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ALTERNATION Trial: A Clinical Trial Evaluating Everolimus-Based, Calcineurin Inhibitor-Free Immunosuppression One Year After Liver Transplantation
EU CTIS ID: 2025-524312-11-00
What this study is testing
The primary objective is to demonstrate that Calcineurin-inhibitor (CNI)-free immunosuppression (IS) is superior in sparing kidney function (measured as change from baseline to 14 months in estimated glomerular filtration rate (eGFR)) beyond year one after liver transplantation compared to standard therapy with CNI-based IS regimen in liver allograft recipients without relevant subclinical graft injury.
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 1. Men**, women* (biological sex), aged ≥ 18 or <80 years; *Women without childbearing potential defined as follows: • at least 6 weeks after surgical sterilization by salpingectomy or bilateral oophorectomy or • hysterectomy or uterine agenesis or • ≥ 50 years and in postmenopausal state > 1 year or • < 50 years and in postmenopausal state > 1 year with serum FSH > 40 IU/l and serum estrogen < 30 ng/l or a negative estrogen test, both at screening or *Women of childbearing potential: • Must have a negative pregnancy test at screening with a sensitivity of at least 25 mIU/ml. A repeat negative pregnancy test is required immediately prior to treatment initiation at baseline to confirm non-pregnancy status. • Must agree to undergo additional pregnancy testing as specified in section 6.2, or when clinically indicated (e.g., following a reported contraceptive failure). • Must agree to use at least one highly effective method of contraception (as defined in section 3.2.1) from the time of screening until 8 weeks after completion of studytreatment. • For participants using hormonal contraception, a barrier method (preferably a male condom) must be used in addition to the primary method from screening until 8 weeks after the end of treatment, to minimize the risk of reduced contraceptive efficacy **Sexually active and fertile male study subjects • Must use a condom from screening, during treatment with mycophenolate mofetil (MMF) and for at least 90 days after discontinuation of treatment. • If the male participant has a female partner of childbearing potential who is not pregnant, additional contraceptive measures should be considered for the partner. • The requirement for condom use may be waived provided that a highly effective method of contraception is consistently used by the female partner of childbearing potential.
- 2. Signed written informed consent from subject
- 3. Liver allograft recipients, either deceased or living donor liver transplant
- 4. Liver transplantation more than 12 months ago and less than 36 months ago
- 5. Recipients of single organ transplant only
- 6. Liver Transplant Recipient (LTR) on CNI-based maintenance IS
You likely can't join if
- 1. Previous CNI-free IS
- 5. Need for chronic anti-coagulation that cannot be safely discontinued to perform a liver biopsy
- 6. Inability to participate in frequent monitoring of liver function (every 8 weeks) and clinical visits during the trial duration (38 months)
- 7. Malignancy or active infection including active, replicative viral hepatitis (chronic hepatitis does not belong to exclusion criteria)
- 8. Recurrence of underlying liver disease
- 9. Subjects who are pregnant or breastfeeding
See the full eligibility criteria
Who can join
- 1. Men**, women* (biological sex), aged ≥ 18 or <80 years; *Women without childbearing potential defined as follows: • at least 6 weeks after surgical sterilization by salpingectomy or bilateral oophorectomy or • hysterectomy or uterine agenesis or • ≥ 50 years and in postmenopausal state > 1 year or • < 50 years and in postmenopausal state > 1 year with serum FSH > 40 IU/l and serum estrogen < 30 ng/l or a negative estrogen test, both at screening or *Women of childbearing potential: • Must have a negative pregnancy test at screening with a sensitivity of at least 25 mIU/ml. A repeat negative pregnancy test is required immediately prior to treatment initiation at baseline to confirm non-pregnancy status. • Must agree to undergo additional pregnancy testing as specified in section 6.2, or when clinically indicated (e.g., following a reported contraceptive failure). • Must agree to use at least one highly effective method of contraception (as defined in section 3.2.1) from the time of screening until 8 weeks after completion of studytreatment. • For participants using hormonal contraception, a barrier method (preferably a male condom) must be used in addition to the primary method from screening until 8 weeks after the end of treatment, to minimize the risk of reduced contraceptive efficacy **Sexually active and fertile male study subjects • Must use a condom from screening, during treatment with mycophenolate mofetil (MMF) and for at least 90 days after discontinuation of treatment. • If the male participant has a female partner of childbearing potential who is not pregnant, additional contraceptive measures should be considered for the partner. • The requirement for condom use may be waived provided that a highly effective method of contraception is consistently used by the female partner of childbearing potential.
- 2. Signed written informed consent from subject
- 3. Liver allograft recipients, either deceased or living donor liver transplant
- 4. Liver transplantation more than 12 months ago and less than 36 months ago
- 5. Recipients of single organ transplant only
- 6. Liver Transplant Recipient (LTR) on CNI-based maintenance IS
- 7. Liver enzymes: alanine aminotransferase (ALT) < 2x upper limit of normal (ULN) and ALP < 2xULN
What rules you out
- 1. Previous CNI-free IS
- 5. Need for chronic anti-coagulation that cannot be safely discontinued to perform a liver biopsy
- 6. Inability to participate in frequent monitoring of liver function (every 8 weeks) and clinical visits during the trial duration (38 months)
- 7. Malignancy or active infection including active, replicative viral hepatitis (chronic hepatitis does not belong to exclusion criteria)
- 8. Recurrence of underlying liver disease
- 9. Subjects who are pregnant or breastfeeding
- 15. The use of any prohibited medication specified in section 5.2 is not permitted, unless the patient can be safely transitioned to an alternative medication at least 5 half-lives prior to the start of study-specific treatment (baseline).
- 10. Hypersensitivity or intolerance to any of the components of the medications used
- 11. Participation in another clinical trial (other investigational drugs or devices at the time of enrolment or within 30 days prior enrolment or within five half-lives of the IMP, whichever is longer)
- 12. Any medical condition which could compromise participation in the study according to the investigator’s assessment.
- 13. Accommodation in an institution pursuant to a court or administrative order
- 14. Histological exclusion criteria in the baseline screening biopsy: a. more than mild portal tract inflammation, presence of interface hepatitis, more than mild lobular inflammation b. presence of biliary inflammation, endothelialitis, portal microvasculitis, central perivenulitis c. advanced fibrosis (≥2 in any scale of LAF score) d. evidence of acute or chronic rejection (T cellmediated or antibody-mediated, plasma-cell-rich, chronic ductopenic rejection)
- 2. Acute or chronic rejection within the 36 months prior to screening
- 3. Prednisolone intake due to another autoimmune disease for no longer than 8 weeks
- 4. eGFR <30ml/min and/or proteinuria >0.5g/l (to mitigate the risk of worsening renal failure should rejection occur and high level of CNI might be required and proteinuria as a contraindication for mTORI-based therapy)
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.