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

• ClinicalTrials.gov Identifier: NCT04530136
• Recruitment Status: Completed
• First Posted: August 28, 2020
• Last Update Posted: June 3, 2022
• Sponsor: Pharming Technologies B.V.
• Information provided by (Responsible Party): Pharming Technologies B.V.

Tracking Information

• First Submitted Date: August 26, 2020
• First Posted Date: August 28, 2020
• Last Update Posted Date: June 3, 2022
• Actual Study Start Date: November 30, 2020
• Actual Primary Completion Date: September 7, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 28, 2020)

Disease Severity on the 7-Point WHO Ordinal Scale [ Time Frame: 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 ]

The primary endpoint will be the disease severity on the 7-point WHO Ordinal Scale on day 7. This endpoint has been suggested by WHO for clinical trials in patients with COVID-19

Original Primary Outcome Measures (submitted: August 26, 2020)

Disease Severity on the 7-Point WHO Ordinal Scale [ Time Frame: Assessed on each day after enrollment (worst status) with the use of the WHO Ordinal Scale for Clinical Improvement and the score on day 7 will be analyzed stratified by its baseline value ]

The primary endpoint will be the disease severity on the 7-point WHO Ordinal Scale on day 7. This endpoint has been suggested by WHO for clinical trials in patients with COVID-19

Current Secondary Outcome Measures (submitted: August 26, 2020)

• Clinical improvement [ Time Frame: Daily until day 14 ]
  at least 2 points Ordinal Scale for Clinical Improvement, clinical severity will be assessed.
• Invasive or non-invasive ventilation [ Time Frame: Daily until day 14. ]
  Admission to ICU with invasive or non-invasive ventilation or death will be assessed.
• Acute Lung Injury [ Time Frame: Daily until day 14. ]
  Patients with ALI within 14 days after enrollment, PaO2/FiO2 will be determined daily. This is only relevant for patients with arterial blood gas sampling performed in the ICU or rarely in the medical unit.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Prevention of Severe SARS-CoV-2 Infection in Hospitalized Patients With COVID-19
• Official Title: 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 United States (PROTECT-COVID-19-US)
• Brief Summary: 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.
• 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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Investigator); Primary Purpose: Treatment
• Condition: Confirmed Coronavirus Disease

Intervention

Drug: Ruconest

Patients will be randomized to Ruconest or Standard of Care

Other Name: SOC

Study Arms

• 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.
  Intervention: Drug: Ruconest
• Standard of Care
  SOC
  Intervention: Drug: Ruconest

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 2, 2022): 38
• Original Estimated Enrollment (submitted: August 26, 2020): 120
• Actual Study Completion Date: December 1, 2021
• Actual Primary Completion Date: September 7, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04530136
• Other Study ID Numbers: C1 6201
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Pharming Technologies B.V.
• Original Responsible Party: Same as current
• Current Study Sponsor: Pharming Technologies B.V.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jonathan Bernstein, MD; University of Cincinnati

• PRS Account: Pharming Technologies B.V.
• Verification Date: June 2022