Intravenous immunoglobulin therapy for ongoing COVID-19 in patients with B-cell issues

Intravenous Immunoglobulin Replacement Therapy for Persistent COVID-19 in Patients With B-cell Impairment: a Multicenter Randomized Controlled Trial

This study is testing whether intravenous immunoglobulin therapy can help people with B-cell issues who are still suffering from COVID-19 feel better.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 58 (estimated)
• Ages: 19 Years and up
• Sex: All
• Sponsor: Samsung Medical Center (other)
• Drugs / interventions: rituximab, CAR-T, chemotherapy
• Locations: 1 site (Seoul)
• Trial ID: NCT06159283 on ClinicalTrials.gov

What this trial studies

This multicenter, randomized controlled trial investigates the efficacy of intravenous immunoglobulin (IVIG) replacement therapy for patients suffering from persistent COVID-19 due to B-cell impairment. The study aims to provide passive immunization by utilizing SARS-CoV-2-specific antibodies from vaccinated plasma donors, focusing on their antiviral effects. Participants will be screened and randomly assigned to either the treatment group receiving IVIG or a control group receiving standard care. The goal is to assess the clinical efficacy of IVIG in alleviating symptoms of persistent COVID-19 in this specific patient population.

Who should consider this trial

Good fit: Ideal candidates include adults aged 19 and older diagnosed with persistent COVID-19 and B-cell impairment.

Not a fit: Patients who do not have B-cell impairment or those with mild COVID-19 symptoms may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly improve outcomes for patients with persistent COVID-19 who are unable to produce antibodies.

How similar studies have performed: While similar approaches have been explored, this specific focus on IVIG for persistent COVID-19 in B-cell impaired patients is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Voluntary written consent to participate in the trial
2. Age≥ 19 years
3. Diagnosed as COVID-19: the definitive diagnosis of COVID-19 will be made at a healthcare facility based on COVID-19 tests approved in Korea, such as reverse transcription polymerase chain reaction (RT-PCR), Xpert, film array, and rapid antigen test (RAT).
4. The diagnosis of persistent COVID-19 will be made following the criteria below:

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1. No improvement or worsening of symptoms/signs of active inflammation, such as fever, pneumonia, and dyspnea requiring oxygen, even after 2 weeks of the initial symptom onset or diagnosis of COVID-19 (persisting symptoms/signs at or after the third week of illness).
2. The day count for the disease course is based on the symptom onset or diagnosis date, whichever is earlier, with Day 1 being the date of symptom onset or diagnosis. The third week refers to the period including and following Day 15. For the purpose of day count calculation, self-test results using RAT are accepted.
3. Both symptoms and signs indicative of active inflammation must be present. This status corresponds to the Modified WHO clinical progression scale of ≥ 4.

   * Symptoms include at least one of the following.

     1. Fever of 37.8°C or higher lasting for \>48 h (determined based on self-measurement and statements from the patient or caregiver, with fevers persisting from Day 13 to Day 15 also accepted)
     2. Persistent cough despite taking appropriate expectorants and cough suppressants
     3. Dyspnea upon walking on a flat surface (modified Medical Research Council grade \>2) ② At least one of the following signs of active inflammation must be present.

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     1. Pulmonary infiltration suggestive of COVID-19 observed in chest radiograph or computed tomography scan findings. Findings may vary, from ground-glass opacities to patchy consolidation, and are determined by the clinician or radiologist.
     2. Decreased oxygen saturation (PaO2/FiO2 ≤300 mmHg, SpO2 ≤92%, or PaO2 ≤63%) 5. Cases of patients with B-cell impairment:

(1) Patients with B-cell lineage hematologic malignancies, such as B-cell lymphoma or multiple myeloma, who are presumed to have impaired B-cell function owing to B-cell targeting chemotherapy (i.e., those receiving rituximab, CAR-T, Bispecific T-cell engager therapies), or second-line or higher treatments, such as autologous stem cell transplantation (AutoPBSCT) (2) Patients suffering from diseases known to result in B-cell depletion, such as Good's syndrome associated with thymoma (3) Cases of patients with a congenital primary immunodeficiency who have reduced antibody formation and have not undergone IVIG replacement in the past 3 months.

Among these, those who received B-cell targeting chemotherapy within the past 3 months are eligible for enrollment based on clinical criteria, but other patients must confirm the reduction of peripheral B cells to \<1% via flow cytometry to be eligible for enrollment.

Exclusion Criteria:

1. Difficulty controlling the underlying disease or life expectancy of \<3 months even after COVID-19 is successfully treated.
2. T-cell impairment.

(1)T-cell suppressive drugs (e.g., cyclosporine, tacrolimus) cannot be suspended owing to organ transplantation or autoimmune disorder.

(2) Patients with human immunodeficiency virus (HIV) infection with a CD4 T-cell count \<500 cells/μL or persistent detection of HIV viral RNA in the blood.

3\. IVIG or COVID-19 convalescent plasma therapy within 3 months of screening 4. History of serious reaction or hypersensitivity to blood, blood products, blood-derived products, IVIG, and IgG 5. Immunoglobulin A (IgA) deficiency or IgA antibodies present 6. Uncontrolled hypertension (systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg) 7. Hemolytic anemia, hemorrhagic anemia 8. Impaired cardiac function \[New York Heart Association Functional Class Ⅲ or IV\] 9. High risk for thrombosis/embolism clinically owing to a history of cerebrovascular and cardiovascular disorders, thrombosis, or embolism 10. Cases of pregnant or breastfeeding women 11. Current participation in another clinical trial related to COVID-19 drugs 12. Cases of participants that are inappropriate to participate in the trial based on the investigator's discretion

Where this trial is running

Seoul

• Jaehoon Ko — Seoul, South Korea (RECRUITING)

Study contacts

• Principal investigator: Jaehoon Ko, Ph,MD — Samsung Medical Center
• Study coordinator: Jaehoon Ko, Ph,MD

Conditions: COVID-19