Prevention of Severe SARS-CoV-2 Infection in Hospitalized Patients With COVID-19

Recombinant Human C1 Esterase Inhibitor (Ruconest®) in the Prevention of Severe SARS-CoV-2 Infection in Hospitalized Patients With COVID-19: a Randomized, Parallel-group, Open-label, Multi-center Pilot Trial in the US

The primary purpose of this study is to evaluate if adding rhC1-INH to standard of care (SOC) in patients admitted for stage II COVID-19 infection may reduce the risk of disease progression, i.e. ALI requiring mechanical ventilation, or increase the chance of a faster clinical improvement compared to SOC alone.

Study Overview

• Status: Completed
• Conditions: Confirmed Coronavirus Disease
• Intervention / Treatment: Drug: Ruconest

Detailed Description

Patients fulfilling all eligibility criteria will be randomized in a 2:1 ratio in an open-label controlled design to treatment with rhC1-INH in addition to SOC or SOC only starting on day 0. The first rhC1-INH treatment will be administered on the same day and continued for a total of 4 days.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Virtua Marlton Hospital
    • Mount Holly, New Jersey, United States, 08060
      • Virtua Memorial Hospital
    • Ridgewood, New Jersey, United States, 07450
      • The Valley Hospital
    • Voorhees, New Jersey, United States, 08043
      • Virtua Voorhees Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-85 years,
• Admitted to the hospital because of confirmed positive SARS-CoV-2 (COVID-19 infection).
• Evidence of pulmonary involvement on CT scan or X-Ray of the chest,
• Symptom onset within the previous 10 days AND at least one additional risk factor for progression to mechanical ventilation: 1) arterial hypertension, 2) >50 years, 3) obesity (BMI>30.0 kg/m2), 4) history of cardiovascular disease, 5) chronic pulmonary disease, 7) chronic renal disease, 6) C-reactive protein of >35mg/L, 7) oxygen saturation at rest in ambient air of <94%

Exclusion Criteria:

• Contraindications to the class of drugs under study (C1 esterase inhibitor);
• History or suspicion of allergy to rabbits;
• Women who are of childbearing potential and not using methods of contraception during the entire study period;
• Pregnant or breastfeeding females or has a positive serum β-human chorionic gonadotropin (hCG) pregnancy test at screening;
• Chronic liver disease (any Child-Pugh score B or C);
• Currently admitted to an ICU or expected admission within the next 24 hours; and
• Currently receiving invasive or non-invasive ventilation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ruconest; Patients receive (150 U/ml) of Ruconest at a 50 U/kg dose (max dose of 4200 U) as a slow intravenous injection via a peripheral every 12 hours; for 4 days. A total of 8 doses will be administered.	Drug: Ruconest; Patients will be randomized to Ruconest or Standard of Care; Other Names: SOC
Other: Standard of Care; SOC	Drug: Ruconest; Patients will be randomized to Ruconest or Standard of Care; Other Names: SOC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Each Score on WHO 7-point Outcome Scale at Day 7	The disease severity on the 7-point WHO Ordinal Scale on Day 7 was the primary objective of this study. This endpoint had been suggested by the WHO for clinical trials in patients with Covid-19. The ordinal scale measures illness severity over time. The higher score, the worst outcome: meaning score 1, no limitation in activities and score 7, death.	Assessed on each day after enrollment (worst status) with the use of the WHO Ordinal Scale and the score on day 7 will be analyzed stratified by its baseline value

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Clinical Improvement	Time from randomization to an improvement of (at least) two (score) points on the seven-category WHO Ordinal Scale or live discharge from hospital whichever came first within 14 days after enrollment	Daily until day 14
Invasive (Mechanical) or Non-invasive Ventilation	Admission to ICU with invasive or non-invasive ventilation will be assessed.	Daily until day 14.
Number of Days Hospitalized	Amount of days the patient is hospitalized during participation in the study.	between D0 and D90

Collaborators and Investigators

• Sponsor: Pharming Technologies B.V.
• Investigators: Principal Investigator: Jonathan Bernstein, MD, University of Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2020
• Primary Completion (Actual): September 7, 2021
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: August 26, 2020
• First Submitted That Met QC Criteria: August 26, 2020
• First Posted (Actual): August 28, 2020

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Complement C1 Inhibitor Protein
• Other Study ID Numbers: C1 6201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No