19 disease progression by Week 2

  Percentage of patients with COVID-19 who have disease progression by Week 2, defined as: 1. For outpatients, return to emergency department for COVID-19 related manifestations or worsening of ≥1 level on the World Health Organization (WHO) 9-point ordinal scale. 2. For inpatients, worsening of ≥1 level on the WHO 9-point ordinal scale.

  From baseline to Week 2

Secondary Outcomes (13)

• Change in dyspnea

  At Week 2

• Change in diarrhea

  At Week 2

• Change in fever

  At Week 2

• Change in neutrophil count

  At Week 2

• Change in lymphocyte count

  At Week 2

Other Outcomes (1)

• Incidence of Adverse Events

  From baseline to Week 2

Study Arms (2)

EnteraGam + standard of care

EXPERIMENTAL

Subjects will receive EnteraGam® (oral nutritional therapy) + standard of care for COVID-19 for 2 weeks. Total study duration (including the screening phase) will be approximately 4 weeks.

Dietary Supplement: Bovine Plasma-Derived Immunoglobulin Concentrate; Other: Standard of care

Control (standard of care)

OTHER

Subjects will receive standard of care for COVID-19 alone for 2 weeks. Total study duration (including the screening phase) will be approximately 4 weeks.

Other: Standard of care

Interventions

Bovine Plasma-Derived Immunoglobulin Concentrate DIETARY_SUPPLEMENT

EnteraGam® 10.0 g, containing 5.0 g of serum-derived bovine immunoglobulin/protein isolate (SBI) BID (every 12 hours) for 2 weeks.

Also known as: EnteraGam®

EnteraGam + standard of care

Standard of care OTHER

Standard of care PSMAR protocol for COVID-19 patients.

Control (standard of care); EnteraGam + standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is ≥18 years of age.
• Male or female. Females of childbearing (reproductive) potential must have a negative urine pregnancy test at screening.
• Subject with diagnosis of COVID-19 based on + RNA or immunoglobulin M (IgM) test or compatible clinical presentation\* who:
• is being discharged from the emergency department without hospitalization, or
• (\*)Compatible clinical presentation will consider compatible symptoms (cough, fever, myalgia, dyspnea, ageusia / anosmia) and examination of general condition, heart rate and respiratory rate, oxygen saturation, cardiopulmonary auscultation, compatible radiology.
• Ability to consume EnteraGam.
• Subject or surrogate decision maker is capable of understanding the requirements of the study, understands the language of the informed consent form, and is capable and willing to sign the informed consent form.

You may not qualify if:

• Female subjects who are pregnant or breast-feeding.
• Subject is enrolled in another randomized clinical trial.
• Subject is taking anti-IL-6 treatment (e.g. tocilizumab), anti-IL-1 treatment (e.g. canakinumab, anakinra), or other biologic immunomodulators or immunosuppressant drugs. Note: Topical/inhaled immunomodulators and corticosteroids are not restricted.
• Subject has immediate need for GI surgery or intervention for active GI bleeding, pancreatitis, peritonitis, intestinal obstruction, or intra-abdominal abscess.
• Subject has active inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease, or celiac disease), GI malignancy, GI obstruction, pancreatitis, gastroparesis, carcinoid syndrome, amyloidosis, ileus, or cholelithiasis.
• Subject has active gastric ulcer, duodenal ulcer, diverticulitis, colitis, enteritis, infectious gastroenteritis, or GI neoplasm, other than benign polyps.
• Subject has a history of allergy or intolerance to beef or to any ingredient in the product.
• Subject has active drug or alcohol abuse that in the opinion of the investigator may interfere with the subject's ability to comply with this protocol.
• History of uncontrolled psychiatric disorders (includes significant depression or suicidal ideation), that in the opinion of the investigator may interfere with the subject's ability to comply with this protocol.
• In the opinion of the investigator, progression to death is imminent and highly likely within the next 24 hours.

Sponsors & Collaborators

• Entera Health, Inc: lead
• Lemus Buhils, SL: collaborator
• Clinical Research Unit, IMIM (Hospital del Mar Medical Research Institute): collaborator

Study Sites (1)

Hospital del Mar

Barcelona, 08003, Spain

Location

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Roberto Güerri Fernández, MD, PhD

  Hospital del Mar (Barcelona, Spain)

  PRINCIPAL INVESTIGATOR

• Netanya S. Utay, MD

  University of Texas Health Science Center at Houston (Houston, TX, USA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized open-label clinical study evaluating the effectiveness of EnteraGam 10.0 g BID added to standard of care, as compared to standard of care alone, in subjects with COVID-19. Eligible subjects will be randomized in a 2:1 ratio.

Study Record Dates

• First Submitted: December 18, 2020
• First Posted: December 23, 2020
• Study Start: December 22, 2020
• Primary Completion: December 20, 2021
• Study Completion: February 21, 2022
• Last Updated: April 20, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)