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

Efficacy and Safety of Octagam 10% Therapy in COVID-19 Patients With Severe Disease Progression

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

Study Overview

• Status: Completed
• Conditions: Covid-19
• Intervention / Treatment: Other: Saline Solution; Biological: Octagam 10%

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Ivanovo, Russian Federation, 153025
    • Octapharma Research Site
  • Moscow, Russian Federation, 111539
    • Octapharma Research Site
  • Moscow, Russian Federation, 129301
    • Octapharma Research Site
  • Ryazan', Russian Federation, 390000
    • Octapharma Research Site
• Ukraine
  • Ivano-Frankivs'k, Ukraine, 76007
    • Octapharma Research Site
  • Kharkiv, Ukraine, 61096
    • Octapharma Research Site
  • Kremenchuk, Ukraine, 39623
    • Octapharma Research Site
• United States
  • Alabama
    • Sheffield, Alabama, United States, 35660
      • Octapharma Research Site
  • California
    • Loma Linda, California, United States, 92354
      • Octapharma Research Site
    • Loma Linda, California, United States, 92357
      • Octapharma Research Site
    • Newport Beach, California, United States, 92663
      • Octapharma Research Site
    • Orange, California, United States, 92868
      • Octapharma Research Site
    • San Diego, California, United States, 92123
      • Octapharma Research Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Octapharma Research Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Octapharma Research Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Octapharma Research Site
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Octapharma Research Site
  • Michigan
    • Midland, Michigan, United States, 48670
      • Octapharma Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Octapharma Research Site
  • North Dakota
    • Minot, North Dakota, United States, 58701
      • Octapharma Research Site
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Octapharma Research Site
  • Texas
    • Tyler, Texas, United States, 75708
      • Octapharma Research Site

Participation Criteria

Eligibility Criteria

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

Description

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

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Octagam 10%	Biological: Octagam 10%; Octagam 10%, 2 g/kg divided by 4 days (0.5 g/kg/day), administered by intravenous infusion over approximately 2 hours per day over 4 consecutive days
Placebo Comparator: Saline Solution; Placebo	Other: Saline Solution; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Reaching Stabilization or Improvement in Clinical Status at Day 7	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: 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).; Hospitalization, not requiring supplemental oxygen.; Hospitalization, requiring supplemental oxygen (but not NIV/HFNC).; ICU/hospitalization, requiring NIV/HFNC therapy, as defined by A-a Gradient ≥150mmHg.; ICU, requiring Extracorporeal Membrane Oxygenation (ECMO) and/or IMV.; Death.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Hospital Stay (Time to Discharge)	Median length of hospital stay in subjects treated with Octagam 10%, compared to those that received placebo from randomization through Day 33	33 days
Number of Subjects Reaching Stabilization or Improvement In Clinical Status at Day 14	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: 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).; Hospitalization, not requiring supplemental oxygen.; Hospitalization, requiring supplemental oxygen (but not NIV/HFNC).; ICU/hospitalization, requiring NIV/HFNC therapy, as defined by A-a Gradient ≥ 150 mmHg.; ICU, requiring Extracorporeal Membrane Oxygenation (ECMO) and/or IMV.; Death.	14 days
Cumulative Duration of Invasive Mechanical Venitlation (IMV)	Duration of invasive mechanical ventilation in subjects treated with Octagam 10% compared to placebo from randomization through Day 33	33 days
Number of Subjects With Severe Disease Progression	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.	33 days
ICU Stay Length	Average length of ICU stay in subjects treated with Octagam 10% compared to those that received placebo from randomization through Day 33.	33 days
Cumulative Mortality Rate Through Day 33	Cumulative mortality in subjects treated with Octagam 10% compared to those that received placebo at Day 33	33 days

Collaborators and Investigators

• Sponsor: Octapharma

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): February 1, 2022
• Study Completion (Actual): February 1, 2022

Study Registration Dates

• First Submitted: May 21, 2020
• First Submitted That Met QC Criteria: May 21, 2020
• First Posted (Actual): May 22, 2020

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; COVID-19; Disease Progression; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: GAM10-10

Drug and device information, study documents

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