Study to Evaluate the Safety and Efficacy of Liquid Alpha1-Proteinase Inhibitor (Human) in Hospitalized Participants With Coronavirus Disease (COVID-19)

NCT04547140 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: GC2006
• Study Type: interventional
• Target: 57
• Locations: 5 countries
• Sites: 20

Brief Summary

The purpose of the study is to determine if Liquid Alpha1-Proteinase Inhibitor (Human) (Liquid Alpha1-PI) plus SMT can reduce the proportion of participants dying or requiring intensive care unit (ICU) admission on or before Day 29 or who are dependent on high flow oxygen devices or invasive mechanical ventilation on Day 29 versus placebo plus SMT in hospitalized participants with COVID-19.

Conditions

COVID-19

Keywords

Coronavirus Disease; Severe acute respiratory syndrome coronavirus 2; SARS-CoV-2

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Dying or Requiring Intensive Care Unit (ICU) Admission

  Up to Day 29

• Percentage of Participants Who Are Dependent on High Flow Oxygen Devices or Invasive Mechanical Ventilation

  Day 29

Secondary Outcomes (13)

• Change From Baseline in National Early Warning Score (NEWS)

  Baseline, Days 15 and 29

• Time to Clinical Response as Assessed by NEWS Score ≤ 2 Maintained for 24 Hours

  Up to Day 29

• Time to Hospital Discharge

  Up to Day 29

• Duration of ICU Stay

  Up to Day 29

• Duration of Any Oxygen Use

  Up to Day 30

Study Arms (2)

Liquid Alpha1-Proteinase Inhibitor + Standard Medical Treatment

EXPERIMENTAL

Participants received the first intravenous (IV) infusion of liquid alpha1-proteinase inhibitor (human) 120 milligrams per kilogram (mg/kg), based on body weight on Day 1, followed by second liquid alpha1-proteinase inhibitor (human) dose of 120 mg/kg based on body weight, on Day 8 (second dose was not mandatory and was given at the principal investigator's \[PI\] discretion). Participants also received all standard of care interventions while hospitalized, from Day 1 to Day 29.

Biological: Liquid Alpha1-Proteinase Inhibitor (Human); Drug: Standard Medical Treatment

Placebo + Standard Medical Treatment

PLACEBO COMPARATOR

Participants received IV infusions of 0.9% normal saline of commensurate volume to that of liquid alpha1-proteinase inhibitor as placebo on Day 1 and Day 8 (Day 8 was not mandatory and was given at the PI's discretion). Participants also received all standard of care interventions while hospitalized, from Day 1 to Day 29.

Drug: Placebo; Drug: Standard Medical Treatment

Interventions

Liquid Alpha1-Proteinase Inhibitor (Human) BIOLOGICAL

Intravenous infusion 120 mg/kg

Also known as: Alpha1-proteinase inhibitor

Liquid Alpha1-Proteinase Inhibitor + Standard Medical Treatment

Placebo DRUG

Intravenous infusion

Also known as: 0.9% Normal Saline

Placebo + Standard Medical Treatment

Standard Medical Treatment DRUG

SMT

Liquid Alpha1-Proteinase Inhibitor + Standard Medical Treatment; Placebo + Standard Medical Treatment

Eligibility Criteria

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

You may qualify if:

• Hospitalized male or female participant ≥ 18 years of age at time of screening who is being treated for COVID-19. Participants must be screened within 48 hours (≤ 48 hours) of hospital admission.
• Has laboratory-confirmed novel coronavirus {SARS-CoV-2} infection as determined by qualitative polymerase chain reaction (PCR) (reverse transcriptase \[RT\]-PCR), or other commercial or public health assay approved by regulatory authorities as a diagnostic test for COVID-19 in any specimen during the current hospital admission OR 96 hours prior to the hospital admission date and prior to randomization (the SARS-CoV-2 test results must be performed by a hospital laboratory and the documentation available).
• COVID-19 illness (symptoms) of any duration, including both of the following: a) Radiographic infiltrates by imaging (chest X-Ray, computed tomography (CT) scan, etc.) and/or clinical assessment (evidence of rales/crackles on exam) with peripheral oxygen saturation by pulse oximetry (SpO2) \<94% on room air; b) Any one of the following related to COVID-19: i. Ferritin \> 400 nanogram per milliliter (ng/mL), ii. lactate dehydrogenase (LDH) \> 300 units per liter (U/L), iii. D-Dimers \> reference range, or iv. C-reactive protein (CRP) \> 40 milligram per liter (mg/L).
• Participant provides informed consent prior to initiation of any study procedures.
• Female participants of childbearing potential (and males with female partners of childbearing potential) must agree to use of acceptable contraception methods during study (example, oral, injectable, or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or true abstinence) throughout the study.

You may not qualify if:

• Participants requiring invasive mechanical ventilation or ICU admission or with partial pressure of arterial oxygen/ fraction of inspired oxygen (PaO2/FIO2) ≤ 150 mmHg (i.e., arterial oxygen in millimeter of mercury (mmHg) divided by fraction inspired oxygen concentration \[example, 0.21 for room air\]).
• Clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator, may place the participant at undue medical risk.
• The participant has had a known serious anaphylactic reaction to blood, any blood-derived or plasma product, or known selective immunoglobulin A (IgA) deficiency with anti-IgA antibodies.
• A medical condition in which the infusion of additional fluid is contraindicated (example, decompensated congestive heart failure or renal failure with fluid overload). This includes currently uncontrolled congestive heart failure New York Heart Association Class III or IV stage heart failure.
• Shock that is unresponsive to fluid challenge and/or multiple vasopressors and accompanied by multiorgan failure considered not able to be reversed by the Principal Investigator.
• Known alpha-1 antitrypsin deficiency for which the participant is already receiving alpha1-proteinase inhibitor augmentation therapy.
• Women who are pregnant or breastfeeding. Female participants of child-bearing potential must have a negative test for pregnancy blood or urine human chorionic gonadotropin (HCG)-based assay at screening/baseline visit.
• Participants for whom there is limitation of therapeutic effort such as "Do not resuscitate" status.
• Currently participating in another interventional clinical trial with investigational medical product or device.
• Participants previously requiring long-term oxygen therapy (home oxygen therapy).
• History (within the last 2 years) of myocardial infarction, unstable angina, stroke or transient ischemic attacks, pulmonary embolism or deep venous thrombosis.
• Participant has medical condition (other than COVID-19) that is projected to limit lifespan to ≤ 1 year.
• Systolic blood pressure \< 100 mm Hg or \> 160 mm Hg (uncontrolled hypertension) at the time of Screening.
• Alanine aminotransferase (ALT) ≥ 2 times the upper limit of normal (ULN).
• Any elevation of total bilirubin at the time of Screening.

Sponsors & Collaborators

• Grifols Therapeutics LLC: lead

Study Sites (20)

Birmingham VA

Birmingham, Alabama, 35233, United States

Location

St. Joseph's Hospital

Phoenix, Arizona, 85013, United States

Location

University of Miami Hospital

Miami, Florida, 33125, United States

Location

Sparrow Hospital

Lansing, Michigan, 48912, United States

Location

Hannibal Clinic

Hannibal, Missouri, 63401, United States

Location

Kansas City VA

Kansas City, Missouri, 64128, United States

Location

CHI Health Center

Omaha, Nebraska, 68102, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memphis VA

Memphis, Tennessee, 38104, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

AngioCor Blumenau

Blumenau, Santa Catarina, 89020-430, Brazil

Location

Sociedade Literaria e Caritativa Santo Agostinho

Criciúma, Santa Catarina, 88811-500, Brazil

Location

Universidade Estadual São Paulo - Campus de Botucatu

Botucatu, São Paulo, 18618-686, Brazil

Location

Hospital Dia do Pulmão

Blumenau, 89030-101, Brazil

Location

Hospital Alemao Oswaldo Cruz

São Paulo, 01327-001, Brazil

Location

Universidade Federal de Sao Paulo

São Paulo, 04037-002, Brazil

Location

Hospital Padre Hurtado

Santiago, 8860000, Chile

Location

Hospital Carlos Van Buren

Valparaíso, 2340000, Chile

Location

Fundación Oftalmológica de Santander

Bucaramanga, Santander Department, Colombia

Location

Unidad Medica para la Salud Integral

San Nicolás de los Garza, 66465, Mexico

Location

MeSH Terms

Conditions

COVID-19

Interventions

alpha 1-Antitrypsin; Saline Solution

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Acute-Phase Proteins; Blood Proteins; Proteins; Alpha-Globulins; Serum Globulins; Globulins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

Study was early terminated due to lack of efficacy (futility).

Results Point of Contact

• Title: Rhonda Griffin, Clinical Program Leader/Director
• Organization: Grifols Therapeutics LLC

Rhonda.griffin@grifols.com

+1 919 757 1744

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2020
• First Posted: September 14, 2020
• Study Start: January 29, 2021
• Primary Completion: December 13, 2021
• Study Completion: January 28, 2022
• Last Updated: March 22, 2023
• Results First Posted: March 22, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1); US (10); BR (6); CL (2); CO (1)