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

NCT ID: NCT04547140

Last Updated: 2023-03-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-29
• Study Completion Date: 2022-01-28

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Liquid Alpha1-Proteinase Inhibitor + Standard Medical Treatment

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.

Group Type: EXPERIMENTAL

Liquid Alpha1-Proteinase Inhibitor (Human)

Intervention Type: BIOLOGICAL

Intravenous infusion 120 mg/kg

Standard Medical Treatment

Intervention Type: DRUG

SMT

Placebo + Standard Medical Treatment

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Intravenous infusion

Standard Medical Treatment

Intervention Type: DRUG

SMT

Interventions

Liquid Alpha1-Proteinase Inhibitor (Human)

Intravenous infusion 120 mg/kg

Intervention Type: BIOLOGICAL

Placebo

Intravenous infusion

Intervention Type: DRUG

Standard Medical Treatment

SMT

Intervention Type: DRUG

Other Intervention Names

Alpha1-proteinase inhibitor; 0.9% Normal Saline

Eligibility Criteria

Inclusion Criteria

1. 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.

2. 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).

3. 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).

4. Participant provides informed consent prior to initiation of any study procedures.

5. 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.

Exclusion Criteria

1. 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]).

2. Clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator, may place the participant at undue medical risk.

3. 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.

4. 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.

5. 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.

6. Known alpha-1 antitrypsin deficiency for which the participant is already receiving alpha1-proteinase inhibitor augmentation therapy.

7. 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.

8. Participants for whom there is limitation of therapeutic effort such as "Do not resuscitate" status.

9. Currently participating in another interventional clinical trial with investigational medical product or device.

10. Participants previously requiring long-term oxygen therapy (home oxygen therapy).

11. History (within the last 2 years) of myocardial infarction, unstable angina, stroke or transient ischemic attacks, pulmonary embolism or deep venous thrombosis.

12. Participant has medical condition (other than COVID-19) that is projected to limit lifespan to ≤ 1 year.

13. Systolic blood pressure < 100 mm Hg or > 160 mm Hg (uncontrolled hypertension) at the time of Screening.

14. Alanine aminotransferase (ALT) ≥ 2 times the upper limit of normal (ULN).

15. Any elevation of total bilirubin at the time of Screening.

16. Estimated glomerular filtration rate (eGFR) < 45 mL/min (or participant is dependent on dialysis/renal replacement therapy) at the time of Screening. eGFR is calculated by the Cockcroft-Gault equation.

17. Hemoglobin < 10 g/dL at the time of Screening.

18. Absolute neutrophil count < 1000/mm^3 at the time of Screening.

19. Platelet count < 75,000/mm^3 at the time of Screening.

20. Participant has history of drug or alcohol abuse within the past 24 months.

21. Participant is unwilling to commit to follow-up visits.

22. Known history of prothrombin gene mutation 20210, homozygous Factor V Leiden mutations, antithrombin III deficiency, protein C deficiency, protein S deficiency or antiphospholipid syndrome.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grifols Therapeutics LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Birmingham VA

Birmingham, Alabama, United States

St. Joseph's Hospital

Phoenix, Arizona, United States

University of Miami Hospital

Miami, Florida, United States

Sparrow Hospital

Lansing, Michigan, United States

Hannibal Clinic

Hannibal, Missouri, United States

Kansas City VA

Kansas City, Missouri, United States

CHI Health Center

Omaha, Nebraska, United States

Columbia University Medical Center

New York, New York, United States

Memphis VA

Memphis, Tennessee, United States

University of Utah

Salt Lake City, Utah, United States

AngioCor Blumenau

Blumenau, Santa Catarina, Brazil

Sociedade Literaria e Caritativa Santo Agostinho

Criciúma, Santa Catarina, Brazil

Universidade Estadual São Paulo - Campus de Botucatu

Botucatu, São Paulo, Brazil

Hospital Dia do Pulmão

Blumenau, , Brazil

Hospital Alemao Oswaldo Cruz

São Paulo, , Brazil

Universidade Federal de Sao Paulo

São Paulo, , Brazil

Hospital Padre Hurtado

Santiago, , Chile

Hospital Carlos Van Buren

Valparaíso, , Chile

Fundación Oftalmológica de Santander

Bucaramanga, Santander Department, Colombia

Unidad Medica para la Salud Integral

San Nicolás de los Garza, , Mexico

Countries

United States; Brazil; Chile; Colombia; Mexico

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GC2006

Identifier Type: -

Identifier Source: org_study_id