Intravenous Immunoglobulins for the Treatment of Covid-19 Patients: a Clinical Trial

September 11, 2020 updated by: Prof. Dr. Fridoon Jawad Ahmad, University of Health Sciences Lahore
The current project is based on the immunological studies covering the potential of disease induced immunoglobulins as treatment regime. We would be able to generate the concentrated antibodies specific against coronavirus (Covid-19). These antibodies can be used as serum therapy. Aside from a Covid-19 vaccine, antibodies from recovered patients could provide a short-term "passive immunization" to the disease. Those antibodies can be extracted from the blood serum of surviving patients and then injected into infected people. Passive immunization usually lasts for a few weeks or months, after which those borrowed or donated antibodies, get broken down by the host body within about 30 days. While drugs to treat patients with covid-19, and vaccines to prevent infection are being developed, a fast acting, stopgap serum therapy could be useful as a first aid for high-risk patients.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Emerging and re-emerging viruses are a significant threat to global public health. Since the end of 2019, Chinese authorities have reported a cluster of human pneumonia cases in Wuhan City, China and the disease was designated as coronavirus disease 2019 (COVID-19). These cases showed symptoms such as fever, dyspnea, and were diagnosed as viral pneumonia. Whole genome sequencing results show the causative agent is a novel coronavirus, which was initially named 2019-nCoV by World Health Organization (WHO). Later the International Committee on Taxonomy of Viruses (ICTV) officially designate the virus as SARS CoV-2 (Coronaviridae Study Group of the International Committee on Taxonomy of Viruses, 2020), although many virologists argue that HCoV-19 is more appropriate . As of 24 February 2020, 79,331 laboratory-confirmed cases have been reported to the WHO globally, with 77,262 cases in China, including 2,595 deaths. In addition, twenty-nine other countries have confirmed imported cases of SARS-CoV-2 infection raising great public health concerns worldwide. SARS-CoV-2 represents the seventh coronavirus that is known to cause human disease. Coronaviruses (CoVs) are a group of large and enveloped viruses with positive sense, single-stranded RNA genomes. Previously identified human CoVs that cause human disease include severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV) . SARS-CoV and MERS-CoV infection can result in life threatening disease and have pandemic potential. During 2002-2003, SARS-CoV initially emerged in China and swiftly spread to other parts of the world, causing > 8,000 infections and approximately 800 related deaths worldwide. In 2012, MERS-CoV was first identified in the Middle East and then spread to other countries. As of November 2019, a total of 2,494 MERS cases with 858 related deaths have been recorded in 27 countries globally. Notably, new cases of MERS-CoV infecting humans are still being reported recently. Both SARS-CoV and MERS-CoV are zoonotic pathogens originating from animals. Detailed investigations indicate that SARS-CoV is transmitted from civet cats to humans and MERS-CoV from dromedary camels to humans. The source of SARS-CoV-2, however, is still under investigation, but linked to a wet animal market. There is no specific antiviral treatment recommended for COVID-19, and no vaccine is currently available. The treatment is symptomatic, and oxygen therapy represents the major treatment intervention for patients with severe infection. Mechanical ventilation may be necessary in cases of respiratory failure refractory to oxygen therapy, whereas hemodynamic support is essential for managing septic shock. Although no antiviral treatments have been approved, several approaches have been proposed such as lopinavir/ritonavir (400/100 mg every 12 hours), chloroquine (500 mg every 12 hours), and hydroxychloroquine (200 mg every 12 hours). Alpha-interferon (e.g., 5 million units by aerosol inhalation twice per day) is also used. Preclinical studies suggested that remdesivir (GS5734) - an inhibitor of RNA polymerase with in vitro activity against multiple RNA viruses, including Ebola - could be effective for both prophylaxis and therapy of HCoVs infections. This drug was positively tested in a rhesus macaque model of MERS-CoV infection. One dose of 200 mL convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. Despite a lack of completed clinical trials, the FDA has granted this temporary authorization under its Investigational New Drug Applicants (eINDS) exemption, in light of the extent and nature of the current public health threat that COVID-19 represents. A number of pre-clinical and clinical trials around use of plasma from patients who have recovered are underway, however, and there are some promising signs that convalescent plasma could indeed be effective against SARS-CoV-2.

Apart from convalescent plasma, small scale concentrates of immunoglobulins prepared from convalescent plasma collections provide higher potency and greater consistency than individual units. The feasibility of production of large scale of diseases specific immunoglobulins concentrates can considered for longer term, based on the course of epidemic, access to large numbers of suitable plasma collections, and the available infrastructure for manufacturing such products under GMP.

• Convalescent plasma can be used for serum therapy but it has further limitations which include:

  • Separate plasma for separate blood groups: In case of plasma, it seems difficult to arrange the required blood groups separately for serum therapy, while immunoglobulins can be injected randomly to individual of different blood groups.
  • Serum Sickness & Blood Proteins reactogencity: Only 18% of plasma constitutes immunoglobulins required for passive immunization. Remaining portions contain proteins that pose to reactogenicity threat to patient safety.
  • Dose volume: In case of plasma therapy, 200-300ml of plasma required for single patient that depends upon number of recovered patients available. While in case of immunoglobulins used in virus therapy require only 3-5ml per day.
  • Risk of microbial contamination: As most portion of plasma contain proteins and proteins are more prone to contamination risk. It is difficult to handle the serum to maintain its sterility while immunoglobulins are far less prone to sterility issues.
  • Potency: Concentrated immunoglobulins are far more potent as it shows targeted response. In case of plasma, proteins fractions pose a delayed response.
  • Targeted Population: Plasma therapy is subjected to moderate to severe patients specially, while all effected individuals can take benefit of immunoglobulin therapy because dose of immunoglobulins can be controlled.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Fridoon J Ahmad, Ph.D

Study Locations

  • Pakistan
    • Punjab
      • Lahore, Punjab, Pakistan, 54000
        • University of Health Sciences
        • Contact:
        • Contact:
          • Fridoon Jawad Ahmad, PhD
        • Principal Investigator:
          • Fridoon Jawad Ahmad, PhD
        • Sub-Investigator:
          • Javed Akram, MBBS,FRCS,MRCP
        • Sub-Investigator:
          • Riffat Mehboob, PhD
        • Sub-Investigator:
          • Syed Amir Gilani, PhD
        • Sub-Investigator:
          • Muhammad Akram Tariq, PhD
        • Sub-Investigator:
          • Gibran Sheikh, PhD
        • Sub-Investigator:
          • Hassan Ahmad Khan, M.Phil

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age > 18 yrs
  • Both genders
  • Lab Confirmed COVID-19 infection by PCR or plasma positive of specific antibody against COVID-19
  • In hospital treatment ≥ 72 hours
  • Admitted patients
  • Mild to moderately severe patients

Exclusion Criteria:

  • Exist of other evidences that can explain pneumonia including but not limited to influenza A virus, influenza B virus, bacterial pneumonia, fungal pneumonia, noninfectious causes, etc.
  • Patients with respiratory diseases other than Covid-19 infection
  • Pregnant and breastfeeding women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control
They will not receive any intervention
Experimental: IVIG group
They will reveive intravenous immunoglobulin therapy
Biological: intravenous immunoglobulin therapy
It is passive immunization therapy. Plasma therapy is subjected to moderate to severe patients specially, while all effected individuals can take benefit of immunoglobulin therapy because dose of immunoglobulins can be controlled

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
In hospital days
Time Frame: 14 days or discharge
total number of days the patient remain in hospital
14 days or discharge
14 day mortality
Time Frame: 14 days
mortality if any in the study duration of 14 days
14 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
D-dimers
Time Frame: 7 days
reduction in D-dimers (< 250 ng/mL)
7 days
C-reactive protein
Time Frame: 7 days
reduction in C-Reactive protein (less than 10 mg/L)
7 days
Oxygen saturation
Time Frame: 7 days
improvement in oxygen saturation (pulse oximeter readings within range of 95 to 100%)
7 days
TNF alpha
Time Frame: 7 days
reduction in TNF alpha after IVIG treatment (upto 8.1 pg/mL)
7 days
IL-6
Time Frame: 7 days
reduction in IL-6 after IVIG treatment
7 days
Ferritin
Time Frame: 7 days
reduction in ferritin levels after IVIG treatment
7 days
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: 14 days
safety and tolerability
14 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Health Sciences Lahore

Collaborators

University of Lahore
Amson Vaccine and Pharma (Pvt) Limited

Investigators

  • Study Chair: Javed Akram, MBBS,FRCP,MRCP, Saglik Bilimleri Universitesi
  • Principal Investigator: Fridoon J Ahmad, Ph.D, Saglik Bilimleri Universitesi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

September 15, 2020

Primary Completion (Anticipated)

October 15, 2020

Study Completion (Anticipated)

November 15, 2020

Study Registration Dates

First Submitted

September 7, 2020

First Submitted That Met QC Criteria

September 11, 2020

First Posted (Actual)

September 14, 2020

Study Record Updates

Last Update Posted (Actual)

September 14, 2020

Last Update Submitted That Met QC Criteria

September 11, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UniversityHSL-IVIG

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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