Evaluating the Impact of EnteraGam In People With COVID-19

Subject population:

Outpatient and inpatient male and non-pregnant females ≥18 years old, diagnosed with COVID-19 in the emergency department or admitted to the hospital but not requiring invasive mechanical ventilation or in the ICU.

Approximately 420 subjects will be randomized (2:1 ratio), 280 in the EnteraGam® arm and 140 in the control (standard of care) arm.

Nutritional intervention:

ImmunoLin is the active ingredient in EnteraGam®, a medical food developed and marketed by Entera Health in the US since 2013. ImmunoLin is an edible bovine plasma-derived immunoglobulin concentrate developed in 2001 as an immunoglobulin enriched plasma preparation for the human dietary supplement market. ImmunoLin is Generally Regarded as Safe (GRAS) following a letter of no objection from the US FDA in 2008. Physicians have prescribed EnteraGam® for patients with a variety of GI-related conditions.

Statistical methodology:

Efficacy: Based on per protocol analysis. Subjects lacking an assessment at Week 2 will be included in the analysis using the last available post-baseline data. Three pre-specified secondary analyses will be performed: 1) restricted to subjects with a comorbidity considered a major risk factor for hospitalization and disease severity (diabetes, cardiovascular disease, chronic lung disease, chronic renal disease, immunocompromised state); 2) restricted to age ≥ 50 years; 3) by inpatient only and outpatient only subgroups.

Additional analysis of covariance models with adjustment for Baseline characteristics and interactions may be examined in supportive or exploratory analyses.

Safety: All safety analyses will be based on all subjects who are randomized to EnteraGam and subsequently receive at least 1 packet of investigational product. Safety assessments will be analyzed by frequency of events/abnormalities for categorical values or summarized using descriptive statistics (mean, standard deviation, median, range, and number of observations).

Inclusion criteria

• 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
• is admitted to the hospital or was previously hospitalized and still in the hospital, does not require invasive mechanical ventilation and does not require management in the intensive care unit. Inpatients can be enrolled in the study at any time of their hospitalization, if they comply with the inclusion criteria.

(*)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.

Exclusion criteria

• 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.