Safety and Efficacy of Anti-SARS-CoV-2 Equine Antibody Fragments (INOSARS) for Hospitalized Patients With COVID-19

• ClinicalTrials.gov Identifier: NCT04514302
• Recruitment Status: Not yet recruiting
• First Posted: August 14, 2020
• Last Update Posted: August 14, 2020
• Sponsor: Hospital San Jose Tec de Monterrey
• Information provided by (Responsible Party): José Fernando Castilleja-Leal, Hospital San Jose Tec de Monterrey

Study Description

Brief Summary:

This is a two-center, randomized, placebo-controlled pilot study of anti-SARS-CoV-2 equine immunoglobulin fragments F(ab')2 (INOSARS) to evaluate safety and preliminary efficacy in the treatment of hospitalized COVID-19 patients. Clinical improvement at 28 days from the start of treatment will be evaluated.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Placebo; Drug: Anti-SARS-CoV-2 equine immunoglobulin fragments (INOSARS)	Phase 1; Phase 2

Detailed Description:

This is a two-center, randomized, placebo-controlled pilot study of anti-SARS-CoV-2 equine immunoglobulin fragments F(ab')2 (INOSARS) to evaluate safety and preliminary efficacy in the treatment of hospitalized COVID-19 patients. Subjects included in the study are hospitalized adult patients with a diagnosis of COVID-19, that: 1) require supplementary oxygen or non-invasive mechanical ventilation OR 2) have clinical or imaging evidence of pneumonia OR 3) have laboratory markers of risk of disease progression (high levels of serum inflammatory markers). The sample size is 51 patients randomized to one of three arms: 18 patients to placebo, 16 patients to dose 1 and 17 patients to dose 2 of anti-SARS-CoV-2 equine immunoglobulin F(ab')2 fragments. The safety outcome is the proportion of patients with early and late adverse events until the end of follow-up at 28 days, for both doses of treatment. The primary outcome is the proportion of patients with clinical improvement at 28 days from the start of treatment, comparing between both treatment groups vs placebo. Clinical improvement is defined as a reduction of 1 point in the NIAID 8-point ordinal scale of clinical status for COVID-19 patients or hospital discharge, whichever comes first.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Parallel
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double Blind
• Primary Purpose: Treatment
• Official Title: Pilot Study to Evaluate Safety and Efficacy of Anti-SARS-CoV-2 Equine Immunoglobulin F(ab')2 Fragments (INOSARS) in Hospitalized Patients With COVID-19
• Estimated Study Start Date: October 20, 2020
• Estimated Primary Completion Date: February 20, 2021
• Estimated Study Completion Date: June 20, 2021

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Single dose of 150 mL of saline solution administered intravenously as an infusion at 4.0 mL/min over 40 min. n = 18.	Drug: Placebo; Placebo of saline solution of equal volume and infusion. Content of the infusion bag and tubing will be concealed with opaque covering.; Other Name: Control
Experimental: INOSARS dose 1; Single dose of 2 vials of INOSARS in 150 mL of saline solution administered intravenously as an infusion at 4.0 mL/min over 40 min. n = 16	Drug: Anti-SARS-CoV-2 equine immunoglobulin fragments (INOSARS); INOSARS is a polyvalent passive immunization based on anti-SARS-CoV-2 immunoglobulin F(ab')2 fragments from hyperimmune equine serum. Inactive ingredients: water for injection, sodium chloride and less than 10% of total protein content.; Other Name: INOSARS
Experimental: INOSARS dose 2; Description: Single dose of 6 vials of INOSARS in 150 mL of saline solution administered intravenously as an infusion at 4.0 mL/min over 40 min. n = 17	Drug: Anti-SARS-CoV-2 equine immunoglobulin fragments (INOSARS); INOSARS is a polyvalent passive immunization based on anti-SARS-CoV-2 immunoglobulin F(ab')2 fragments from hyperimmune equine serum. Inactive ingredients: water for injection, sodium chloride and less than 10% of total protein content.; Other Name: INOSARS

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients with improvement in clinical status [ Time Frame: 28 days ]
   The primary endpoint is the proportion of patients with clinical improvement at 28 days after treatment. Clinical improvement is defined as (whichever is first): a) hospital discharge or b) reduction of 1 point in the NIAID 8-point ordinal scale. Scale categories as follows: 1 = not hospitalized; 2 = not hospitalized with limitation of activities and/or oxygen requirement; 3 = hospitalized not requiring supplemental oxygen and not requiring active medical care, 4 = hospitalized requiring active medical care without requiring oxygen supplementation; 5 = hospitalized requiring oxygen supplementation; 6 = hospitalized requiring high-flow oxygen or non-invasive mechanical ventilation; 7 = hospitalized requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8 = death.

Secondary Outcome Measures :

1. Time to clinical improvement [ Time Frame: 28 days ]
   Time from the day of treatment until the first day with clinical improvement, defined as (whichever is first): a) hospital discharge or b) reduction of 1 point in the NIAID 8-point ordinal scale.
2. Proportion of patients that reach a score of 6, 7 or 8 in the NIAID 8-point ordinal scale [ Time Frame: 28 days ]
   Proportion of participant death or non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation requirement.
3. Duration of hospitalization [ Time Frame: 28 days ]
   Measured in days
4. SARS-CoV-2 PCR negativization rate [ Time Frame: 3 days ]
   Proportion of patients that have a negative polymerase chain reaction assay for SARS-CoV-2 at 72 hrs from start of treatment.
5. Proportion of patients with clinical improvement at day 7 [ Time Frame: 7 days ]
   Proportion of patients with clinical improvement at day 7. Clinical improvement is defined as (whichever is first): a) hospital discharge or b) reduction of 1 point in the NIAID 8-point ordinal scale
6. Proportion of patients with immediate adverse events (< 24 hours) [ Time Frame: 24 hours ]
   Proportion of patients that present within 24 hours of treatment with immediate adverse events defined as: skin rash and/or respiratory findings (dyspnea, wheezing, bronchospasm, hypoxia) and/or circulatory compromise (reduction of blood pressure or associated symptoms, i.e. syncope).
7. Proportion of patients with late adverse events (1 - 28 days) [ Time Frame: 28 days ]
   Proportion of patients that present events associated with serum sickness (type 3 hypersensitivity), vasculitis, glomerulonephritis, arthritis.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Subjects of both sexes aged ≥ 18 years
• Patients with a confirmed infection with SARS-CoV-2 by PCR

• Patients admitted for hospitalization for COVID-19 disease that fulfills any of the following:

  1. Clinical or imaging evidence of pneumonia defined as: SpO2 < 94% or PaO2/FiO2 (SpO2/FiO2) < 300 or chest imaging consistent with pneumonia or clinical evidence of pneumonia (fever, cough, dyspnea and respiratory frequency > 24 respirations/min) OR
  2. Score of 4 (hospitalized no oxygen requirement, requires medical care), 5 (hospitalized, low-flow oxygen requirement) or 6 (hospitalized, high-flow oxygen or non-invasive mechanical ventilation requirement) in the NIAID 8-point ordinal scale of clinical status for COVID-19
  3. High risk markers of disease progression (at least on serum inflammatory marker elevated: C reactive protein, D-dimer, lactate dehydrogenase, ferritin)
• Agrees to participate in the study and signs written informed consent (signed by relative if applicable)

Exclusion Criteria:• Patients with known equine allergies

• Patients with past medical history of serum sickness
• Patients with more than 4 days of hospitalization before being randomized in study
• Patients who have received convalescent plasma or intravenous immunoglobulin (IVIG) for COVID-19
• Pregnant or breastfeeding women
• Patients with chronic kidney disease under dialysis
• Patients under invasive mechanical ventilation and/or extracorporeal membrane oxygenation at the beginning of study
• Patients participating in another intervention clinical trial
• Patients who are immunocompromised or with another chronic condition, that is judged by medical staff, to be at higher risk of infection or complications from participating in study
• Patients who are judged by medical staff who are unlikely to survive at 48 hours

Contacts and Locations

Contacts

Contact: Servando Cardona-Huerta, MD, Ph. D.; +5218112121946; servandocardona@tec.mx

Contact: Alejandro Torres-Quintanilla, MD, MSc; +528180205853; atorresq@tec.mx

Locations

Mexico

Hospital San José

Monterrey, Nuevo Leon, Mexico, 64718

Sponsors and Collaborators

Hospital San Jose Tec de Monterrey

Investigators

• Principal Investigator: José F Castilleja-Leal, MD; Wellness and Prevention Center

More Information

Publications:

Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, Hohmann E, Chu HY, Luetkemeyer A, Kline S, Lopez de Castilla D, Finberg RW, Dierberg K, Tapson V, Hsieh L, Patterson TF, Paredes R, Sweeney DA, Short WR, Touloumi G, Lye DC, Ohmagari N, Oh MD, Ruiz-Palacios GM, Benfield T, Fätkenheuer G, Kortepeter MG, Atmar RL, Creech CB, Lundgren J, Babiker AG, Pett S, Neaton JD, Burgess TH, Bonnett T, Green M, Makowski M, Osinusi A, Nayak S, Lane HC; ACTT-1 Study Group Members. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med. 2020 Nov 5;383(19):1813-1826. doi: 10.1056/NEJMoa2007764. Epub 2020 Oct 8.

• Responsible Party: José Fernando Castilleja-Leal, Wellness and Prevention Director, Hospital San Jose Tec de Monterrey
• ClinicalTrials.gov Identifier: NCT04514302
• Other Study ID Numbers: INOSARS-CoV-2 TecSalud
• First Posted: August 14, 2020
• Last Update Posted: August 14, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by José Fernando Castilleja-Leal, Hospital San Jose Tec de Monterrey:

COVID-19; SARS-CoV-2; Immunoglobulin fragments

Additional relevant MeSH terms:

Immunoglobulins; Immunoglobulins, Intravenous; Antibodies; Immunoglobulin Fragments; Immunologic Factors; Physiological Effects of Drugs