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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Double-Blind NT-I7
* Drug: Double-Blind Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NT-I7<br>NT-I7 will be administered once by IM injection within 24 hours of baseline (day 0). The treatment course pursued in all enrolled participants will be a single dose. Dosing will be staggered with at least 72 hours between each study participant. | Drug: Double-Blind NT-I7<br>* Administered by intramuscular (IM) injection<br>* Other names: efineptakin alfa;|
| Placebo Comparator: Placebo<br>Placebo will be administered once by IM injection within 24 hours of baseline (day 0). The treatment course pursued in all enrolled participants will be a single dose. Dosing will be staggered with at least 72 hours between each study participant. | Drug: Double-Blind Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the safety of a single dose of NT-I7 in a dose escalation fashion | Assessment of the number and severity of AEs possibly, probably, or definitely related to study drug evaluated at 7 and 30 days. | Up to approximately 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the immunological effects of NT-I7 cumulatively for all doses on peripheral lymphocyte counts in COVID-19 patients. | Assessment of the trajectory of ALC, CD4, CD8, NK, B, and MAIT cells measured at days 7, 14 and 30 after administration of NT-I7 or placebo compared to baseline values. | Up to approximately 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NT-I7 (efineptakin alfa, rhIL-7-hyFc), COVID-19