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Safety and Effectiveness of an Immunobiological Drug in CoViD-19 (INPB001)

Primary Purpose

COVID-19 Pneumonia, COVID-19 Respiratory Infection, Covid19

Status

Unknown status

Phase

Phase 2

Locations

Argentina

Study Type

Interventional

Intervention

Anti-SARS-CoV-2

Placebo

About this trial

This is an interventional treatment trial for COVID-19 Pneumonia focused on measuring Anti-SARS-CoV-2, Purified F(ab')2 Fragments, Passive immunotherapy, Equine Serum

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects over 18 years old and under 80 years old.
Positive results by RT-PCR for SARS CoV-2
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.
Patient with good disposition towards the study and that signs the informed consent.

Exclusion Criteria:

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%)
Patients with clinical disease corresponding to severe forms (Severe pneumonia: presence of severity criteria (ATS / IDSA), one of two major or three minor criteria.)
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.
Pregnant or lactating women.
Women of childbearing potential not using an effective contraceptive method (withdrawal, intrauterine device, or oral contraceptives).
History of severe anaphylactic reaction with the administration of equine plasma.
Patients with comorbidities that justify a risk of high mortality from causes independent of SARS-CoV-2 infection (eg, stage IV cancer)
Patient who does not consent to participate.

Sites / Locations

Hospital General de Agudos Donación Francisco J. SantojanniRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Anti-SARS-CoV-2

Placebo

Arm Description

Administration of 10 ml of a concentrated equine hyperimmune serum solution with neutralizing activity of SARS-CoV-2 not less than1/5120, administered in slow intravenous infusion (10 ml diluted in100 ml of physiological 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-).

Administration of 10 ml of a control-solution with no-neutralizing activity of SARS-CoV-2, administered in slow intravenous infusion (10ml diluted in 100 ml of physiological solution, administered over 50 to60 minutes in slow drip), produced by ANLIS-Malbrán, administered twice (time 0when incorporated into the study -initial dose- and at 48 hours -second dose-).

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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);

Change in Mortality rate

(b) Change of all-cause mortality at day 28 (OUTCOME - Efficacy);

Change in Mechanical Ventilation Requirement rate

Change in duration of oxygen treatment requirement

(d) Change of the duration of oxygen therapy quantified in days of oxygen therapy (OUTCOME - Efficacy);

Change in Length of Hospitalization

(e) Change of hospital length of hospitalization, quantified in days from study inclusion until hospital discharge (OUTCOME - Efficacy);

Change in frequency of nosocomial infection

(F) Change in the frequency of patients with nosocomial infection (OUTCOME - Efficacy);

Change in Lymphocyte cell count

(g) Change of absolute lymphocyte count (OUTCOME - Efficacy);

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);

Description of adverse events type and frequency

(i) description of reported adverse events, discriminated by their severity, and classified according to MedDRA (OUTCOME - Safety).

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)

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

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).

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).

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).

Full Information

NCT ID

NCT04913779

First Posted

June 1, 2021

Last Updated

September 11, 2021

Sponsor

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

1. Study Identification

Unique Protocol Identification Number

NCT04913779

Brief Title

Safety and Effectiveness of an Immunobiological Drug in CoViD-19

Acronym

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)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Unknown status

Study Start Date

June 1, 2021 (Actual)

Primary Completion Date

November 30, 2021 (Anticipated)

Study Completion Date

December 31, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COVID-19 Pneumonia, COVID-19 Respiratory Infection, Covid19

Keywords

Anti-SARS-CoV-2, Purified F(ab')2 Fragments, Passive immunotherapy, Equine Serum

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Model Description

This is an adaptive phase 2/3, randomized, blinded, placebo-controlled study. 200 total patients (ratio 1:1) will be included with intermediate evaluations when reaching the initial 20 patients (initial analysis of safety and pharmacokinetics), 100 (analysis of safety and efficacy) and 200 (final analysis).

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Allocation

Randomized

Enrollment

200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Anti-SARS-CoV-2

Arm Type

Active Comparator

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Anti-SARS-CoV-2

Other Intervention Name(s)

Purified F(ab')2 Fragments of Equine hyperimmune Serum, F(ab')2 Fragments, Passive Immunotherapy, Equine F(ab')2 Fragments, Hyperimmune Equine Serum, Treatment Group

Intervention Description

Purified F(ab')2 Fragments of Equine hyperimmune Serum with anti-SARS-CoV-2 neutralizing activity (titer 1/5120 or higher)

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Control Group

Intervention Description

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-).

Primary Outcome Measure Information:

Title

Change in time needed to clinical improvement

Description

Time Frame

Reached each day between day 1 and 28 post-inclusion in the study

Secondary Outcome Measure Information:

Title

Change in the number of patients in each World Health Organization (WHO) Ordinal Scale Category (0 to 8 being 0 better and 8 worse)

Description

Time Frame

days 7, 14 and 21 post-inclusion

Title

Change in Mortality rate

Description

(b) Change of all-cause mortality at day 28 (OUTCOME - Efficacy);

Time Frame

28 days post-inclusion

Title

Change in Mechanical Ventilation Requirement rate

Description

Time Frame

28 days post-inclusion

Title

Change in duration of oxygen treatment requirement

Description

(d) Change of the duration of oxygen therapy quantified in days of oxygen therapy (OUTCOME - Efficacy);

Time Frame

28 days post-inclusion

Title

Change in Length of Hospitalization

Description

(e) Change of hospital length of hospitalization, quantified in days from study inclusion until hospital discharge (OUTCOME - Efficacy);

Time Frame

28 days post-inclusion

Title

Change in frequency of nosocomial infection

Description

(F) Change in the frequency of patients with nosocomial infection (OUTCOME - Efficacy);

Time Frame

28 days post-inclusion

Title

Change in Lymphocyte cell count

Description

(g) Change of absolute lymphocyte count (OUTCOME - Efficacy);

Time Frame

28 days post-inclusion

Title

Change in viral RNA Negativization rate on nasopharyngeal swab test

Description

Time Frame

7, 14, 21, and 28 days post-inclusion

Title

Description of adverse events type and frequency

Description

(i) description of reported adverse events, discriminated by their severity, and classified according to MedDRA (OUTCOME - Safety).

Time Frame

28 days post-inclusion

Title

Requirement of additional treatments for Adverse Drug reactions

Description

(j) The number of subjects who required additional treatment as a consequence of reported adverse events in each therapeutic branch (OUTCOME - Safety)

Time Frame

28 days post-inclusion

Title

Describe the AUC of purified F(ab')2 Anti-SARS-CoV-2

Description

(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 Frame

Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days

Title

Describe the Cmax of purified F(ab')2 Anti-SARS-CoV-2

Description

Time Frame

Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days

Title

Describe the t1/2 of purified F(ab')2 Anti-SARS-CoV-2

Description

Time Frame

Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days

Title

Describe the Ke of purified F(ab')2 Anti-SARS-CoV-2

Description

Time Frame

Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects over 18 years old and under 80 years old. Positive results by RT-PCR for SARS CoV-2 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. Patient with good disposition towards the study and that signs the informed consent. Exclusion Criteria: 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%) Patients with clinical disease corresponding to severe forms (Severe pneumonia: presence of severity criteria (ATS / IDSA), one of two major or three minor criteria.) 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. Pregnant or lactating women. Women of childbearing potential not using an effective contraceptive method (withdrawal, intrauterine device, or oral contraceptives). History of severe anaphylactic reaction with the administration of equine plasma. Patients with comorbidities that justify a risk of high mortality from causes independent of SARS-CoV-2 infection (eg, stage IV cancer) Patient who does not consent to participate.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Guillermo A Keller, MD PhD

Phone

011-4961-0943

gkeller@anlis.gob.ar

First Name & Middle Initial & Last Name or Official Title & Degree

Claudio Bonel, PhD

Phone

011-4303-1801

cbonel@anlis.gob.ar

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Guillermo A Keller, PhD

Organizational Affiliation

INPB - ANLIS Malbrán

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hospital General de Agudos Donación Francisco J. Santojanni

City

Ciudad Autónoma De Buenos Aires

ZIP/Postal Code

1408

Country

Argentina

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Guillermo A Keller, MD PhD

Phone

01149610943

gkeller@anlis.gob.ar

First Name & Middle Initial & Last Name & Degree

Claudio Bonel, PhD

Phone

011-4303-2492

cbonel@anlis.gob.ar

First Name & Middle Initial & Last Name & Degree

Guillermo A Keller, MD PhD

First Name & Middle Initial & Last Name & Degree

Guillermo Di Girolamo, MD PhD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Publication of the results of all data obtained is planned.

IPD Sharing Time Frame

After completion of the study.

IPD Sharing Access Criteria

By request to the Principal Investigator

Learn more about this trial

Safety and Effectiveness of an Immunobiological Drug in CoViD-19

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