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.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Confirmed Coronavirus Disease	Drug: Ruconest	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: November 30, 2020
• Actual Primary Completion Date: September 7, 2021
• Actual Study Completion Date: December 1, 2021

Arms and Interventions

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 Name: SOC
Standard of Care; SOC	Drug: Ruconest; Patients will be randomized to Ruconest or Standard of Care; Other Name: SOC

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. Clinical improvement [ Time Frame: Daily until day 14 ]
   at least 2 points Ordinal Scale for Clinical Improvement, clinical severity will be assessed.
2. 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.
3. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, New Jersey

The Valley Hospital

Ridgewood, New Jersey, United States, 07450

Sponsors and Collaborators

Pharming Technologies B.V.

Investigators

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

More Information

• Responsible Party: Pharming Technologies B.V.
• ClinicalTrials.gov Identifier: NCT04530136
• Other Study ID Numbers: C1 6201
• First Posted: August 28, 2020
• Last Update Posted: June 3, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

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

Additional relevant MeSH terms:

COVID-19; Complement C1 Inhibitor Protein; Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Complement Inactivating Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs