Nasal Administration of Anti-CD3 Monoclonal Antibody (Foralumab) Reduces Lung Inflammation and Blood Inflammatory Biomarkers in Mild to Moderate COVID-19 Patients: A Pilot Study

Abstract

Background: Immune hyperactivity is an important contributing factor to the morbidity and mortality of COVID-19 infection. Nasal administration of anti-CD3 monoclonal antibody downregulates hyperactive immune responses in animal models of autoimmunity through its immunomodulatory properties. We performed a randomized pilot study of fully-human nasal anti-CD3 (Foralumab) in patients with mild to moderate COVID-19 to determine if its immunomodulatory properties had ameliorating effects on disease.

Methods: Thirty-nine outpatients with mild to moderate COVID-19 were recruited at Santa Casa de Misericordia de Santos in Sao Paulo State, Brazil. Patients were randomized to three cohorts: 1) Control, no Foralumab (n=16); 2) Nasal Foralumab (100ug/day) given for 10 consecutive days with 6 mg dexamethasone given on days 1-3 (n=11); and 3) Nasal Foralumab alone (100ug/day) given for 10 consecutive days (n=12). Patients continued standard of care medication.

Results: We observed reduction of serum IL-6 and C-reactive protein in Foralumab alone vs. untreated or Foralumab/Dexa treated patients. More rapid clearance of lung infiltrates as measured by chest CT was observed in Foralumab and Foralumab/Dexa treated subjects vs. those that did not receive Foralumab. Foralumab treatment was well-tolerated with no severe adverse events.

Conclusions: This pilot study suggests that nasal Foralumab is well tolerated and may be of benefit in treatment of immune hyperactivity and lung involvement in COVID-19 disease and that further studies are warranted.

Keywords: COVID-19; SARS-CoV-2; anti-CD3; foralumab; immune responses.

Figure 1

Clinical Study Design. Symptomatic patients were consented and randomized on day -2. Blood and nasopharyngeal swab collection, CT scans and medical exam was also performed at day -2. *Eligibility was confirmed on day 0 (SARS-CoV-2 PCR positive results, infectious disease negative results). Foralumab treatment started at day 1 for 10 days. Dexamethasone (6mg/day) was given on days 1-3 to Foralumab/Dexa group. PRO data was collected daily during treatment (day 1 to day 10) and symptomatology was accessed during medical exam at the beginning and completion of study (day -2 and day 13). Blood collection for biomarkers follow-up was performed at day 5 and day10. Patient returned to the hospital for clinical exam and CT scan follow up on day 13. ❖ Symptomatology and drug use assessment. CT, computerized tomography; PRO, patient reported outcome.

Figure 2

Blood inflammatory markers IL-6 and C-reactive protein. Serum quantification and percentage of reduction of (A) IL-6 and (B) C-reactive protein. Linear regression was used to compare three-group comparison of each time point. A linear mixed model with a random intercept was used to baseline (day -2) comparison. Percent of baseline was compared using Wilcoxon rank sum test. p= <0.05. IL, Interleukin, CRP, c-reactive protein, Dexa, dexamethasone.

Figure 3

Lung CT Scan: CT chest in COVID-19 patients by treatment group. I-II: Axial images in a control patient shows widespread ground glass opacity (anterior and posterior segments of bilateral upper and right middle lobes) two days prior to treatment (I) showing significant progression at 13 days follow up (II). III-IV: Axial images in a patient treated with Foralumab/Dexa showing both widespread ground glass opacity in the anterior and posterior segments and consolidation in both lower lobes (III) demonstrating partial resolution on the 13 follow up day scan (IV). V-VI: Axial images in a patient who received Foralumab showing ground glass opacity of posterior segments of lungs (V) demonstrating interval resolution on 13 follow up day scan (VI). Dexa, dexamethasone.