Clinical Trials Register

Summary
EudraCT Number:	2022-001591-33
Sponsor's Protocol Code Number:	DoRSwitch.21
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2022-07-27
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

2022-001591-33

A.3

Full title of the trial

Open-label, single-arm, unicenter and Pilot Study of a Switch strategy from Etravirine (ETR) to Doravirine (DOR) in Virologically-Suppressed HIV-1 Infected Adults With ETR-Resistance

Estudio abierto, de un solo brazo, unicéntrico y piloto de una estrategia de cambio de etravirina (ETR) a doravirina (DOR) en adultos infectados por VIH-1 virológicamente suprimidos con resistencia a ETR

A.3.1

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

Pilot Study of a Switch strategy from Etravirine (ETR) to Doravirine (DOR) in Virologically-Suppressed HIV-1 Infected Adults With ETR-Resistance

Estudio piloto de una estrategia de cambio de etravirina (ETR) a doravirina (DOR) en adultos infectados por VIH-1 virológicamente suprimidos con resistencia a ETR

A.4.1

Sponsor's protocol code number

DoRSwitch.21

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 Clinic 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	MSD
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CTU clínic
B.5.2	Functional name of contact point	Anna Cruceta
B.5.3	Address:
B.5.3.1	Street Address	Carrer Mallorca 183
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08036
B.5.3.4	Country	Spain
B.5.6	E-mail	acruceta@recerca.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	PIFELTRO
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme B.V.
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	Capsule
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	Doravirine
D.3.9.1	CAS number	1338225-97-0
D.3.9.4	EV Substance Code	SUB177834
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	100
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

Human Immunodeficiency Virus (HIV)

Virus de Inmunodeficiencia Humana (VIH)

E.1.1.1

Medical condition in easily understood language

Human Immunodeficiency Virus (HIV)

Virus de Inmunodeficiencia Humana (VIH)

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10020161
E.1.2	Term	HIV infection
E.1.2	System Organ Class	10021881 - Infections and infestations

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 assess the efficacy of a switch of Etravirine (ETR) to Doravirine (DOR) for maintenance of virologic suppression at 48 weeks (<50 copies/mL) on HIV infected patients

Evaluar la eficacia de un cambio de etravirina (ETR) a doravirina (DOR) para el mantenimiento de la supresión virológica a las 48 semanas (<50 copias/ml) en pacientes infectados por el VIH.

E.2.2

Secondary objectives of the trial

1. To evaluate the HIV viral load of participants at week 12, 24 and 48.
2. Evaluating the immune effects of the treatment switch from ETR to DOR.
3. To assess safety and tolerability of switching Etravirine for Doravirine.
4. To study the pharmacokinetic interaction between DRV/r and DRV/c with DOR in a substudy of 5 individuals.

1. Evaluar la carga viral del VIH de los participantes en las semanas 12, 24 y 48.
2. Evaluación de los efectos inmunes del tratamiento cambio de ETR a DOR.
3. Evaluar la seguridad y la tolerancia del cambio de Etravirina por Doravirina.
4. Estudiar la interacción farmacocinética entre DRV/r y DRV/c con DOR en un subestudio en el que participarán 5 pacientes.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

pharmacokinetic interaction between DRV/r (darunavir/ritonavir) and DRV/c(darunavir/cobicistat) with DOR (Doravirine)

interacción farmacocinética entre DRV/r (darunavir/ritonavir) y DRV/c (darunavir/cobicistat) con DOR (Doravirina)

E.3

Principal inclusion criteria

• HIV-1-infected subjects with age ≥18 years old.
• Desire of the patient to simplify their ART-regimen.
• Having plasma HIV-1 RNA < 50 copies/mL during at least the previous 24 weeks.
• Currently receiving an ETR-containing regimen (unchanged during the previous 24 weeks).
• Documented pooled/historical genotype or GRT in pro-viral DNA must show the presence of 103N and/or 181C and/or 190A and/or 100I and/or 138K/A.

• Sujetos infectados por el VIH-1 con edad ≥18 años de edad.
• Deseo del paciente de simplificar su régimen de TAR
• Tener ARN plasmático VIH-1 < 50 copias/ml durante al menos las 24 semanas anteriores
• Actualmente recibiendo un régimen que contiene ETR (sin cambios durante las 24 semanas anteriores).
• El genotipo o GRT documentado agrupado/histórico en el ADN pro-viral debe mostrar la presencia de 103N y/o 181C y/o 190A y/o 100I y/o 138K/A.

E.4

Principal exclusion criteria

• Documented pooled/historical genotype or GRT in pro-viral DNA of any DOR-DRM (Mutations V106A, Y188L, and M230L, and combinations of V106A and L234I; V106A and F227L and L234I; and V106A and 190A and F227L).
• Pregnant, breastfeeding women, women with a positive pregnancy test at the time of screening, sexually active fertile women wishing to conceive or unwilling to commit to contraceptive methods, for the duration of the study and until 4 weeks after the last dose of study medication. All women are considered fertile unless they have undergone a sterilizing surgery or are over the age of 50 with spontaneous amenorrhea for over 12 months prior to study entry.
• Active tuberculosis infection.
• Any clinical condition or therapy that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with the dosing requirements.

• Genotipo agrupado/histórico documentado o GRT en ADN pro-viral de cualquier DOR-DRM (Mutaciones V106A, Y188L y M230L, y combinaciones de V106A y L234I; V106A y F227L y L234I; y V106A y 190A y F227L)
• Mujeres embarazadas, lactantes, mujeres con una prueba de embarazo positiva en el momento de la detección, mujeres fértiles sexualmente activas que deseen concebir o no estén dispuestas a comprometerse con métodos anticonceptivos (consulte el Apéndice 1 para la lista aceptada de los métodos altamente efectivos para evitar el embarazo), durante la duración del estudio y hasta 4 semanas después de la última dosis de medicamento del estudio. Todas las mujeres se consideran fértiles a menos que se hayan sometido a una cirugía esterilizante o sean mayores de 50 años con amenorrea espontánea durante más de 12 meses antes del ingreso al estudio.
• Infección tuberculosa activa.
• Cualquier condición clínica o terapia que, en opinión del investigador, haría que el individuo no sea adecuado para el estudio o no pueda cumplir con los requisitos de dosificación.

E.5 End points

E.5.1

Primary end point(s)

Percentage of participants with confirmed VL>50 copies/mL

Porcentaje de participantes con CV>50 copias confirmadas/ml

E.5.1.1

Timepoint(s) of evaluation of this end point

week 24

semana 24

E.5.2

Secondary end point(s)

1. Percentage of participants with VL>50 copies/mL and VL<50 copies/mL
2. Changes in CD4, CD8 cell counts and ratio CD4/CD8
3. To assess safety and tolerability, measured by the number de AEs and SAEs related with the treatment
4. To determine the pharmacokinetic interaction between DRV/r and DRV/c with DOR at weeks 2 and 4

1. Porcentaje de participantes con CV>50 copias/ml y CV<50 copias/ml
2. Cambios en CD4, recuento de células CD8 y relación CD4/CD8
3. Evaluar la seguridad y la tolerancia, lo cual se medirá por el número de AEs y SAEs relacionados con el tratamiento
4. Determinar la interacción farmacocinética entre DRV/r y DRV/c con DOR

E.5.2.1

Timepoint(s) of evaluation of this end point

1. at week 12, 24 and 48
2. at 48 weeks
3. at 48 weeks
4. at weeks 2 and 4

1. en las semanas 12,24 y 48
2. a las 48 semanas
3. a las 48 semanas
4. en las semanas 2 y 4

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

Yes

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

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

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.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

Last visit of the last subject

Última visita del último sujeto

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:

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

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)

The patient can continue with the treatment if he wishes to

El paciente puede continuar con el tratamiento si lo desea

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

2022-10-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-10-04

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2023-07-27

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