Octagam 10% Therapy in COVID-19 Patients With Severe Disease Progression

Phase 3

Completed

• Conditions: Covid-19
• Interventions: Biological: Octagam 10%; Other: Saline Solution

• Registration Number: NCT04400058
• Lead Sponsor: Octapharma

Brief Summary

This is a randomized, double-blind, placebo-controlled, multicenter, Phase 3 study to evaluate if high-dose Octagam 10% therapy can stabilize or improve clinical status in patients with severe Coronavirus disease

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-05-21
• Study First Submitted QC: 2020-05-21
• Study First Posted: 2020-05-22
• Study Start: 2020-06-01
• Primary Completion: 2022-02-01
• Study Completion: 2022-02-01
• Results First Submitted: 2023-12-11
• Status Verified: 2024-01
• Results First Submitted QC: 2024-01-16
• Last Update Submitted: 2024-01-16
• Results First Posted: 2024-01-18
• Last Update Posted: 2024-01-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 207

Inclusion Criteria

1. Adult aged ≥18years old
2. Provide voluntary, fully informed written and signed consent before any study-related procedures are conducted
3. Able to understand and comply with the relevant aspects of the study protocol
4. Laboratory (RT-PCR) confirmed COVID-19 infection on throat swab and/or sputum and/or lower respiratory tract samples
5. Hospitalized with a resting room-air SpO2 of ≤93% or PaO2/FiO2 ratio <300mmHg. Measurement can be taken from documented source records in the 24 hours prior to screening
6. Chest imaging confirming lung involvement

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Exclusion Criteria

1. Existence of other evidence that can explain pneumonia including but not limited to: Influenza A virus, influenza B virus, bacterial pneumonia (as suggested by the combined clinical picture, radiological findings and known laboratory results [eg, elevated procalcitonin >0.5ng/mL and concomitant neutrophilia]), known fungal pneumonia, suspected fungal pneumonia based on compromised immune system with a history of past fungal infections, noninfectious causes, etc.

2. Known history of serious allergic reactions, including anaphylaxis, to IVIG or its preparation components

3. Subjects with a history of thromboembolic event (TEE) within the last 12 months, such as deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, transient ischemic attack, peripheral artery disease (Fontaine IV)

4. Subjects with an underlying medical condition that can lead to hypercoagulable states and hyperviscosity such as antithrombin III deficiency, Factor V Leiden, Protein C deficiency, antiphospholipid syndrome and malignancy

5. Known history of selective IgA deficiency with antibodies against IgA

6. Subjects with conditions such as human immunodeficiency virus (HIV) infection, known acute or chronic hepatitis B or C (HBsAg positive or HCV ribonucleic acid (RNA) PCR positive or currently treated with antivirals), pulmonary fibrosis, elevated procalcitonin (> 0.5) with concomitant neutrophilia (elevated polys), heparin induced thrombocytopenia (HIT), and moderate to severe renal dysfunction (per investigator discretion based on estimated glomerular filtration rate [eGFR] <59 mL/min/1.73 m2, as defined by KDIGO Clinical Practice Guideline):

   • Moderately reduced GFR (G3a): GFR = 45 to 59 ml/min/1.73 m2
   • Moderately reduced GFR (G3b): GFR = 30 to 44 ml/min/1.73 m2
   • Severely reduced GFR (G4): GFR = 15 to 29 ml/min/1.73 m2
   • Kidney failure (G5): GFR <15 ml/min/1.73 m2

7. Currently requiring IMV (invasive mechanical ventilation or having received IMV during the last 30 days

8. Known clinically significant preexisting lung, heart, or neuromuscular disease that, in the investigator's opinion, would impact subject's ability to complete study or may confound the study results

9. Body weight >125 kg

10. Women who are pregnant or breast-feeding

11. Subjects who received COVID-19 convalescent plasma, IVIG products, anti-interleukin agents (eg, Tocilizumab), or interferons for their COVID-19 disease before enrollment or plan to receive this treatment during the course of the study

12. Enrolled in other experimental interventional studies or taking experimental medications (ie, convalescent plasma). Diagnostic studies can be allowed if the anticipated total blood volume to be drawn across both studies and for therapeutic purposes does not exceed 450 mL over any 8-week period.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Octagam 10%	Octagam 10%	Octagam 10%
Saline Solution	Saline Solution	Placebo

Primary Outcome Measures

Name	Time	Method
Proportion of Subjects Reaching Stabilization or Improvement in Clinical Status at Day 7	7 days	Proportion of subjects reaching stabilization or improvement in clinical status in at least one category on a 6-point clinical status scale.; Clinical status categories will be defined as: 1. Hospital discharge or meet discharge criteria (discharge criteria are defined as clinical recovery, i.e. no fever, respiratory rate, oxygen saturation return to normal, and cough relief).; 2. Hospitalization, not requiring supplemental oxygen.; 3. Hospitalization, requiring supplemental oxygen (but not NIV/HFNC).; 4. ICU/hospitalization, requiring NIV/HFNC therapy, as defined by A-a Gradient ≥150mmHg.; 5. ICU, requiring Extracorporeal Membrane Oxygenation (ECMO) and/or IMV.; 6. Death.

Secondary Outcome Measures

Name	Time	Method
Length of Hospital Stay (Time to Discharge)	33 days	Median length of hospital stay in subjects treated with Octagam 10%, compared to those that received placebo from randomization through Day 33
Number of Subjects With Severe Disease Progression	33 days	Number of subjects who experienced severe disease progression while treated with Octagam 10% compared to those that received placebo at Day 33. Severe disease progression is defined as subjects requiring extracorporeal membrane oxygenation, mechanical ventilation and/or died through day 33.
ICU Stay Length	33 days	Average length of ICU stay in subjects treated with Octagam 10% compared to those that received placebo from randomization through Day 33.
Number of Subjects Reaching Stabilization or Improvement In Clinical Status at Day 14	14 days	Number of subjects with maintenance or improvement by at least one category on the 6-point clinical status scale on Day 14.; Clinical status categories will be defined as: 1. Hospital discharge or meet discharge criteria (discharge criteria are defined as clinical recovery, i.e. no fever, respiratory rate, oxygen saturation return to normal, and cough relief).; 2. Hospitalization, not requiring supplemental oxygen.; 3. Hospitalization, requiring supplemental oxygen (but not NIV/HFNC).; 4. ICU/hospitalization, requiring NIV/HFNC therapy, as defined by A-a Gradient ≥ 150 mmHg.; 5. ICU, requiring Extracorporeal Membrane Oxygenation (ECMO) and/or IMV.; 6. Death.
Cumulative Duration of Invasive Mechanical Venitlation (IMV)	33 days	Duration of invasive mechanical ventilation in subjects treated with Octagam 10% compared to placebo from randomization through Day 33
Cumulative Mortality Rate Through Day 33	33 days	Cumulative mortality in subjects treated with Octagam 10% compared to those that received placebo at Day 33

Trial Locations

Locations (1)

Octapharma Research Site; 🇺🇦 Kremenchuk, Ukraine