COVID-19Phase 1NCT04412785
Cyclosporine in Patients With Moderate COVID-19
A Phase 1 study testing Cyclosporine in people with COVID-19, run by University of Pennsylvania at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Cyclosporine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Jun 2020to 25 Oct 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged >18.
- Admitted to hospital with laboratory confirmation of SARS-CoV-2 infection.
- Estimated creatinine clearance >50 ml/min using standard Cockcroft-Gault formula.
Who cannot join
- Are admitted to the ICU at time of enrollment.
- Have an active uncontrolled infection with a non-COVID-19 agent.
- Have an active malignancy, not including non-melanoma skin cancer, superficial cervical or bladder cancer, MGUS, or prostate cancer with PSA <1.0.
- Are on chronic immune suppressive medications, including
- corticosteroid therapy at a prednisone equivalent dose of 10 mg per day or higher; therapy with calcineurin inhibitors or mTOR inhibitors.
- Are pregnant
Show all 9Show fewer
- Are lactating
- Have a known allergic reaction to components of the CSA or its diluents.
- Are receiving investigational vaccine for SARS-CoV-2.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: 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.
Read the 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.
- Conditions
- COVID-19
- Being tested
- Cyclosporine
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclosporineDrug
Also called Sandimmune, Neoral, Gengraf
- 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.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | Cyclosporine; oral or IV route of administration, per investigator discretion. Duration of administration up to 14 days, as tolerated. Receives: Drug: Cyclosporine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 3 months
Safety-changes in absolute lymphocyte count
Safety will be assessed: By monitoring changes in absolute lymphocyte counts
Measured: 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.
Measured: 3 months
Safety-secondary bacterial infections
Safety will be assessed: By monitoring the incidence of secondary bacterial infections complicating COVID-19 hospitalization
Measured: 3 months
Secondary outcomes (4)
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
Measured: 3 months
Laboratory measurements-D-dimer levels
To measure the laboratory correlatives of CRS/ Hemophagocytic lymphohistiocytosis (HLH) by measuring: D-dimer levels
Measured: 3 months
Laboratory measurements-ferritin
To measure the laboratory correlatives of CRS/ Hemophagocytic lymphohistiocytosis (HLH) by measuring: ferritin levels
Measured: 3 months
Laboratory measurements- IL-6
To measure the laboratory correlatives of CRS/ Hemophagocytic lymphohistiocytosis (HLH) by measuring: IL-6 levels
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2020
- Study start30 Jun 2020
- Primary completion25 Oct 2021
- Study completion25 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Emily Blumberg, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04412785
- Sponsor's protocol ID
- 842998
- Status last verified
- Jan 2022
- First submitted
- 1 Jun 2020
- Last updated
- 11 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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.
PubMed 35536669
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial for the Prevention of Cytokine Release Syndrome (CRS) With Cyclosporine in Patients With Moderate COVID-19
- ClinicalTrials.gov ID
- NCT04412785
- Acronym / sponsor ID
- 842998
- Conditions
- COVID-19
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 30 Jun 2020 (actual)
- Primary completion
- 25 Oct 2021 (actual)
- Study completion
- 25 Oct 2021 (actual)
- First posted
- 2 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: CyclosporineCyclosporine; oral or IV route of administration, per investigator discretion. Duration of administration up to 14 days, as tolerated. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged >18.
- Admitted to hospital with laboratory confirmation of SARS-CoV-2 infection.
- Estimated creatinine clearance >50 ml/min using standard Cockcroft-Gault formula.
Key exclusion criteria (9 listed)
- Are admitted to the ICU at time of enrollment.
- Have an active uncontrolled infection with a non-COVID-19 agent.
- Have an active malignancy, not including non-melanoma skin cancer, superficial cervical or bladder cancer, MGUS, or prostate cancer with PSA <1.0.
- Are on chronic immune suppressive medications, including
- corticosteroid therapy at a prednisone equivalent dose of 10 mg per day or higher; therapy with calcineurin inhibitors or mTOR inhibitors.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CyclosporineAlso: Sandimmune, Neoral, Gengraf• 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. | Drug | Single Arm |
Primary outcome
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
Safety-changes in absolute lymphocyte count
Time frame: 3 months
Safety will be assessed: By monitoring changes in absolute lymphocyte counts
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.
Safety-secondary bacterial infections
Time frame: 3 months
Safety will be assessed: By monitoring the incidence of secondary bacterial infections complicating COVID-19 hospitalization
4 secondary outcomes
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
Laboratory measurements-D-dimer levels
Time frame: 3 months
Laboratory measurements-ferritin
Time frame: 3 months
Laboratory measurements- IL-6
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2022.
- Derived from this study: PubMed 35536669Blumberg 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emily Blumberg, MD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cyclosporine in people with COVID-19, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety-oxygen, ICU transfer and ventilation (time frame: 3 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04412785, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2022.