Clinical Trials Register

Summary
EudraCT Number:	2020-005162-33
Sponsor's Protocol Code Number:	RF-2018-12365308
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2023-08-21
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-005162-33

A.3

Full title of the trial

Targeting inflammation in depression using minocycline: a patient stratification approach using peripheral inflammatory biomarkers, PET and MRI

Trattamento dell’infiammazione con Minociclina in pazienti depressi: utilizzo di un approccio stratificato mediante infiammazione periferica, PET e MRI

A.3.1

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

Treatment of inflammation with Minocycline in depressed patients

Trattamento dell’infiammazione con Minociclina in pazienti depressi

A.3.2

Name or abbreviated title of the trial where available

RF-2018-12365308

A.4.1

Sponsor's protocol code number

RF-2018-12365308

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	IRCCS CENTRO SAN GIOVANNI DI DIO - FATEBENEFRATELLI AFFERENTE ALLA PROVINCIA LOMBARDO VENETA ORDINE OSPEDALIERO DI SAN G
B.1.3.4	Country	Italy
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	Ministero della Salute
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli
B.5.2	Functional name of contact point	Servizio Clinical Trial
B.5.3	Address:
B.5.3.1	Street Address	Via Pilastroni 4
B.5.3.2	Town/ city	Brescia
B.5.3.3	Post code	25125
B.5.3.4	Country	Italy
B.5.4	Telephone number	0303501503
B.5.6	E-mail	sct.irrcs@fatebenefratelli.eu

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	No
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.3.1	Product name	(R)-[N-metil-11C]PK11195
D.3.2	Product code	[(R)-N-metil-11CPK11195]
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	205934-46-9
D.3.9.2	Current sponsor code	n/a
D.3.9.3	Other descriptive name	N-sec-butil-1-(2-clorofenil)-N-[11C]metilisochinolin-3-carbossiammide
D.3.10	Strength
D.3.10.1	Concentration unit	Sv sievert
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Yes
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.IMP: 2
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	Minocin
D.2.1.1.2	Name of the Marketing Authorisation holder	Teofarma Srl
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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.3.1	Product name	Minocic
D.3.2	Product code	[n/a]
D.3.4	Pharmaceutical form	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.3.9.1	CAS number	10118-90-8
D.3.9.2	Current sponsor code	MInociclina
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	200
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)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Yes
D.3.11.13.1	Other medicinal product type	antibiotico per uso sistemico

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

depressed patients with high levels of inflammation (crp>2 mg/l) and non responder to at least two different antidepressants

depressione maggiore con alti livelli infiammatori (crp>2 mg/l) e non responder a due farmaci antidepressivi differenti

E.1.1.1

Medical condition in easily understood language

depressed patients with high levels of inflammation and non responder to at least two different antidepressants

pazienti depressi che presentano alti livelli di infiammazione e non rispondono a due trattamenti antidepressivi diversi

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10057840
E.1.2	Term	Major depression
E.1.2	System Organ Class	10037175 - Psychiatric disorders

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 evaluate an improvement in the inflammatory state after 8 weeks of treatment with a minocycline in addition to the current antidepressant treatment

valutare un miglioramento dello stato infiammatorio a livello periferico dopo 8 settimane di trattamento con Minociclina in aggiunta al trattamento antidepressivo in corso

E.2.2

Secondary objectives of the trial

1. To evaluate an improvement of the depressive symptoms after 8 weeks of treatment with a minocycline in addition to the current antidepressant treatment;
2. To evaluate changes in central inflammation levels (microglia activation) after 8 weeks of treatment with a minocycline in addition to the current antidepressant treatment;
3.To evaluate possible brain changes at structural and functional level with MRI after 8 weeks of treatment with a minocycline in addition to the current antidepressant treatment;
4. To evaluate possible correlations between observed changes with MRI, microglia activation, peripheral inflammation and improvement of the depressive symptoms

1. Valutare un miglioramento dei sintomi depressivi dopo 8 settimane di trattamento con Minociclina in aggiunta al trattamento antidepressivo in corso;
2. Valutare cambiamenti nei livelli di infiammazione centrale (attivazione microglia) dopo 8 settimane di trattamento con Minociclina in aggiunta al trattamento antidepressivo in corso
3. Valutare possibili cambiamenti cerebrali a livello strutturale e funzionale mediante MRI dopo 8 settimane di trattamento con Minociclina in aggiunta al trattamento antidepressivo in corso;
4. Valutare possibili correlazioni tra cambiamenti osservati con MRI, attivazione della microglia, infiammazione periferica e miglioramento dei sintomi depressivi.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• presence of major non psychotic depression according to DSM - 5
• crp> 2;
• do not respond to two antidepressants;
• accept minocycline
• no contraindications to minocycline
• no contraindications to 11C PK PET

• Presenza di depressione maggiore non psicotica secondo DSM – 5;
• PCR (proteina c reattiva)>2;
• Non responder a due antidepressivi;
• Accettare l’introduzione di Minociclina
• Assenza di controindicazioni a ricevere trattamento con Minociclina;
• Assenza di controindicazioni a sottoporsi alla 11C PK PET.

E.4

Principal exclusion criteria

• drug sensitivity
• acute inflammation or autoimmune pathology;
• pregnancy or breastfeeding;
• suicidal thoughts
• hscrp>20 mg/l;
• having been exposed to radiotracers within the 7 previous days

• Sensibilita’ a minococlina e storia di grave allergia o ipersensibilità verso i farmaci;
• Infiammazione acuta o patologia autoimmune;
• Livelli di hscrp>20 mg/l;
• Essere stati sottoposti a imaging o a procedure basate su utilizzo di radiofarmaci nei 7 giorni precedenti la sessione di imaging di questo studio;
• Gravidanza e allattamento;
• Pensieri suicidi.

E.5 End points

E.5.1

Primary end point(s)

improvement of depressive symptomatology

miglioramento della sintomatologia depressiva

E.5.1.1

Timepoint(s) of evaluation of this end point

8 weeks

otto settimane

E.5.2

Secondary end point(s)

demonstrate the clinical efficacy of the minocycline in depressed patients not responding stratified on the basis of the inflammation levels

dimostrare l’efficacia clinica della Minociclina in pazienti depressi non responder, stratificati in base ai livelli di infiammazione

E.5.2.1

Timepoint(s) of evaluation of this end point

8 weeks

8 settimane

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

E.6.4

Safety

E.6.5

Efficacy

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

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

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

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

the conclusion of the research will coincide with the conclusion of the eight weeks of treatment of the last patient

la conclusione della sperimentazione coinciderà con la conclusione delle otto settimane di trattamento dell’ultimo paziente.

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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:

F.1.3

Elderly (>=65 years)

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

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2023-08-21.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

in the month following the end of the treatment with minocycline, a researcher will contact the patient to confirm and integrate what emerged during the monitoring of the trial

nel mese successivo al termine del trattamento con Minociclina, un ricercatore si occuperà di contattare telefonicamente i pazienti per confermare quanto emerso dal monitoraggio della sperimentazione.

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

2022-08-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-11-08

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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