Clinical Trials Register

Summary
EudraCT Number:	2018-002465-18
Sponsor's Protocol Code Number:	PROTEDI
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-08-09
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

Spain - AEMPS

A.2

EudraCT number

2018-002465-18

A.3

Full title of the trial

Efficacy and tolerance of 4 weeks of tedizolid in prosthetic joint infections treated with implant removal

Eficacia y tolerancia de 4 semanas de tedizolid en infecciones articulares protésicas tratadas previamente con recambio del implante

A.3.1

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

Efficacy and tolerance of 4 weeks of tedizolid in prosthetic joint infections treated with implant removal

Eficacia y tolerancia de 4 semanas de tedizolid en infecciones articulares protésicas tratadas previamente con recambio del implante

A.3.2

Name or abbreviated title of the trial where available

PROTEDI

A.4.1

Sponsor's protocol code number

PROTEDI

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	Fundació Clínic per a la Recerca Biomèdica
B.1.3.4	Country	Spain
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	Bristol-Myers Squid
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	Clinical Trials Unit (CTU)
B.5.2	Functional name of contact point	Anna Cruceta
B.5.3	Address:
B.5.3.1	Street Address	Calle Rosselló 138
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08036
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034932279838
B.5.6	E-mail	acruceta@clinic.cat

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	SIVEXTRO
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme de España, S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	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	TEDIZOLID
D.3.9.1	CAS number	856867-55-5
D.3.9.2	Current sponsor code	MK-1986
D.3.9.3	Other descriptive name	TEDIZOLID PHOSPHATE
D.3.9.4	EV Substance Code	SUB35385
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)	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

prosthetic joint infections treated with implant removal.

infecciones de prótesis articulares tratadas con recambio de implante.

E.1.1.1

Medical condition in easily understood language

Prosthetic joint infections treated with implant removal.

Infecciones de prótesis articulares tratadas con recambio de implante.

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

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 evaluate the efficacy of 4 weeks of 200 mg/24h of tedizolid for prosthetic join infections caused by tedizolid susceptible microorganisms treated with implant removal in one or two stages at 6 months of follow-up after stopping tedizolid treatment.

evaluar la eficacia de 4 semanas de 200 mg / 24 h de tedizolid para las infecciones protéiscas causadas por microorganismos susceptibles a tedizolid tratadas previamente con recambio del implante en una o dos etapas a los 6 meses de seguimiento después de suspender el tratamiento con tedizolid.

E.2.2

Secondary objectives of the trial

- Evaluate the efficacy of tedizolid at 12 months of follow-up
- evaluate the rate of gastrointestinal adverse events with tedizolid
- determine the rate of haematological abnormalities during tedizolid treatment
- in case of two-stage exchange, the rate of positive cultures during reimplantation.

- Evaluar la eficacia de tedizolid a los 12 meses de seguimiento;
- evaluar la tasa de eventos adversos gastrointestinales con tedizolid;
- determinar la tasa de anormalidades hematológicas durante el tratamiento con tedizolid
- en caso de intercambio en dos etapas, la tasa de cultivos positivos durante el reimplante.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female older than 18 years who accept and sign the informed consent.
2. Infection signs onset more than 3 months after index arthroplasty.
3. Diagnostic of chronic (≥3 weeks of clinical symptoms) hip or knee prosthetic joint infection according to MSIS criteria *(Parvizi J, Gherke T. Definition of peri-prosthetic joint infection. J Arthroplasty 2014; 29: 1331)
4. Infection due to a tedizolid susceptible microorganism.
5. Surgical approach: one or two – stage exchange of all implant components.
6. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

1. Hombres o mujeres mayores de 18 años que acepten y firmen el consentimiento informado.
2. Inicio de los signos de infección más de 3 meses después de la artroplastia índice.
3. Diagnóstico de infecciones crónicas (≥3 semanas de síntomas clínicos) de artroplastia de cadera o rodilla según los criterios del MSIS * (Parvizi J, Gherke T. Definición de infección articular peri-protésica, J Arthroplasty 2014; 29: 1331)
4. Infección debido a un microorganismo sensible a tedizolid.
5. Enfoque quirúrgico: intercambio de una o dos etapas de todos los componentes del implante.
6. Dispuesto y capaz de cumplir con las visitas programadas, el plan de tratamiento, las pruebas de laboratorio y otros procedimientos de estudio.

E.4

Principal exclusion criteria

1. Patients with a prosthetic joint infection with negative cultures.
2. Patients who undergo debridement without removing the prosthesis or only partially removed
3. ≥15 days of other antibiotic treatment before starting tedizolid
4. Life expeancy ≤ 1 year.
5. Previous enrollment in this protocol.
6. Hypersensitivity to tedizolid or any formulation excipients.
7. Concurrent use of another investigational medication within 30 days of study entry.
8. Women who are pregnant or breast-feeding

1. Pacientes con una infección articular protésica con cultivos negativos.
2. Pacientes que se someten a desbridamiento sin extirpar la prótesis o solo parcialmente extirpada.
3. ≥15 días de otro tratamiento con antibióticos antes de comenzar el tedizolid.
4. Esperanza de vida ≤ 1 año.
5. Inscripción previa en este protocolo.
6. Hipersensibilidad a tedizolid o cualquier excipiente de formulación.
7. Uso concurrente de otro medicamento en investigación dentro de los 30 días posteriores al ingreso al estudio.
8. Mujeres que están embarazadas o amamantando.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint will be the investigator-assessed clinical outcome (surgical wound closed and absence of local signs of infection) at the 9th visit (6 months after finishing tedizolid treatment).

El punto final primario será el resultado clínico evaluado por el investigador (herida quirúrgica cerrada y ausencia de signos locales de infección) en la novena visita (6 meses después de terminar el tratamiento con tedizolid).

E.5.1.1

Timepoint(s) of evaluation of this end point

The 9th visit (6 months after finishing tedizolid treatment).

La novena visita (6 meses después de finalizar el tratamiento con tedizolid).

E.5.2

Secondary end point(s)

Secondary Efficacy endpoints:
1. Investigator-assessed clinical outcomes (surgical wound closed and absence of local signs of infection) at the 10th visit (12 months after finishing tedizolid treatment).
2. The rate of positive cultures during reimplantation on the two stage exchange cases.

Safety endpoints:
3. The rate of gastrointestinal adverse events notified during the follow-up time (from the 3th until de 10th and last visit).
4. The rate of hematological abnormalities (anemia,thrombocytopenia and leucopenia) evidenced by laboratory values during the treatment (3rd, 4th, 5th and 6th visits).

Los endpoints de eficacia secundarios:
1. Resultados clínicos evaluados por el investigador (herida quirúrgica cerrada y ausencia de signos locales de infección) en la 10ª visita (12 meses después de finalizar el tratamiento con tedizolid).
2. La tasa de cultivos positivos durante el reimplante en los casos de intercambio de dos etapas.

Endpoints secundarios de seguridad:
3. La tasa de eventos adversos gastrointestinales notificados durante el tiempo de seguimiento (del 3 al 10 y última visita).
4. La tasa de anomalías hematológicas (anemia, trombocitopenia y leucopenia) evidenciadas por valores de laboratorio durante el tratamiento (3ª, 4ª, 5ª y 6ª visitas).

E.5.2.1

Timepoint(s) of evaluation of this end point

1. The 10th visit (12 months after finishing tedizolid treatment).
2. during reimplantation
3. during the follow-up time (from the 3th until de 10th and last visit).
4. during the treatment (3rd, 4th, 5th and 6th visits).

1. La 10a visita (12 meses después de terminar el tratamiento con tedizolid).
2. durante el reimplante
3. durante el tiempo de seguimiento (del 3 al 10 y última visita).
4. durante el tratamiento (3ª, 4ª, 5ª y 6ª visitas).

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

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

E.8.1.2

Open

Yes

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

Yes

E.8.1.7.1

Other trial design description

un grupo

one group

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

Yes

E.8.2.3.1

Comparator description

cohortes historicas

historical cohorts

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

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

LVLS

ÚLTIMO PACIENTE ÚLTIMA VISITA

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.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

Yes

F.3.3.1

Women of childbearing potential not using contraception

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.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

Ninguna

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-12-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-12-12

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

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