Trial Outcomes & Findings for Prevention of Severe SARS-CoV-2 Infection in Hospitalized Patients With COVID-19 (NCT NCT04530136)

Last Updated: 2024-02-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

38 participants

Primary outcome timeframe

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

Results posted on

2024-02-16

Participant Flow

Participants were randomized to two parallel groups in a 2:1 ratio to receive either rhC1INH (intervention) in addition to standard of care (SOC) or SOC treatment (control). Randomization was stratified by the study site before inclusion using randomly permuted block sizes of four.

Participant milestones

Participant milestones
Measure	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. Ruconest: Patients will be randomized to Ruconest or Standard of Care	Standard of Care SOC Ruconest: Patients will be randomized to Ruconest or Standard of Care
Overall Study STARTED	27	11
Overall Study COMPLETED	24	7
Overall Study NOT COMPLETED	3	4

Reasons for withdrawal

Reasons for withdrawal
Measure	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. Ruconest: Patients will be randomized to Ruconest or Standard of Care	Standard of Care SOC Ruconest: Patients will be randomized to Ruconest or Standard of Care
Overall Study Lost to Follow-up	2	3
Overall Study Withdrawal by Subject	1	0
Overall Study Death	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ruconest n=27 Participants 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. Ruconest: Patients will be randomized to Ruconest or Standard of Care	Standard of Care n=11 Participants SOC Ruconest: Patients will be randomized to Ruconest or Standard of Care	Total n=38 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	23 Participants n=99 Participants	7 Participants n=107 Participants	30 Participants n=206 Participants
Age, Categorical >=65 years	4 Participants n=99 Participants	4 Participants n=107 Participants	8 Participants n=206 Participants
Age, Continuous	55.93 years STANDARD_DEVIATION 11.84 • n=99 Participants	55.18 years STANDARD_DEVIATION 8.99 • n=107 Participants	55.55 years STANDARD_DEVIATION 10.42 • n=206 Participants
Sex: Female, Male Female	13 Participants n=99 Participants	3 Participants n=107 Participants	16 Participants n=206 Participants
Sex: Female, Male Male	14 Participants n=99 Participants	8 Participants n=107 Participants	22 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) White	25 Participants n=99 Participants	8 Participants n=107 Participants	33 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants	2 Participants n=107 Participants	3 Participants n=206 Participants
Body Mass Index	34.58 kg/m^2 STANDARD_DEVIATION 6.07 • n=99 Participants	30.54 kg/m^2 STANDARD_DEVIATION 8.55 • n=107 Participants	32.56 kg/m^2 STANDARD_DEVIATION 7.31 • n=206 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Ruconest n=27 Participants 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. Ruconest: Patients will be randomized to Ruconest or Standard of Care	Standard of Care n=11 Participants SOC Ruconest: Patients will be randomized to Ruconest or Standard of Care
Number of Participants With Each Score on WHO 7-point Outcome Scale at Day 7 WHO ordinal scale 1	6 Participants	0 Participants
Number of Participants With Each Score on WHO 7-point Outcome Scale at Day 7 WHO ordinal scale 2	20 Participants	8 Participants
Number of Participants With Each Score on WHO 7-point Outcome Scale at Day 7 WHO ordinal scale 3	0 Participants	0 Participants
Number of Participants With Each Score on WHO 7-point Outcome Scale at Day 7 WHO ordinal scale 4	1 Participants	0 Participants
Number of Participants With Each Score on WHO 7-point Outcome Scale at Day 7 WHO ordinal scale 5	0 Participants	1 Participants
Number of Participants With Each Score on WHO 7-point Outcome Scale at Day 7 WHO ordinal scale 6	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Daily until day 14

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

Outcome measures

Outcome measures
Measure	Ruconest n=27 Participants 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. Ruconest: Patients will be randomized to Ruconest or Standard of Care	Standard of Care n=11 Participants SOC Ruconest: Patients will be randomized to Ruconest or Standard of Care
Time to Clinical Improvement	3.32 days Standard Error 0.32	4.91 days Standard Error 1.43

SECONDARY outcome

Timeframe: Daily until day 14.

Admission to ICU with invasive or non-invasive ventilation will be assessed.

Outcome measures

Outcome measures
Measure	Ruconest n=27 Participants 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. Ruconest: Patients will be randomized to Ruconest or Standard of Care	Standard of Care n=11 Participants SOC Ruconest: Patients will be randomized to Ruconest or Standard of Care
Invasive (Mechanical) or Non-invasive Ventilation Invasive (mechanical) ventilation	0 Participants	2 Participants
Invasive (Mechanical) or Non-invasive Ventilation Non-invasive ventilation	12 Participants	7 Participants

SECONDARY outcome

Timeframe: between D0 and D90

Amount of days the patient is hospitalized during participation in the study.

Outcome measures

Outcome measures
Measure	Ruconest n=27 Participants 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. Ruconest: Patients will be randomized to Ruconest or Standard of Care	Standard of Care n=11 Participants SOC Ruconest: Patients will be randomized to Ruconest or Standard of Care
Number of Days Hospitalized	5.38 days Standard Deviation 1.76	11.27 days Standard Deviation 16.01

Adverse Events

Ruconest

Serious events: 3 serious events

Other events: 23 other events

Deaths: 0 deaths

Standard of Care

Serious events: 2 serious events

Other events: 11 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Ruconest n=27 participants at risk 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. Ruconest: Patients will be randomized to Ruconest or Standard of Care	Standard of Care n=11 participants at risk SOC Ruconest: Patients will be randomized to Ruconest or Standard of Care
Blood and lymphatic system disorders Leukocytosis	11.1% 3/27 • Number of events 3 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	9.1% 1/11 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Gastrointestinal disorders Nausea	11.1% 3/27 • Number of events 3 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	0.00% 0/11 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Blood and lymphatic system disorders Leukopenia	7.4% 2/27 • Number of events 2 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	0.00% 0/11 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Cardiac disorders Tachycardia	7.4% 2/27 • Number of events 2 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	9.1% 1/11 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Gastrointestinal disorders Constipation	3.7% 1/27 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	9.1% 1/11 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Infections and infestations Sepsis	3.7% 1/27 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	9.1% 1/11 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Investigations Blood lactate dehydrogenase inc	14.8% 4/27 • Number of events 4 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	9.1% 1/11 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Investigations C-reactive protein increased	7.4% 2/27 • Number of events 2 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	9.1% 1/11 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Investigations Fibrin D dimer increased	18.5% 5/27 • Number of events 5 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	9.1% 1/11 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Investigations Serum ferritin increased	7.4% 2/27 • Number of events 2 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	9.1% 1/11 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Investigations Transaminitis	22.2% 6/27 • Number of events 6 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	0.00% 0/11 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Investigations Interleukin level increased	3.7% 1/27 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	9.1% 1/11 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Respiratory, thoracic and mediastinal disorders Hypoxia	7.4% 2/27 • Number of events 2 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	9.1% 1/11 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.1% 3/27 • Number of events 3 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	18.2% 2/11 • Number of events 2 • From signing off ICF till 90 days follow-up period Adverse event date were collected.

Additional Information

Anurag Relan, MD

Pharming Technologies BV

Phone: 0031 (0)71 5247400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Ruconest n=27 participants at risk 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. Ruconest: Patients will be randomized to Ruconest or Standard of Care	Standard of Care n=11 participants at risk SOC Ruconest: Patients will be randomized to Ruconest or Standard of Care
Metabolism and nutrition disorders Hyperglycemia	7.4% 2/27 • Number of events 2 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	0.00% 0/11 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Blood and lymphatic system disorders Leukocytosis	3.7% 1/27 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	0.00% 0/11 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Cardiac disorders Tachycardia	3.7% 1/27 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	0.00% 0/11 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Gastrointestinal disorders Gastroesophageal reflux disease	3.7% 1/27 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	0.00% 0/11 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Investigations Blood beta-D-glucan increased	0.00% 0/27 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	9.1% 1/11 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Investigations Fibrin D Dimer increased	3.7% 1/27 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	0.00% 0/11 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Investigations Transaminitis	3.7% 1/27 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	0.00% 0/11 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Nervous system disorders Encephalopathy	0.00% 0/27 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	9.1% 1/11 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Respiratory, thoracic and mediastinal disorders Chest pain	3.7% 1/27 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	0.00% 0/11 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/27 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	9.1% 1/11 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/27 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	9.1% 1/11 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Respiratory, thoracic and mediastinal disorders Pneumonia	3.7% 1/27 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	0.00% 0/11 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.7% 1/27 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	0.00% 0/11 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Respiratory, thoracic and mediastinal disorders Respiratory failure [Death]	0.00% 0/27 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	9.1% 1/11 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Vascular disorders Deep vein thrombosis	3.7% 1/27 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	0.00% 0/11 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Vascular disorders Hypotension	0.00% 0/27 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	9.1% 1/11 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.
Vascular disorders Shock	0.00% 0/27 • From signing off ICF till 90 days follow-up period Adverse event date were collected.	9.1% 1/11 • Number of events 1 • From signing off ICF till 90 days follow-up period Adverse event date were collected.