Efficacy and Safety of Intravenous Immunoglobulin as Add-on to Standard of Care vs Standard of Care Alone in COVID-19 Patients with Severely Impaired B-cell Function

The primary objective is to evaluate the efficacy of intravenous immunoglobulin as an add-on to standard of care compared to standard of care alone in patients with COVID-19 and severely impaired B-cell function who are non-responsive to vaccination. This assessment focuses on clinical recovery and the clearance of RNAemia by Day 28 after randomization. Secondary objectives include:

• Evaluation of efficacy regarding clinical improvement and RNAemia clearance at Day 10.
• Assessment of sustained recovery and viral infection clearance.
• Evaluation of improved clinical status at Day 10 and Day 28.
• Prevention of progression to severe disease up to Day 28.
• Assessment of safety profiles for the add-on therapy.

The sponsor did not provide information regarding the total number of participants. The study population consists of adult patients, including both males and females, with COVID-19 and severely impaired B-cell function. Eligible participants must have experienced symptomatic infection for at least seven days and demonstrate SARS-CoV-2 RNA in blood plasma via RT-PCR. Inclusion requires a history of full vaccination and anti-SARS-CoV-2 Spike IgG levels below the detection limit for seropositivity. The immunocompromised status may result from hematological malignancy, rejection therapy following solid organ transplantation, or anti-CD20 monoclonal antibody treatment. Participants must provide informed consent and, for those of childbearing potential, adhere to specific contraceptive requirements.

This phase 2, randomized, open-label trial is designed to evaluate the efficacy and safety of intravenous immunoglobulin as an add-on to standard of care in patients with COVID-19 and severely impaired B-cell function. Participants are randomized to receive either the investigational product, Privigen, or standard of care alone, which may include comparators such as remdesivir or nirmatrelvir. The study begins with a screening period to assess eligibility, including verification of symptomatic COVID-19, SARS-CoV-2 RNA detection via RT-PCR, and specific immunocompromised status. Following randomization, the primary endpoint is assessed at day 28, focusing on clinical recovery and the clearance of RNAemia. Secondary assessments include monitoring for clinical improvement at day 10 and evaluating sustained recovery at day 90 and day 180. Throughout the study, adverse events are monitored to ensure safety. The total duration of participant involvement extends through the final follow-up visits, and early termination may occur based on investigator assessment or safety requirements.

The experimental treatment consists of Privigen, which contains human normal immunoglobulin. This medication is provided as a 100 mg/ml solution for infusion and is administered via intravenous infusion at a dosage of 40 g.

The comparator treatments include Veklury, containing remdesivir. This product is supplied as a 100 mg powder for concentrate for solution for infusion and is administered through intravenous infusion at a dose of 200 mg.

The comparator treatment also includes Paxlovid, which contains nirmatrelvir. This medication is administered as film-coated tablets for oral use at dosages of 200 mg or 600 mg.

The primary efficacy endpoint is the proportion of participants achieving clinical recovery and RNAemia clearance by Day 28 after randomization. Clinical recovery is defined as a score of 0 or 1 on the WHO Clinical Progression Scale. Clearance is defined as the absence of detectable SARS-CoV-2 RNA in blood plasma at Day 28, provided no additional SARS-CoV-2 directed treatment is administered beyond standard of care.

Secondary efficacy parameters include:

• The proportion of participants achieving clinical improvement, defined as a reduction in the WHO Clinical Progression Scale score of ≥1, and no detectable SARS-CoV-2 RNA in blood plasma at Day 10 after randomization.
• The proportion of participants with sustained clinical recovery, defined by a WHO Clinical Progression Scale score of 0 or 1 and no baseline SARS-CoV-2 strain RNA in blood plasma or nasopharyngeal sample, at days 90 and 180.
• A rank-based comparison of the 10-category ordinal WHO Clinical Progression Scale score as assessed by the investigator at days 10 and 28 after randomization.
• The proportion of participants experiencing severe COVID-19, defined as a score of ≥6 on the WHO Clinical Progression Scale, up to and by Day 28 after randomization.