Cyclosporine in Patients With Moderate COVID-19

Phase I Trial for the Prevention of Cytokine Release Syndrome (CRS) With Cyclosporine in Patients With Moderate COVID-19

Phase 1 safety study to determine the tolerability, clinical effects, and changes in laboratory parameters of short course oral or IV cyclosporine (CSA) administration in patients with COVID-19 disease requiring oxygen supplementation but not requiring ventilator support.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Cyclosporine

Detailed Description

Our overall hypothesis is that CSA is safe in this patient population and that it will have antiviral and anti-cytokine effects as measured in laboratory tests.

The initial dose will be 9 mg/kg/day oral divided q12h or 3 mg/kg/day by continuous IV infusion. Oral administration is generally preferred, however IV administration can be used if oral administration is not feasible or cannot be tolerated, or at the physician-investigator's clinical discretion. The dose will be adjusted to target a trough level of 200 to 300 ng/ml, which is in alignment with common clinical practice. The planned duration of CSA treatment is up to 14 days, with planned discontinuation upon discharge from the hospital. Dose reduction of 25% to 50% can be made for patients who experience adverse events such as hypertension or serum creatinine elevation.

The end of study will be study day 30 for those patients who have been discharged from the hospital. If the patient remains in the hospital, the subject will still complete the end of study visit at day 30 as planned, but will continue to be followed until date of discharge.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female, aged >18.
4. Admitted to hospital with laboratory confirmation of SARS-CoV-2 infection.
5. Estimated creatinine clearance >50 ml/min using standard Cockcroft-Gault formula.

Exclusion Criteria:

1. Are admitted to the ICU at time of enrollment.
2. Have an active uncontrolled infection with a non-COVID-19 agent.
3. Have an active malignancy, not including non-melanoma skin cancer, superficial cervical or bladder cancer, MGUS, or prostate cancer with PSA <1.0.
4. Are on chronic immune suppressive medications, including
5. corticosteroid therapy at a prednisone equivalent dose of 10 mg per day or higher; therapy with calcineurin inhibitors or mTOR inhibitors.
6. Are pregnant
7. Are lactating
8. Have a known allergic reaction to components of the CSA or its diluents.
9. Are receiving investigational vaccine for SARS-CoV-2.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm; Cyclosporine; oral or IV route of administration, per investigator discretion. Duration of administration up to 14 days, as tolerated.	Drug: Cyclosporine; • The initial dose will be 9 mg/kg/day oral divided q12h. For IV, the dose will be 3mg/kg/day by continuous IV infusion.; Other Names: Sandimmune, Neoral, Gengraf

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety-oxygen, ICU transfer and ventilation	Safety will be measured: By assessing the proportion of participants requiring increase in oxygen requirements, transfer to intensive care unit, and/or mechanical ventilation	3 months
Safety-changes in absolute lymphocyte count	Safety will be assessed: By monitoring changes in absolute lymphocyte counts	3 months
Safety-changes in creatinine clearance	Safety will be assessed: By monitoring changes in creatinine clearance. Creatinine clearance will be estimated using the Cockcroft-Gault formula.	3 months
Safety-secondary bacterial infections	Safety will be assessed: By monitoring the incidence of secondary bacterial infections complicating COVID-19 hospitalization	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Laboratory measurements of safety and antiviral efficacy related to COVID-19-SARS-CoV-2 by measuring the clearance of SARS-CoV-2 from respiratory secretions	To measure time to SARS-CoV-2 clearance (PCR negativity) at Days 7 and 14 by deep nasal swab	3 months
Laboratory measurements-D-dimer levels	To measure the laboratory correlatives of CRS/ Hemophagocytic lymphohistiocytosis (HLH) by measuring: D-dimer levels	3 months
Laboratory measurements-ferritin	To measure the laboratory correlatives of CRS/ Hemophagocytic lymphohistiocytosis (HLH) by measuring: ferritin levels	3 months
Laboratory measurements- IL-6	To measure the laboratory correlatives of CRS/ Hemophagocytic lymphohistiocytosis (HLH) by measuring: IL-6 levels	3 months

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Emily Blumberg, MD, University of Pennsylvania

Publications and helpful links

General Publications

• Blumberg EA, Noll JH, Tebas P, Fraietta JA, Frank I, Marshall A, Chew A, Veloso EA, Carulli A, Rogal W, Gaymon AL, Schmidt AH, Barnette T, Jurek R, Martins R, Hudson BM, Chavda K, Bailey CM, Church SE, Noorchashm H, Hwang WT, June CH, Hexner EO. A phase I trial of cyclosporine for hospitalized patients with COVID-19. JCI Insight. 2022 Jun 8;7(11):e155682. doi: 10.1172/jci.insight.155682.

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2020
• Primary Completion (Actual): October 25, 2021
• Study Completion (Actual): October 25, 2021

Study Registration Dates

• First Submitted: June 1, 2020
• First Submitted That Met QC Criteria: June 1, 2020
• First Posted (Actual): June 2, 2020

Study Record Updates

• Last Update Posted (Actual): January 11, 2022
• Last Update Submitted That Met QC Criteria: January 7, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 842998

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes