Efficacy and Safety Study of IV Ravulizumab in Patients With COVID-19 Severe Pneumonia

Phase 3

Terminated

• Conditions: Acute Lung Injury; Pneumonia, Viral; COVID-19 Severe Pneumonia; Acute Respiratory Distress Syndrome
• Interventions: Biological: Ravulizumab; Other: BSC

• Registration Number: NCT04369469
• Lead Sponsor: Alexion Pharmaceuticals, Inc.

Brief Summary

This study evaluated the efficacy, safety, pharmacokinetics, and pharmacodynamics of ravulizumab administered in adult participants with coronavirus disease 2019 (COVID-19) severe pneumonia, acute lung injury, or acute respiratory distress syndrome. Participants were randomly assigned to receive ravulizumab in addition to best supportive care (BSC) (2/3 of the participants) or BSC alone (1/3 of the participants). BSC consisted of medical treatment and/or medical interventions per routine hospital practice.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-04-28
• Study First Submitted QC: 2020-04-28
• Study First Posted: 2020-04-30
• Study Start: 2020-05-10
• Primary Completion: 2021-02-08
• Study Completion: 2021-04-08
• Results First Submitted: 2022-02-15
• Status Verified: 2022-05
• Results First Submitted QC: 2022-05-04
• Last Update Submitted: 2022-05-04
• Results First Posted: 2022-05-24
• Last Update Posted: 2022-05-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 202

Inclusion Criteria

1. Males or female participants ≥ 18 years of age and ≥ 40 kilograms at the time of providing informed consent.
2. Confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 infection (for example, via polymerase chain reaction and/or antibody test) presenting as severe COVID-19 requiring hospitalization.
3. Severe pneumonia, acute lung injury, or acute respiratory distress syndrome confirmed by computed tomography or X-ray at Screening or within the 3 days prior to Screening, as part of the participant's routine clinical care.
4. Respiratory distress requiring mechanical ventilation, which can be either invasive (requiring endotracheal intubation) or noninvasive (with continuous positive airway pressure or bilevel positive airway pressure).
5. Female participants of childbearing potential and male participants with female partners of childbearing potential must follow protocol specified contraception guidance for avoiding pregnancy for 8 months after treatment with the study drug.

Exclusion Criteria

1. Participant was not expected to survive for more than 24 hours.

2. Participant was on invasive mechanical ventilation with intubation for more than 48 hours prior to Screening.

3. Severe pre-existing cardiac disease (that is, New York Heart Association Class 3 or Class 4, acute coronary syndrome or persistent ventricular tachyarrhythmias).

4. Participant had an unresolved Neisseria meningitidis infection.

5. Used the following medications and therapies:

   • Current treatment with a complement inhibitor or
   • Intravenous immunoglobulin within 4 weeks prior to randomization on Day 1

6. Treatment with investigational therapy in a clinical study within 30 days before randomization, or within 5 half-lives of that investigational therapy, whichever was greater. Exceptions:

   • Investigational therapies were allowed if received as part of BSC through an expanded access protocol or emergency approval for the treatment of COVID-19.
   • Investigational antiviral therapies (such as remdesivir) were allowed even if received as part of a clinical study.

7. Female participants who were breastfeeding or who have a positive pregnancy test result at Screening.

8. History of hypersensitivity to any ingredient contained in the study drug, including hypersensitivity to murine proteins.

9. Participant who was not currently vaccinated against Neisseria meningitidis, unless the participant agrees to receive prophylactic treatment with appropriate antibiotics for at least 8 months after the last infusion of study drug or until at least 2 weeks after the participant receives vaccination against Neisseria meningitidis.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1 - Ravulizumab + BSC	Ravulizumab	-
Group 1 - Ravulizumab + BSC	BSC	-
Group 2 - BSC alone	BSC	-

Primary Outcome Measures

Name	Time	Method
Survival (Based On All-Cause Mortality) in Participants in the ITT Population At Day 29	Day 29	Survival (based on all-cause mortality) in Participants in the ITT Population at Day 29 was analyzed. The result for the survival was estimated survival combined over all imputations.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline In Sequential Organ Failure Assessment (SOFA) At Day 29	Baseline, Day 29	Baseline was defined as the last available assessment on or before Day 1 for all participants. Participants were evaluated using the SOFA score, an assessment tool that included a review of 6 organ systems: respiratory, renal, hepatic, cardiac, coagulation, and central nervous system. Each organ system was scored from 0 to 4 points using the worst value observed within the previous 24 hours. The total score ranged from 0 to 24, with a higher score indicating a worse condition.
Serum Ravulizumab Concentrations Prior to Dosing on Day 1 and Day 29	Day 1 and Day 29	Results are reported in micrograms/milliliter (μg/mL).
Change From Baseline In Terminal Complement Complex C5b-9 At Day 29	Baseline, Day 29
Change From Baseline In Serum Free Complement Component 5 Concentrations At Day 29	Baseline, Day 29
Number Of Days Free Of Mechanical Ventilation At Day 29	Day 29	The number of days free of mechanical ventilation was defined as the total number of days from Day 1 to Day 29 without invasive or non-invasive mechanical ventilation.
Change From Baseline In Peripheral Capillary Oxygen Saturation/Fraction Of Inspired Oxygen (SpO2/FiO2) At Day 29	Baseline, Day 29	Oxygenation was measured using the SpO2 and the amount of supplemental oxygen as measured by the FiO2 received by taking the ratio of these 2 measures at the same time point.
Number of Days the Participants Were Alive and Not in the Hospital	Day 1 through Day 29	The number of days that the participants were alive and not in the hospital from Day 1 through Day 29 are presented.
Estimated Number of Participants Alive At Up To Day 60 and At Up To Day 90	Up to Day 60 and Up to Day 90	For this analysis, 2 participants in Group 1 (Ravulizumab + BSC) and 1 participant in Group 2 (BSC Alone) were censored at Day 90. The estimated number of participants alive for this analysis was calculated using the method of Kaplan and Meier (KM) and compared using a log-rank test stratified by intubated or not intubated on Day 1 as a sensitivity analysis. This Outcome Measure was designed to project an estimate of how many participants would be alive and not the actual number of alive participants. All-Cause Mortality data is provided in the Adverse Events Section.
Number of Days the Participants Were Alive and Not in ICU	Day 1 through Day 29	The number of days that the participants were alive and not in the ICU from Day 1 through Day 29 are presented.

Trial Locations

Locations (38)

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Central Arkansas Veterans Healthcare System; 🇺🇸 Little Rock, Arkansas, United States

Norton Healthcare; 🇺🇸 Louisville, Kentucky, United States

UC Irvine Medical Center; 🇺🇸 Orange, California, United States

MedStar Georgetown University Hospital; 🇺🇸 Washington, District of Columbia, United States

Boston Medical Center; 🇺🇸 Boston, Massachusetts, United States

LAC/USC Health Center; 🇺🇸 Los Angeles, California, United States

NYU Langone Health Center; 🇺🇸 New York, New York, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Hôpital Raymond Poincaré; 🇫🇷 Garches, Hauts De Seine, France

Medical Hospital, Tokyo Medical and Dental University; 🇯🇵 Bunkyō-Ku, Tokyo-To, Japan

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

Westchester Medical Center; 🇺🇸 Valhalla, New York, United States

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States

Hôpital Henri Mondor; 🇫🇷 Créteil, Val De Marne, France

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Spain

St James's University Hospital; 🇬🇧 Leeds, West Yorkshire, United Kingdom

Hammersmith Hospital; 🇬🇧 London, Greater London, United Kingdom

King's College Hospital; 🇬🇧 London, Greater London, United Kingdom

Hospital Universitario Ramon y Cajal; 🇪🇸 Madrid, Spain

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Queen Elizabeth Hospital; 🇬🇧 Birmingham, West Midlands, United Kingdom

Baptist Memorial Hospital; 🇺🇸 Memphis, Tennessee, United States

Mayo Clinic Health System in Eau Claire; 🇺🇸 Eau Claire, Wisconsin, United States

Hôpital Bicêtre; 🇫🇷 Le Kremlin-Bicêtre cedex, Val De Marne, France

Jikei University Hospital; 🇯🇵 Minato-Ku, Tokyo, Japan

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Hospital Universitari de Bellvitge; 🇪🇸 L'Hospitalet De Llobregat, Barcelona, Spain

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Mayo Clinic Health System; 🇺🇸 La Crosse, Wisconsin, United States

Tokyo Medical University Hospital; 🇯🇵 Shinjuku-Ku, Tokyo, Japan

Baltimore VA Medical Center; 🇺🇸 Baltimore, Maryland, United States

Mayo Clinic Florida; 🇺🇸 Jacksonville, Florida, United States

University of Florida; 🇺🇸 Jacksonville, Florida, United States

Royal Liverpool University Hospital; 🇬🇧 Liverpool, Merseyside, United Kingdom