Anti-Viral Effects of Voclosporin in COVID-19 Positive Kidney Transplant Recipients

NCT04701528 | Completed Phase 2

• 1 other identifier: NL73762.058.20
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

An open-label, 56 day, single-center, exploratory, proof-of-concept study of the anti-viral effect of voclosporin (VCS) with an extended safety follow-up, up to 1 year. Study population are adult KTRs with positive SARS-CoV-2 infection with mild to moderate symptoms. At study entry, subjects are on standard therapy of dual immunosuppressive treatment of prednisone and tacrolimus (TAC), following randomization, 10 out of 20 subjects will remain on this therapy for the duration of the study, while the other 10 subjects will switch to VCS.

Conditions

Covid19; Kidney Transplant Infection

Outcome Measures

Primary Outcomes (1)

• Time to viral clearance of SARS-CoV-2

  measured by first negative reverse transcription quantitative polymerase chain reaction (RT-qPCR) with a CT value of \>37 over 56 days

  Day 56

Secondary Outcomes (7)

• Time to 2 consecutive negative RT-qPCR tests with CT-value >37

  Day 56

• Time to reduction in viral load

  Day 56

• Time to 2 consecutive negative RT-qPCR tests with CT-value >24

  Day 56

• Time to clinical recovery

  Day 56

• Time to clinical symptom relief

  Day 56

Study Arms (2)

Voclosporin (VCS)

EXPERIMENTAL

Prior to or at study entry, subjects are reduced in their standard immunosuppressive therapy to dual therapy with prednisone and tacrolimus according to current local guidelines. In the experimental arm tacrolimus is switched to voclosporin 6 capsules (of 7.9 mg each) BID for a treatment period of minimal 56 days with a possible extension up to 1 year. Safety drug monitoring will take place during the study to ensure that VCS trough levels are maintained between 30-60 ng/mL. If trough levels are not within these levels, dose adjustments will take place.

Drug: Voclosporin

Tacrolimus (TAC)

ACTIVE COMPARATOR

Prior to or at study entry, subjects are reduced in their standard immunosuppressive therapy to dual therapy with prednisone and tacrolimus according to current local guidelines. In the Active comparator arm tacrolimus dosage is maintained. Safety drug monitoring will take place during the study to ensure that TAC trough levels are maintained between 3-7 ng/ml. If trough levels are not within these levels, dose adjustments will take place.

Drug: Tacrolimus

Interventions

Voclosporin DRUG

Temporarily switching of tacrolimus maintenance immunosuppression to voclosporin maintenance immunosuppression with possible additional anti-viral activity

Also known as: Specimen collection for Nuclear acid testing (NAT) on SARS-CoV-2

Voclosporin (VCS)

Tacrolimus DRUG

Comparator

Also known as: Specimen collection for Nuclear acid testing (NAT) on SARS-CoV-2

Tacrolimus (TAC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written informed consent.
• Male or female subjects with a minimum age of 18 years at Visit 1.
• Subjects with a stable kidney transplant taking TAC and a confirmed diagnosis of SARS-CoV-2 by nuclear acid testing, with mild-to-moderate symptoms.
• Patients with mild-to-moderate disease symptoms in which mild disease is defined by non-hospitalized patients without oxygen need and moderate disease symptoms are defined by hospitalization to a nursing ward with the need of oxygen therapy.
• Women of childbearing potential must have a negative pregnancy test at baseline. Two effective forms of contraception must be used simultaneously unless abstinence is the chosen method. Subjects must use effective contraception during the study.

You may not qualify if:

• Subjects unable or unwilling to give written informed consent and/or to comply with study procedures.
• Any known hypersensitivity or contraindication to CNIs, especially CsA, or components of any cyclosporine drug product.
• Current or medical history of:
• Congenital immunodeficiency.
• Severe, known, active viral infections, excluding SARS-CoV-2, within 3 months of baseline (e.g., cytomegalovirus, hepatitis B virus, hepatitis C virus or HIV) that are deemed to interfere with study assessments or outcome according to Investigator's judgement.
• Severe symptoms resulting from SARS-CoV-2 infection defined by requiring admittance to a medium or high care unit with the need for positive pressure ventilation at baseline.
• Other major physical or psychiatric illness or major traumatic injury or any other medical condition associated with increased risk to the subject or that may affect study conduct or interfere with study assessments or outcome according to Investigator's judgement.
• Subjects who are pregnant, breast feeding or, if of childbearing potential, not using adequate contraceptive precautions.
• Participation in another interventional clinical study within 4 weeks prior to baseline and/or receipt of investigational drugs within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to baseline.
• Subjects less than 3 months post-transplant.
• Subjects with documented organ rejection within the past 3 months.
• Subjects with a documented estimated glomerular filtration rate (eGFR) \<15 ml/min within the previous 3 months prior to screening.

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Aurinia Pharmaceuticals Inc.: collaborator

Study Sites (1)

Leiden University Medical Center

Leiden, 2333 ZC, Netherlands

Location

MeSH Terms

Conditions

COVID-19

Interventions

voclosporin; Specimen Handling; N-acetyltalosaminuronic acid; Tacrolimus

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Macrolides; Lactones; Organic Chemicals

Study Officials

• Y.K.O. Teng, MD, PhD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Y.K.O. Teng, MD, PhD

Model Details: single-center, proof-of-concept

Study Record Dates

• First Submitted: October 27, 2020
• First Posted: January 8, 2021
• Study Start: November 15, 2020
• Primary Completion: March 25, 2022
• Study Completion: October 25, 2022
• Last Updated: October 17, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)