Clinical trial NCT04498325: Evaluating the Effect of NT-I7, a Long Acting Interleukin-7, to Increase Lymphocyte Counts and Enhance Immune Clearance of SARS-CoV-2 (COVID-19)
Official title: A Phase I and Pilot Study Evaluating the Effect of NT-I7, a Long Acting Interleukin-7, to Increase Lymphocyte Counts and Enhance Immune Clearance of SARS-CoV-2
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: COVID-19
SARS-CoV-2
Keywords: COVID-19
SARS-CoV-2
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: NeoImmuneTech
First posted: 2020-08-04
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study will open as a phase I study to test three different dose levels of NT-I7. Once a safe tolerated dose is established, the pilot portion of the study will be activated wherein participants will be randomized on a 1:1 basis to receive a single injection of NT-I7 (at the safe tolerated dose) or placebo.
Primary purpose: TREATMENT

Brief summary: Lymphopenia is common in patients with COVID-19 and is associated with worse clinical outcomes. NT-I7 is a long-acting human interleukin-7 (IL-7) that has been shown to increase absolute lymphocyte count (ALC) and CD4+ and CD8+ T cell counts with a well-tolerated safety profile in humans. In this study, patients who have tested positive for SARS-CoV-2 by PCR testing without severe disease and with ALC \<1500 cells/mm3 will be enrolled.


Eligibility criteria: Inclusion Criteria:

* Tested PCR positive for SARS-CoV-2by nasopharyngeal swab, oropharyngeal swab, or saliva.
* Mild COVID-19, defined as WHO Ordinal Scale \<4 .
* Respiratory rate \< 20 bpm, HR \< 90 bpm, and SpO2 \> 93% on room air at sea level.
* Absolute lymphocyte count (ALC) \< 1500 cells/mm3 at the time of screening.
* AST/ALT ≤ 3.0 x ULN, total bilirubin ≤ 1.5 x ULN (except if due to Gilbert's syndrome).

  -≥ 18 years of age.
* First day of treatment must be no more than 10 days from onset of COVID-19 symptoms.
* Must be willing to be closely monitored in the hospital or in an alternate setting (e.g. clinical trial unit) for at least the first 7 days (±2 days allowed) following NT-I7/placebo injection.
* Individuals of reproductive potential must agree to either abstinence or use of at least one study-approved form of contraception when engaging in sexual activities that can result in pregnancy from the time of screening through 60 days for female and 120 days for male after study agent administration. Acceptable forms of contraception for this study are male or female condoms, diaphragms or cervical caps with a spermicide, or non-hormonal intrauterine devices.
* Patients with factors or concomitant illness associated with higher risk of mortality due to COVID-19 (such as older age, hypertension, diabetes, and/or COPD) are eligible.
* Able to understand and willing to sign an IRB approved written informed consent document.

Exclusion Criteria:

* Receiving any other investigational agents which may affect patient's lymphocyte counts. Note: There is no evidence that chloroquine or hydroxychloroquine could affect lymphocyte counts. Thus, chloroquine or hydroxychloroquine use is not an exclusion criteria for this study. Additionally, it is permissible for potential participants to have received investigational or off-label agents for COVID-19 prior to or during study participation.
* Pregnant or breastfeeding women are excluded from this study because NT-I7 has not been evaluated regarding its potential for teratogenic or abortifacients effects. There is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drug; therefore, breastfeeding should be discontinued if the mother is treated with NT-I7.
* Transferred from ICU to the floor.
* Requiring dialysis.
* Shortness of breath or known hypoxia (defined as PaO2/FiO2 ≤ 300 mmHg), or signs of serious lower airway disease.
* Evidence of ARDS, SIRS/shock, or cardiac failure.
* Elevated inflammatory markers such as CRP \> 2 x ULN, LDH \> 2 x ULN, D-dimer \> 2 x ULN, ferritin \> ULN, or IL-6 \> ULN (when available).
* Any established diagnosis of autoimmune disease requiring systemic treatment EXCEPT for vitiligo or endocrine disease (such as diabetes, thyroid disease, and adrenal disease) controlled by replacement therapy.
* Receipt of live attenuated vaccine within 30 days before the study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guérin (BCG), Zoster, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist) are live attenuated vaccines and are not allowed.

Primary outcomes:
measure: Safe and tolerable dose of NT-I7 (Phase I only)
timeFrame: Completion of DLT assessment window of Phase I portion of study (estimated to be 8 months)
measure: Percent change in absolute lymphocyte count (ALC)
timeFrame: From baseline to Day 14
Secondary outcomes:
measure: Percent change in absolute lymphocyte count (ALC)
timeFrame: From baseline through Day 21
measure: Change in SARS-CoV-2 viral load
timeFrame: From baseline to Day 7
measure: Change in SARS-CoV-2 viral load
timeFrame: From baseline to Day 14
measure: COVID-19 Symptom severity as measured by WHO Ordinal Scale for clinical improvement
timeFrame: From baseline, day 7, day 14, and day 21
measure: Time to resolution of COVID-19 symptoms
timeFrame: From baseline through Day 21
measure: Incidence of treatment-emergent adverse events
timeFrame: From baseline through Day 21
measure: Number of participants by PCR result status (positive or negative)
timeFrame: -From baseline to Day 7
measure: Number of participants by PCR result status (positive or negative)
timeFrame: From baseline to Day 14
Other outcomes:
Locations:
Study officials:
affiliation: Washington University School of Medicine
name: Jian Campian, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: