Introduction of mTor Inhibitors and the Activation of the Cytomegalovirus (CMV) -Specific Cellular Immune Response

NCT04936971 | Withdrawn Phase 4

• 1 other identifier: ACTIVA
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Kidney transplant patients under an immunosuppressive treatment based on anti-calcineurin and mycophenolate-mofetil and induction therapy with rATG who suffer from early systemic viral replication by the CMV virus could benefit from the introduction of an i-mTor drug. (everolimus) to replace mycophenolate mofetil. This conversion would be effective in slowing down and controlling viral expansion without the need to initiate any prophylactic anti-viral therapy thanks to the activation of the CMV-specific cellular effector response or to an antiviral effect of i-Mtor itself.

Conditions

Kidney Transplantation; Cytomegalovirus Infections

Keywords

Cytomegalovirus; kidney transplant; ELISPOT

Outcome Measures

Primary Outcomes (1)

• Proportion of patients who require initiation of anti-viral treatment with valganciclovir

  Proportion of patients who require initiation of anti-viral treatment with valganciclovir after reaching a viral replication threshold greater than 5000IU / ml evaluated in plasma being asymptomatic, comparing the different arms

  3 months

Secondary Outcomes (11)

• Incidence of CMV disease

  3 months

• Recurrence of CMV infection after initiation of anti-viral treatment

  3 months

• Recurrence of CMV infection after switch to everolimus treatment

  3 months

• Kinetic of the CMV-specific cellular response

  3 months

• Titration of anti-CMV antibodies in serum

  3 months

Study Arms (2)

Everolimus

EXPERIMENTAL

Kidney transplant induction with Rabbit Anti-Thymocyte globulin (rATG) as per local practice. Kidney transplant manteinance treatment with Tacrolimus (TAC) to achieve 4-6 ng/mL trough levels, Everolimus (EVL) to achieve 3-8 ng/mL trough levels and Corticosteroids (CS) as per local practice.

Other: no intervention

Mycophenolate Mofetil

ACTIVE COMPARATOR

Kidney transplant induction with Rabbit Anti-Thymocyte globulin (rATG) as per local practice. Kidney transplant manteinance treatment with Tacrolimus (TAC) to achieve 4-6 ng/mL trough levels, Mycofenolate Mofetil (MMF) 500mg/bid and Corticosteroids (CS) as per local practice.

Drug: Switch from Mycophenolate Mofetil to Everolimus manteinance treatment in Active Comparator Arm

Interventions

Switch from Mycophenolate Mofetil to Everolimus manteinance treatment in Active Comparator Arm DRUG

Switch from Mycophenolate Mofetil in Active comparator Arm if assymptomatic Cytomegalovirus viremia \>1000-\<5000 copies/mL observed

Also known as: Switch to Certican

Mycophenolate Mofetil

no intervention OTHER

Manteinance of assigned Arm treatment even if assymptomatic Cytomegalovirus viremia \>1000-\<5000 copies/mL observed

Everolimus

Eligibility Criteria

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

You may qualify if:

• Subjects must be 18 years or older (and weigh more than 34Kg) and may be of both sexes and of any race.
• Subjects will be seropositive for CMV virus and will receive a seropositive graft (CMV IgG D + / R +).
• Subjects must be willing and able to give their written informed consent to the trial. If a subject cannot independently grant their informed consent in writing, her legal representative may do so in her place.
• Women of childbearing potential (WOCBP) must perform a pregnancy test at the time of enrollment and agree to the use of a medically acceptable contraceptive method during the selection period and while receiving the medication specified in the protocol. A woman of childbearing age is considered to be any woman physiologically capable of becoming pregnant, from menarche to becoming postmenopausal, unless she is permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menstruation for 12 months without an alternative medical cause. A high level of follicle stimulating hormone (FSH) in the postmenopausal range can be used to confirm a postmenopausal state in women not using hormonal contraceptives or hormone replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
• Only women of childbearing age who adhere to the contraceptive methods recommended by the Clinical Trial Facilitation Group (CTFG) as highly effective contraceptive methods may participate, that is, with a failure rate of less than 1% per year when used consistently and correct:
• Combined hormonal contraception (containing estrogen and progestin) associated with inhibition of ovulation (oral, intravaginal or transdermal).
• Progestin-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable)
• Intrauterine device (IUD)
• Intrauterine Hormone Release System (IUS)
• Bilateral tubal occlusion
• Vasectomized partner (provided the partner is the participant's only sexual partner in the WOCBP trial and the vasectomized partner has received a medical evaluation of surgical success)
• Sexual abstinence (defined as abstaining from sexual intercourse for the entire risk period associated with study treatments)
• Patients without a medical contraindication for the use of i-mTOR.
• Immunosuppressive induction rATG.

You may not qualify if:

• Subjects may not have a history of type I hypersensitivity or idiosyncratic reactions to drugs ganciclovir (GCV) or valganciclovir (VGCV).
• Pregnant women.
• Breastfeeding women.
• Subjects may not have any clinically significant disease that could interfere with study evaluations.
• Participation in another clinical trial promoted by the pharmaceutical industry, in which the promoter already establishes in the protocol what the treatment of CMV should be.
• Patients with active viral replication of the HCV, HBV and / or HIV viruses.
• Patients requiring a desensitizing treatment that includes plasma exchange, Campath-1, Rituximab®, Eculizumab® and / or Gammaglobulin.
• Presence of donor-specific antibodies (DSA).
• Prior intolerance to study medication (Certican®), prior documented history of hereditary galactose intolerance, Lapp's lactase deficiency, or glucose or galactose malabsorption.

Sponsors & Collaborators

• Edoardo Melilli: lead

Study Sites (1)

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

MeSH Terms

Conditions

Cytomegalovirus Infections

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Model Details: Prospective, open label, randomized, two arms, paralel, compared to Standard of Care treatment

Study Record Dates

• First Submitted: June 16, 2021
• First Posted: June 23, 2021
• Study Start: September 1, 2021
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2021
• Last Updated: February 28, 2024

Record last verified: 2021-06

Locations

ES (1)