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)

NCT ID: NCT04498325

Last Updated: 2021-08-05

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-31
• Study Completion Date: 2022-04-30

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.

Conditions

COVID-19; SARS-CoV-2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

NT-I7 (Phase I)

• In the phase I study, 3 dose levels of NT-I7 are planned. Dosing will be staggered such that there will be a minimum of 72 hours between the dosing of one participant and the dosing of the next participant
• NT-I7 will be given by intramuscular injection on Day 0
• Participants will also be given standard of care treatment for COVID-19

Group Type: EXPERIMENTAL

NT-I7

Intervention Type: DRUG

Supplied by study

Blood for research purposes

Intervention Type: PROCEDURE

Prior to injection (Day 0), Day 7, and Day 14

Blood for pharmacokinetic samples

Intervention Type: PROCEDURE

-Phase I only: 1-2 hours prior to dosing, 6 hours after dosing, 24 hours after dosing, Day 7, Day 14, and Day 21

Nasopharyngeal, oropharyngeal, or saliva swab

Intervention Type: PROCEDURE

-Prior to study treatment, Day 4(optional), Day 7, and Day 14

Blood for anti-drug antibody (ADA)

Intervention Type: PROCEDURE

Baseline, Day 7, Day 14, Day 21, Day 60, and Day 90. Participants with ADA positivity on Day 90 will be monitored every 90 days until antibody level returns to baseline

NT-I7 (Pilot)

• NT-I7 (dose determined by Phase I portion of study) will be given by intramuscular injection on Day 0
• Participants will also be given standard of care treatment for COVID-19

Group Type: EXPERIMENTAL

NT-I7

Intervention Type: DRUG

Supplied by study

Blood for research purposes

Intervention Type: PROCEDURE

Prior to injection (Day 0), Day 7, and Day 14

Nasopharyngeal, oropharyngeal, or saliva swab

Intervention Type: PROCEDURE

-Prior to study treatment, Day 4(optional), Day 7, and Day 14

Blood for anti-drug antibody (ADA)

Intervention Type: PROCEDURE

Baseline, Day 7, Day 14, Day 21, Day 60, and Day 90. Participants with ADA positivity on Day 90 will be monitored every 90 days until antibody level returns to baseline

Placebo (Pilot)

• Placebo will be given by intramuscular injection on Day 0
• Participants will also be given standard of care treatment for COVID-19

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Supplied by study

Blood for research purposes

Intervention Type: PROCEDURE

Prior to injection (Day 0), Day 7, and Day 14

Nasopharyngeal, oropharyngeal, or saliva swab

Intervention Type: PROCEDURE

-Prior to study treatment, Day 4(optional), Day 7, and Day 14

Blood for anti-drug antibody (ADA)

Intervention Type: PROCEDURE

Baseline, Day 7, Day 14, Day 21, Day 60, and Day 90. Participants with ADA positivity on Day 90 will be monitored every 90 days until antibody level returns to baseline

Interventions

NT-I7

Supplied by study

Intervention Type: DRUG

Placebo

Supplied by study

Intervention Type: DRUG

Blood for research purposes

Prior to injection (Day 0), Day 7, and Day 14

Intervention Type: PROCEDURE

Blood for pharmacokinetic samples

-Phase I only: 1-2 hours prior to dosing, 6 hours after dosing, 24 hours after dosing, Day 7, Day 14, and Day 21

Intervention Type: PROCEDURE

Nasopharyngeal, oropharyngeal, or saliva swab

-Prior to study treatment, Day 4(optional), Day 7, and Day 14

Intervention Type: PROCEDURE

Blood for anti-drug antibody (ADA)

Baseline, Day 7, Day 14, Day 21, Day 60, and Day 90. Participants with ADA positivity on Day 90 will be monitored every 90 days until antibody level returns to baseline

Intervention Type: PROCEDURE

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

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NeoImmuneTech

INDUSTRY

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jian Campian, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

202009065

Identifier Type: -

Identifier Source: org_study_id