Cyclosporine in Patients With Moderate COVID-19

• ClinicalTrials.gov Identifier: NCT04412785
• Recruitment Status: Completed
• First Posted: June 2, 2020
• Last Update Posted: January 11, 2022
• Sponsor: University of Pennsylvania
• Information provided by (Responsible Party): University of Pennsylvania

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Cyclosporine	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Trial for the Prevention of Cytokine Release Syndrome (CRS) With Cyclosporine in Patients With Moderate COVID-19
• Actual Study Start Date: June 30, 2020
• Actual Primary Completion Date: October 25, 2021
• Actual Study Completion Date: October 25, 2021

Arms and Interventions

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 Name: Sandimmune, Neoral, Gengraf

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. 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 [ Time Frame: 3 months ]
   To measure time to SARS-CoV-2 clearance (PCR negativity) at Days 7 and 14 by deep nasal swab
2. Laboratory measurements-D-dimer levels [ Time Frame: 3 months ]
   To measure the laboratory correlatives of CRS/ Hemophagocytic lymphohistiocytosis (HLH) by measuring: D-dimer levels
3. Laboratory measurements-ferritin [ Time Frame: 3 months ]
   To measure the laboratory correlatives of CRS/ Hemophagocytic lymphohistiocytosis (HLH) by measuring: ferritin levels
4. Laboratory measurements- IL-6 [ Time Frame: 3 months ]
   To measure the laboratory correlatives of CRS/ Hemophagocytic lymphohistiocytosis (HLH) by measuring: IL-6 levels

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

University of Pennsylvania

Investigators

• Principal Investigator: Emily Blumberg, MD; University of Pennsylvania

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT04412785
• Other Study ID Numbers: 842998
• First Posted: June 2, 2020
• Last Update Posted: January 11, 2022
• Last Verified: January 2022

• 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

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Cyclosporine; Cyclosporins; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antifungal Agents; Anti-Infective Agents; Dermatologic Agents; Antirheumatic Agents; Calcineurin Inhibitors