Safety and Effectiveness of an Immunobiological Drug in CoViD-19

Covid19 Clinical Trial

— INPB001  

Official title:

Study to Evaluate the Safety and Effectiveness of an Immunobiological Drug (Anti SARS-CoV-2) in the Treatment of Coronavirus Disease 2019 (CoViD-19)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04913779
• Other study ID #: INPB001
• Secondary ID: PRIISA.BA 2578RE
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: June 1, 2021
• Est. completion date: December 31, 2021

Study information

• Verified date: September 2021
• Source: Administracion Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbran
• Contact: Guillermo A Keller, MD PhD
• Phone: 011-4961-0943
• Email: gkeller[@]anlis.gob.ar
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aims of this study is to analyze the efficacy and safety of a passive immunotherapy strategy using hyperimmune equine serum known as Anti-SARS-CoV-2 elaborated by the National Institute for the Production of Biologicals (ANLIS-Malbrán) as an addition to the standard therapeutic approach for hospitalized patients with COVID-19, in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection aged 18 to 80 years.

Description:

This is an adaptive phase II/III study that aims to analyze the efficacy and safety of a immunobiological drug (Anti SARS-CoV-2) in the treatment of CoViD-19. This treatment is a passive immunotherapy strategy developed as a purified F(ab')2 fraction of equine hyperimmune serum (Anti-SARS-CoV-2). The equine serum was generated from antigenic stimulation with the SARS-CoV-2 receptor binding domain (RBD) purified protein.

This type of product (equine hyperimmune serum F(ab')2) has been widely used in our country in the last 100 years with satisfactory results and an acceptable safety profile in the treatment of accidents with poisonous animals such as anti-loxosceles, anti -latrodectus, anti-scorpionic, and anti-phoneutria, anti-bothropic, anti-micrurus, and anti-crotalic sera, all developed by the National Institute of Biological Production (ANLIS-Malbrán) and distributed free of charge in public hospitals in the country .

In the present study, evaluates the effect and safety of this immunobiological treatment in patients with COVID-19 that require hospitalization.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2021
• Est. primary completion date: November 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Subjects over 18 years old and under 80 years old.

2. Positive results by RT-PCR for SARS CoV-2

3. Clinical picture compatible with respiratory compromise in the form of pneumonia attributed to COVID-19 (Stage 3, 4 or 5 according to the WHO scale), lasting up to 72 hours from the onset of symptoms to their evaluation to be incorporated into the study.

4. Patient with good disposition towards the study and that signs the informed consent.

Exclusion Criteria:

1. Patients with clinical disease corresponding to mild / asymptomatic forms (Absence of radiological infiltrate and risk factors, with normal auscultation and arterial saturation of oxygen (SatO2) greater than 95%)

2. Patients with clinical disease corresponding to severe forms (Severe pneumonia:

presence of severity criteria (ATS / IDSA), one of two major or three minor criteria.)

3. Patients who have received other therapeutic strategies in the framework of an experimental study that make it difficult to evaluate the results obtained, including (but not limited to): convalescent plasma, lopinavir / ritonavir, hydroxychloroquine, and azithromycin.

4. Pregnant or lactating women.

5. Women of childbearing potential not using an effective contraceptive method (withdrawal, intrauterine device, or oral contraceptives).

6. History of severe anaphylactic reaction with the administration of equine plasma.

7. Patients with comorbidities that justify a risk of high mortality from causes independent of SARS-CoV-2 infection (eg, stage IV cancer)

8. Patient who does not consent to participate.

Related Conditions & MeSH terms

• COVID-19
• COVID-19 Pneumonia
• Covid19
• Respiratory Tract Infections

Intervention

Drug:
• Anti-SARS-CoV-2
Purified F(ab')2 Fragments of Equine hyperimmune Serum with anti-SARS-CoV-2 neutralizing activity (titer 1/5120 or higher)
• Placebo
Administration of 10 ml of a control-solution without neutralizing activity against SARS-CoV-2, administered in slow intravenous infusion (10 ml diluted in 100 ml of saline solution, administered over 50 to 60 minutes in slow drip), produced by ANLIS-Malbrán, administered twice (time 0 when incorporated into the study -initial dose- and at 48 hours -second dose-).

Locations

Country	Name	City	State
Argentina	Hospital General de Agudos Donación Francisco J. Santojanni	Ciudad Autónoma De Buenos Aires

Sponsors (1)

Lead Sponsor	Collaborator
Administracion Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbran

Country where clinical trial is conducted

Argentina, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in time needed to clinical improvement	In subjects admitted to the general ward for active infection by SARS-CoV-2 and a clinical picture of pneumonia who receive supportive treatment recommended by the guidelines of the Ministry of Health of the Argentine Nation (Population), if slow intravenous administration of Anti SARS-CoV-2 in two doses 48 hours apart (Intervention) added to supportive treatment, compared to supportive treatment alone (patients will receive slow intravenous administration of a placebo solution in two doses 48 hours apart to maintain the "blind" as Comparator), changes the time needed to clinical improvement (Outcome), during 28 days after the assignment (Time).	Reached each day between day 1 and 28 post-inclusion in the study
Secondary	Change in the number of patients in each World Health Organization (WHO) Ordinal Scale Category (0 to 8 being 0 better and 8 worse)	(a) Change in the number of patients in each World Health Organization Ordinal Scale Category (0 to 8 being 0 better and 8 worse), expecting a lower proportion of patients in categories 4, 5, 6, and 7 (OUTCOME - Efficacy);	days 7, 14 and 21 post-inclusion
Secondary	Change in Mortality rate	(b) Change of all-cause mortality at day 28 (OUTCOME - Efficacy);	28 days post-inclusion
Secondary	Change in Mechanical Ventilation Requirement rate	(c) Determination of the frequency of invasive mechanical ventilation in the total analysis period (OUTCOME - Efficacy);	28 days post-inclusion
Secondary	Change in duration of oxygen treatment requirement	(d) Change of the duration of oxygen therapy quantified in days of oxygen therapy (OUTCOME - Efficacy);	28 days post-inclusion
Secondary	Change in Length of Hospitalization	(e) Change of hospital length of hospitalization, quantified in days from study inclusion until hospital discharge (OUTCOME - Efficacy);	28 days post-inclusion
Secondary	Change in frequency of nosocomial infection	(F) Change in the frequency of patients with nosocomial infection (OUTCOME - Efficacy);	28 days post-inclusion
Secondary	Change in Lymphocyte cell count	(g) Change of absolute lymphocyte count (OUTCOME - Efficacy);	28 days post-inclusion
Secondary	Change in viral RNA Negativization rate on nasopharyngeal swab test	(h) change in the proportion of patients with detected viral RNA and the viral RNA load, measured by quantitative reverse transcriptase polymerase chain reaction (RT-PCR), on day 7, 14, 21, and 28 (OUTCOME - Efficacy);	7, 14, 21, and 28 days post-inclusion
Secondary	Description of adverse events type and frequency	(i) description of reported adverse events, discriminated by their severity, and classified according to MedDRA (OUTCOME - Safety).	28 days post-inclusion
Secondary	Requirement of additional treatments for Adverse Drug reactions	(j) The number of subjects who required additional treatment as a consequence of reported adverse events in each therapeutic branch (OUTCOME - Safety)	28 days post-inclusion
Secondary	Describe the AUC of purified F(ab')2 Anti-SARS-CoV-2	(k1) Describe area under the curve (AUC) of the active drug, based on concentrations determined in plasma samples obtained from the first 20 patients	Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days
Secondary	Describe the Cmax of purified F(ab')2 Anti-SARS-CoV-2	(k2) Describe maximum plasma concentration (Cmax) of the active drug, based on concentrations determined in plasma samples obtained from the first 20 patients (at time Minute 0 min, hours 1, 3, 6, 24, 48, 49 and 96, day 7, 14, 21 and 28 days).	Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days
Secondary	Describe the t1/2 of purified F(ab')2 Anti-SARS-CoV-2	(k3) Describe plasma half life (t1/2) of the active drug, based on concentrations determined in plasma samples obtained from the first 20 patients (at time Minute 0 min, hours 1, 3, 6, 24, 48, 49 and 96, day 7, 14, 21 and 28 days).	Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days
Secondary	Describe the Ke of purified F(ab')2 Anti-SARS-CoV-2	(k4) Describe elimination constant (Ke) of the active drug, based on concentrations determined in plasma samples obtained from the first 20 patients (at time Minute 0 min, hours 1, 3, 6, 24, 48, 49 and 96, day 7, 14, 21 and 28 days).	Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days