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Summary
EudraCT Number:	2019-000134-18
Sponsor's Protocol Code Number:	RenoMet
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-02-13
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

A. Protocol Information

A.1

Member State Concerned

Belgium - FPS Health-DGM

A.2

EudraCT number

2019-000134-18

A.3

Full title of the trial

Metformin as RenoProtector in Non-Diabetic Patients with Progressive Chronic Kidney Disease (CKD stages 2, 3A and 3B): a multi-centre, practice-oriented, repurposing, double-blind, placebo-controlled, randomized clinical trial.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Metformin as RenoProtector of Progressive Kidney Disease

A.3.2

Name or abbreviated title of the trial where available

RenoMet

A.4.1

Sponsor's protocol code number

RenoMet

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	University of Antwerp
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Belgian Health Care Knowledge Centre (KCE)
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University of Antwerp
B.5.2	Functional name of contact point	Prof. Dr. Marc De Broe
B.5.3	Address:
B.5.3.1	Street Address	Universiteitsplein 1
B.5.3.2	Town/ city	Wilrijk
B.5.3.3	Post code	2610
B.5.3.4	Country	Belgium
B.5.6	E-mail	Marc.Debroe@uantwerpen.be

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Glucophage SR 500mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck n.v./s.a.
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Prolonged-release tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	METFORMIN
D.3.9.1	CAS number	657-24-9
D.3.9.4	EV Substance Code	SUB08831MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic Kidney Disease (CKD stage 2, 3A, 3B)

E.1.1.1

Medical condition in easily understood language

Chronic Kidney Disease (CKD stage 2, 3A, 3B)

E.1.1.2

Therapeutic area

Diseases [C] - Symptoms and general pathology [C23]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To demonstrate that a Metformin dose of 1000 mg/day, can effectively and safely slow the progression of renal failure in non-diabetic patients with chronic renal failure stages CKD 2, CKD3A and 3B

E.2.2

Secondary objectives of the trial

To show that chronic renal failure patients treated with Metformin compared to patients treated with placebo will have (1) lower mortality, (2) slower decrease of their renal function, (3) less development of end-stage renal disease, (4) less co-morbidity, (5) lower hospitalization rate, (6) improved quality of life, (7) limited adverse drug reactions

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients will be eligible for inclusion in the RenoMet study based on the following inclusion criteria:
- Adult patients (18-75 years) of both gender
- Seen on a regular base in one of the participating outpatient clinics of renal care with a previous consultation within the last year
- Having a chronic kidney disease with:
- A CKD stage 2, 3A or 3B ( i.e. with estimated glomerular filtration rate (eGFR) between 30 and 90 ml/min/1.73m2) at the time of the baseline visit
- Without proteinuria or with proteinuria below or equal to 2 g/24hrs
- Showing a decline of eGFR between 2.0 and 15.0 ml/min/year determined using at least three determinations of eGFR (CKD-Epi formula) within the last three years before inclusion.

E.4

Principal exclusion criteria

Patients will be excluded from study participation based on the following exclusion criteria:
1. Illiteracy: patients not knowing how to read or write
2. Patients not able to communicate in Dutch or French
3. Patients with mental deterioration, incapable to give informed consent and to understand the safety instructions of the study (at the discretion of the treating nephrologist)
4. Patients with one of the following clinical problems:
- Patients with overt proteinuria (more than 2 g/24hrs)
- Patients showing a fast decline of renal function (more than 15 ml/min/year) during the preceding three years
- Diabetes mellitus (any type: 1, 2, maturity onset diabetes of the young (MODY)…) confirmed by a glycemia level > 126 mg/L (7.0 mmol/L) after a fasting time of 8 hours
- Chronic obstructive pulmonary disease ( COPD) stage Gold IV (Oxygene-dependency)
- Congestive heart failure (NYHA stage IV)
- Inflammatory bowel disease (IBD)
- Stoma
- Hepatic insufficiency or cirrhosis, acute alcohol intoxication or alcoholism (> 20 glasses of alcoholic beverages per week)
- History of solid organ transplantation
- History of metabolic diseases (e.g. mitochondrial encephalomyopathy (MELAS), lactic acidosis, stroke-like episodes, etc…)
- Pregnancy and/or lactating women at the time of recruitment and during the study period
5. Patient with one of the following medication:
- Prior use of metformin within the past 12 months (e.g. glucose intolerance, polycystic ovary syndrome, etc…)
- Chronic use of CNI (calcineurine inhibitors) (e.g. psoriasis...)
6. Patients showing elevated serum lactate level(s) at the time of recruitment ( i.e. a serum lactate level >2.5 mmol/L at baseline visit or a confirmed serum lactate level > 2.0 mmol/L within a period of 4 weeks)
7. Hypersensitivity to metformin or to any of the excipients listed in section 6.1 of the Glucophage SR SmPC (see Attachment A5 Glucophage SR SmPC)
8. One of the following diseases during the previous 6 months: myocardial infarction, shock, acute problems of decompensated heart failure or respiratory failure.

E.5 End points

E.5.1

Primary end point(s)

Time to event of reaching a 30% decline of eGFR over the investigation period of 30 months in the intervention group compared to the control group, expressed as a hazard ratio in a time-to-event analysis.

E.5.1.1

Timepoint(s) of evaluation of this end point

Period of 30 months

E.5.2

Secondary end point(s)

•Incidence of mortality, development of end-stage renal disease, specific co-morbidities and hospitalization
•Evolution of the renal function
•Quality of life
•Adverse drug reactions

E.5.2.1

Timepoint(s) of evaluation of this end point

Period of 30 months

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

For an individual patient, the trial will end at the date that the patient has his last follow-up visit (FU visit 8, i.e. 30 months after trial initiation). This visit will be at the same time the End-of-Study visit (EoS), except for patients with an ongoing SAE at that time. They will have an extra visit and their EoS one month later.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

289

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

385

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-03-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-08-26

P. End of Trial
P.	End of Trial Status	Ongoing

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