A Trial of NT-I7 in COVID-19 (SPESELPIS)

A Double-blind, Randomized, Placebo-controlled, Phase 1, Single-dose, Dose-escalating Trial of Long-acting Recombinant Human IL-7 (NT-I7) for COVID-19

The main purposes of this study is to determine the following in participants with mild coronavirus disease 2019 (COVID-19):

• Safety of a single dose of NT-I7
• The immunological effects of NT-I7 on peripheral lymphocyte counts in COVID-19 patients.

This is a multisite, double-blind, randomized, placebo-controlled, dose-escalating, phase 1 trial of NT-I7 with standard of care (SOC) versus placebo with SOC to evaluate the safety and efficacy of NT-I7 in adults with mild coronavirus disease 2019 (COVID-19). After determination of eligibility and baseline assessment, a single dose of the study agent (NT-I7 or placebo) will be administered after 1:1 randomization, along with SOC. Research blood collection will occur at baseline, days 3, 7, 14, 30, 60 and 90 days after administration. Primary and secondary evaluations will include assessment of adverse events (AEs), absolute lymphocyte count (ALC), and trajectory of other lymphocytes subsets: CD4, CD8, natural killer (NK), B, and mucosal-associated-invariant T (MAIT) cells. The final study visit will be at day 90 after the study agent administration. The investigators hypothesize that NT-I7 is safe for administration and preserves lymphocyte homeostasis in patients with mild COVID-19.

Inclusion Criteria:

• Individuals must meet all of the following criteria to be included in the study:
• Laboratory-confirmed SARS-CoV-2 infection as determined by either a documented positive molecular assay/ other commercial or public health assay in any specimen collected < 5 days prior to screening or a documented positive molecular assay ≥ 5 days prior to screening and confirmed by polymerase chain reaction (PCR) at screening.
• Illness of any duration with oxygen saturation > 93% at room air, heart rate ≤ 100 beats per minute at rest, and no evidence of respiratory distress with respiration rate < 20 breaths per minute.
• Able to provide informed consent.
• Aged ≥ 19 and ≤ 75 years.
• Absolute Lymphocyte Count <1,500 lymphocytes/µL.
• Avoid becoming pregnant or impregnate a partner through 90 days after study agent administration. Females must agree to 2 methods of contraception, and males to at least one method of contraception.
• Not participate in any other clinical trial for an investigational therapy through day 30.

Exclusion Criteria:

• Moderate to severe hypoxic respiratory failure requiring supplemental oxygen at rest, mechanical ventilation, ECMO, or any other noninvasive ventilation modality.
• CRP >15 mg/L or D-dimer > 0.75 µg/mL.
• Estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73m2, or requiring dialysis.
• AST/ALT > 3-times ULN, or total bilirubin > 1.5 times ULN (except if due to Gilbert's syndrome).
• Pregnancy or breastfeeding.
• Use of systemic corticosteroids or immunomodulant within 4 weeks prior to screening.
• Receipt of an investigational agent or investigational use of a licensed agent within 16 weeks prior to screening.
• HIV infection or underlying history of known or unknown primary or acquired immunodeficiency associated with lymphopenia and/or recurrent opportunistic infections.
• Autoimmune disease requiring systemic treatment EXCEPT for vitiligo or endocrine disease (such as diabetes, thyroid disease, and adrenal disease) controlled by replacement therapy.
• Malignancy requiring treatment 1 year prior to screening.