Clinical trial NCT04547140: Study to Evaluate the Safety and Efficacy of Liquid Alpha1-Proteinase Inhibitor (Human) in Hospitalized Participants With Coronavirus Disease (COVID-19)
Official title: A Multicenter, Randomized, Double-blind, Placebo-Controlled, Parallel Group Study to Evaluate the Safety and Efficacy of Liquid Alpha1-Proteinase Inhibitor (Human) Plus Standard Medical Treatment (SMT) Versus Placebo Plus SMT in Hospitalized Subjects With COVID-19
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID-19
Keywords: Coronavirus Disease
Severe acute respiratory syndrome coronavirus 2
SARS-CoV-2
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2020-09-14
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Participants Dying or Requiring Intensive Care Unit (ICU) Admission
timeFrame: Up to Day 29
measure: Percentage of Participants Who Are Dependent on High Flow Oxygen Devices or Invasive Mechanical Ventilation
timeFrame: Day 29
Secondary outcomes:
measure: Change From Baseline in National Early Warning Score (NEWS)
timeFrame: Baseline, Days 15 and 29
measure: Time to Clinical Response as Assessed by NEWS Score ≤ 2 Maintained for 24 Hours
timeFrame: Up to Day 29
measure: Time to Hospital Discharge
timeFrame: Up to Day 29
measure: Duration of ICU Stay
timeFrame: Up to Day 29
measure: Duration of Any Oxygen Use
timeFrame: Up to Day 30
measure: Duration of Mechanical Ventilation
timeFrame: Up to Day 29
measure: Mean Change From Baseline in Ordinal Scale
timeFrame: Baseline, Days 15 and 29
measure: Absolute Change From Baseline in Ordinal Scale
timeFrame: Baseline, Days 15 and 29
measure: Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale
timeFrame: Day 15 and Day 29
measure: Time to Sustained Normalization of Temperature
timeFrame: Up to Day 29
measure: Percentage of Participants Who Experienced Sustained Normalization of Fever
timeFrame: Up to Day 29
measure: Number of Participants Who Develop Acute Respiratory Distress Syndrome (ARDS)
timeFrame: Up to Day 29
measure: Time to Clinical Progression
timeFrame: Up to Day 29
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham VA
state: Alabama
city: Phoenix
country: United States
facility: St. Joseph's Hospital
state: Arizona
city: Miami
country: United States
facility: University of Miami Hospital
state: Florida
city: Lansing
country: United States
facility: Sparrow Hospital
state: Michigan
city: Hannibal
country: United States
facility: Hannibal Clinic
state: Missouri
city: Kansas City
country: United States
facility: Kansas City VA
state: Missouri
city: Omaha
country: United States
facility: CHI Health Center
state: Nebraska
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Memphis
country: United States
facility: Memphis VA
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Blumenau
country: Brazil
facility: AngioCor Blumenau
state: Santa Catarina
city: Criciúma
country: Brazil
facility: Sociedade Literaria e Caritativa Santo Agostinho
state: Santa Catarina
city: Botucatu
country: Brazil
facility: Universidade Estadual São Paulo - Campus de Botucatu
state: São Paulo
city: Blumenau
country: Brazil
facility: Hospital Dia do Pulmão
city: São Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz
city: São Paulo
country: Brazil
facility: Universidade Federal de Sao Paulo
city: Santiago
country: Chile
facility: Hospital Padre Hurtado
city: Valparaíso
country: Chile
facility: Hospital Carlos Van Buren
city: Bucaramanga
country: Colombia
facility: Fundación Oftalmológica de Santander
state: Santander
city: San Nicolás de los Garza
country: Mexico
facility: Unidad Medica para la Salud Integral
Study officials:
References: