ElucidatiNg Immunosuppressant pharmacokinetic variabilities by investigating Gut Microbiota modulations After kidney transplantation - ENIGMA

2023-508335-31-00 Protocol ENIGMA Therapeutic use (Phase IV) Ongoing, recruiting

Start 2 Sep 2024 · Status Ongoing, recruiting · 1 EU/EEA countries · 1 sites · Protocol ENIGMA

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Ongoing, recruiting
Participants planned 50
Countries 1
Sites 1

Chronic renal failure

The primary aim of our clinical study is to identify staging biomarkers of immunosuppressant (mainly Tacrolimus and mycophenolate mofetil) pharmacokinetic variability by investigating the gut microbiota modulations and physiological changes after kidney transplantation.

Key facts

Sponsor
Universite Catholique de Louvain
Participant type
Patients
Age range
18-64 years
Gender
Male and Female
Therapeutic area
Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]
Trial duration
2 Sep 2024 → ongoing
Decision date (initial)
2024-03-18
Transition trial
No
Low-intervention
Yes
Rare-disease indication
No
Vulnerable population
No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Pharmacokinetic, Pharmacodynamic

The primary aim of our clinical study is to identify staging biomarkers of immunosuppressant (mainly Tacrolimus and mycophenolate mofetil) pharmacokinetic variability by investigating the gut microbiota modulations and physiological changes after kidney transplantation.

Conditions and MedDRA coding

Chronic renal failure

VersionLevelCodeTermSystem organ class
21.1 LLT 10077912 Renal retransplantation 10042613
21.1 LLT 10009119 Chronic renal failure 10038359

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

  1. (i) diagnosis of chronic renal failure
  2. (ii) planned for a kidney transplantation from a living-donor kidney
  3. (iii) followed at Cliniques universitaires Saint-Luc
  4. (iv) immunosuppressive treatment includes a combination of Tacrolimus (Advagraft) and mycophenolate mofetil (Cellcept)
  5. (v) aged between 18 and 75 years old at time of inclusion.
  6. (vi) BMI ranging from 18 to 35 kg/m2
  7. (viii) not being pregnant
  8. (viiii) able to speak and to understand French

Exclusion criteria 6

  1. (i) diagnosis of inflammatory bowel disease (IBD)
  2. (ii) having undergone or planed for bariatric surgery
  3. (iii) alcohol or drug addiction
  4. (iv) BMI lower than 18 or > than 35 kg/m2
  5. (v) not able to provide informed consent
  6. (vi) pregnancy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Immunosuppressive drug pharmacokinetic parameters, including tacrolimus, mycophenolic acid (the active moiety of mycophenolate mofetil) and glucuronides (MPA-glucuronide and acyl-MPA-glucuronide). Microbiota composition and function. Antibiotic pharmacokinetics

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Tacrolimus Monohydrate

SUB23141 · Substance

Active substance
Tacrolimus Monohydrate
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL
Max daily dose
0.20 mg/kg milligram(s)/kilogram
Max total dose
0.30 mg/kg milligram(s)/kilogram
Max treatment duration
5200 Week(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Mycophenolate Mofetil

SUB03360MIG · Substance

Active substance
Mycophenolate Mofetil
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL
Max daily dose
2 g gram(s)
Max total dose
2 g gram(s)
Max treatment duration
5200 Week(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Tacrolimus Monohydrate

SUB23141 · Substance

Active substance
Tacrolimus Monohydrate
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL
Max daily dose
0.20 mg/kg milligram(s)/kilogram
Max total dose
0.30 mg/kg milligram(s)/kilogram
Max treatment duration
5200 Week(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Tacrolimus Monohydrate

SUB23141 · Substance

Active substance
Tacrolimus Monohydrate
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL
Max daily dose
0.20 mg/kg milligram(s)/kilogram
Max total dose
030 mg/kg milligram(s)/kilogram
Max treatment duration
5200 Week(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universite Catholique de Louvain

Sponsor organisation
Universite Catholique de Louvain
Address
Place De L'Universite 1
City
Ottignies-Louvain-La-Neuve
Postcode
1348
Country
Belgium

Scientific contact point

Organisation
Universite Catholique de Louvain
Contact name
Laure Elens

Public contact point

Organisation
Universite Catholique de Louvain
Contact name
Laure Elens

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Belgium Ongoing, recruiting 50 1
Rest of world 0

Investigational sites

Belgium

1 site · Ongoing, recruiting
Cliniques Universitaires Saint-Luc
nephrology, Hippokrateslaan 10, Batiment 54, Sint-Lambrechts-Woluwe

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Belgium 2024-09-02 2024-09-04

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1-Protocol_2023-508335-31-00_public with track changes 4
Protocol (for publication) D1-Protocol_2023-508335-31-00_public_clean 4
Protocol (for publication) D10_instructions blood collection VAMS 1
Protocol (for publication) D11_FFQ_V1 1
Protocol (for publication) D4_Patient facing document_drug diary 1
Protocol (for publication) D4_Patient facing document_food diary 1
Protocol (for publication) D5_Monitoring plan_2023-508335-31-00_public 1
Protocol (for publication) D6_Data management plan_2023-508335-31-00_public 1
Protocol (for publication) D7_Patient flyer 1
Protocol (for publication) D8_Storyboard video ENIGMA 1
Protocol (for publication) D9_Storyboard video VAMS 1
Recruitment arrangements (for publication) Recruitment arrangements 1
Subject information and informed consent form (for publication) L1_ICF receiver V4_clean 4
Summary of Product Characteristics (SmPC) (for publication) G1_SmPC_advagraf 1
Summary of Product Characteristics (SmPC) (for publication) G1_SmPC_advagraf 1
Summary of Product Characteristics (SmPC) (for publication) G1_SmPC_advagraf 1
Summary of Product Characteristics (SmPC) (for publication) G1_SmPC_cellcept 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_BE FR NL GER_2023-508335-31-00 1

Application history

3 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2023-11-27 Belgium Acceptable with conditions
2024-03-11
2024-03-18
2 SUBSTANTIAL MODIFICATION SM-1 2024-04-11 Belgium Acceptable
2024-05-24
2024-05-24
3 SUBSTANTIAL MODIFICATION SM-3 2025-09-08 Belgium Acceptable
2025-10-23
2025-10-27