Clinical Trials Register

Summary
EudraCT Number:	2017-003470-14
Sponsor's Protocol Code Number:	FIMHCSVIH-2017
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:	2018-09-17
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

2017-003470-14

A.3

Full title of the trial

Pilot clinical trial, multicenter, to compare the efficacy of RTG 1200 QD vs DRV-cb (800-150) QD both in combination with TAF/FTC in patients with HIV and CD4 infection <200 cells/microL.

Ensayo clínico piloto, multicéntrico, para comparar la eficacia de RTG 1200 QD vs DRV-cb (800-150) QD ambos en combinación con TAF/FTC en pacientes con infección VIH y CD4<200 cél/microL

A.3.1

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

Raltegravir One Thousand two hundred vs Darunavir-cb in Immnunosupressed Patients: ROTDIP Study

Raltegravir 1200 versus Darunavir-cb en pacientes inmunodeprimidos: estudio ROTDIP

A.3.2

Name or abbreviated title of the trial where available

ROTDIP Study

Estudio ROTDIP

A.4.1

Sponsor's protocol code number

FIMHCSVIH-2017

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	FIMABIS Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
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 Merck Sharp & Dohme
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	FIMABIS
B.5.2	Functional name of contact point	Plataforma de Estudios Clinicos
B.5.3	Address:
B.5.3.1	Street Address	Hospital Regional Universitario Pabellon A. Planta 7. Avda. Carlos Haya s/n
B.5.3.2	Town/ city	Málaga
B.5.3.3	Post code	29010
B.5.3.4	Country	Spain
B.5.4	Telephone number	34951291447
B.5.6	E-mail	estudios.clinicos@fimabis.org
B.Sponsor: 2
B.1.1	Name of Sponsor	APES Costa del Sol (Agencia Pública Empresarial Sanitaria Costa del Sol)
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 MErck Sharp & Dohme
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	APES Costa del Sol (Agencia Pública Empresarial Sanitaria Costa del Sol)
B.5.2	Functional name of contact point	Coordinación y Gestión Ensayos Clín
B.5.3	Address:
B.5.3.1	Street Address	Autovía A-7, Km 187
B.5.3.2	Town/ city	Marbella
B.5.3.3	Post code	29603
B.5.3.4	Country	Spain
B.5.4	Telephone number	34951976620
B.5.6	E-mail	gestionensayos.ephcs@hcs.es

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	ISENTRESS
D.2.1.1.2	Name of the Marketing Authorisation holder	MSD Merck Sharp & Dohme
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	Film-coated 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	RALTEGRAVIR
D.3.9.1	CAS number	518048-05-0
D.3.9.3	Other descriptive name	RAL
D.3.9.4	EV Substance Code	SUB25667
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	600
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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.2.1.2	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
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	DARUNAVIR
D.3.9.1	CAS number	206361-99-1
D.3.9.4	EV Substance Code	SUB25394
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	800
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	COBICISTAT
D.3.9.1	CAS number	1004316-88-4
D.3.9.4	EV Substance Code	SUB33760
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	150
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) infection

Infección por el Virus de Inmunodeficiencia Humana (VIH)

E.1.1.1

Medical condition in easily understood language

Human Immunodeficiency Virus (HIV) infection

Infección por el 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	LLT
E.1.2	Classification code	10020442
E.1.2	Term	Human immunodeficiency virus status
E.1.2	System Organ Class	100000004848

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 explore the efficacy of RAL 1200 mg QD versus DRV/Cb 800-150 mg QD, both in
combination with TAF/FTC in subjects infected with HIV naive with a CD4 count <200 cells/μL.

Explorar la eficacia de RAL 1200 mg QD frente a DRV/cb 800-150 mg QD, ambos en
combinación con TAF/FTC en sujetos infectados por el VIH naive con recuento de CD4<200 células/μL.

E.2.2

Secondary objectives of the trial

- Explore differences in tolerability, immunological recovery, persistence and results reported by the patient between both regimens:
1. Compare the proportion of patients in virological failure after 48 weeks.
2. Compare the proportion of patients who interrupt the treatment for any reason after 48 weeks.
3. Analyze the percentage change in the number of CD4 lymphocytes at week 48 .
4. Compare the proportion of patients with CD4> 200 cells/μL at week 48.
5. Evaluate at week 48 the percentage of change in total cholesterol, LDL and HDL cholesterol, triglycerides, CT/HDL ratio and cardiovascular risk predictive value after 10 years (Framingham).
6. Check the modification of the FG (CKD-EPI).

- Explorar las diferencias de tolerabilidad, recuperación inmunológica, persistencia y resultados informados por el paciente entre ambos regímenes:
1. Comparar la proporción de pacientes en fallo virológico a 48 semanas.
2. Comparar la proporción de pacientes que interrumpen el tratamiento por cualquier causa a 48 semanas.
3. Analizar el cambio porcentual de la cifra de linfocitos CD4 a 48 semanas.
4. Comparar la proporción de pacientes con CD4>200 cél/μL a 48 semanas.
5. Evaluar a las 48 semanas el porcentaje de cambio en colesterol total, colesterol LDL y HDL, triglicéridos, ratio CT/HDL y el valor predictivo de RCV a 10 años (Framingham).
6. Comprobar la modificación del FG (CKD-EPI).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Subject ≥ 18 years of age.
- HIV-1 infection.
- Naive to antiretroviral treatment.
- CD4 count at the beginning of the study <200 cells/μl.
- Estimated glomerular filtration ≥ 50 mL/min, according to the formula CKD-EPI.
- Grant Informed Consent in writing to participate in the study.

- Sujetos ≥ 18 años de edad.
- Infección por el VIH-1.
- Naive al tratamiento antirretroviral.
- Recuento de CD4 al inicio del estudio <200 células/μl.
- Filtrado glomerular estimado≥ 50 mL/min, de acuerdo con la fórmula CKD-EPI.
- Otorgan su Consentimiento Informado por escrito para participar en el estudio.

E.4

Principal exclusion criteria

- Lactating, pregnant or fertile women who do not commit to maintain contraceptive measures during the trial.
- Concomitant use of any drug with possible pharmacological interaction with the study drugs that it is advisable to "avoid" through the database for interactions at the University of Liverpool (www.hiv-druginteractions.org).
- Previous use of any antiretroviral for HIV infection.
- Resistance to the study drugs, or presence of any contraindication to use it. The inclusion in the study can be carried out before receiving the result of the resistance test. Once it is received, in case of presenting any mutation of resistance to drugs of the indicated regimen, the responsible clinical investigator will decide whether to withdraw or maintain the original treatment and, therefore, whether to withdraw or keep the patient in the study, also being able to decide whether to censure said patient in the efficacy analysis. In any case, if the patient is not removed from the trial, he will remain in the safety analysis.
- Therapies that include interferon, interleukin-2, cytotoxic chemotherapy or immunosuppressants at the entrance to the study.
- Current consumption of alcohol or other substances that at the discretion of the investigator may interfere with the compliance of the subject study.
- Subjects who currently participate in any other clinical trial using a research product, with the exception of studies in which the treatment studied has been stopped for more than 12 weeks.
- AIDS event in diagnosis of HIV infection or in the 3 months prior to the inclusion of the study.
- Suspected severe hepatopathy (grades B or C of the Child-Pough classification), of any origin, according to the clinician.
- Any other clinical condition or previous treatment that, in the investigator's judgment, makes the subject unsuitable for the study or unable to comply with the dosage requirements.

- Mujeres lactantes, embarazadas o fértiles que no se comprometan a mantener medidas contraceptivas durante el ensayo.
- Uso concomitante de cualquier fármaco con posible interacción farmacológica con los fármacos del estudio que sea recomendable “evitar” por la base de datos para interacciones de la Universidad de Liverpool (www.hiv-druginteractions.org ).
- Uso previo de cualquier antirretroviral para la infección por el VIH.
- Resistencia a los medicamentos del estudio, o presencia de cualquier contraindicación para usarla. La inclusión en el estudio se puede llevar a cabo antes de recibir el resultado del test de resistencias. Una vez que se recibe el mismo, en caso de presentar alguna mutación de resistencia a fármacos del régimen indicado, el investigador clínico responsable decidirá si retirar o mantener el tratamiento original y, por lo tanto, si retirar o mantener al paciente en el estudio, pudiendo además decidir si censurar a dicho paciente en el análisis de eficacia. En todo caso, si el paciente no es retirado del ensayo permanecerá en el análisis de seguridad.
- Terapias que incluyen interferón, interleucina-2, quimioterapia citotóxica o inmunosupresores en la entrada al estudio.
- Consumo actual de alcohol o de otras sustancias que a criterio del investigador pueda interferir con el cumplimiento del estudio sujeto.
- Los sujetos que actualmente participan en cualquier otro ensayo clínico utilizando un producto de investigación, con la excepción de los estudios en los que el tratamiento estudiado se ha detenido durante más de 12 semanas.
- Evento SIDA en diagnóstico de infección por el VIH o en los 3 meses anteriores a la inclusión del estudio.
- Sospecha de hepatopatía severa (grados B o C de la clasificación de Child-Pough), de cualquier origen, a juicio del clínico.
- Cualquier otra condición clínica o tratamiento previo que, a juicio del investigador, haga al sujeto inadecuado para el estudio o que no pueda cumplir con los requisitos de dosificación.

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients with viral load of HIV-1 <50 cop / mL 48 weeks after initiation of ART (snapshot analysis).

Proporción de pacientes con carga viral de VIH-1<50 cop/mL a las 48 semanas de haber iniciado TAR (análisis por snapshot).

E.5.1.1

Timepoint(s) of evaluation of this end point

At week 48

A las 48 semanas

E.5.2

Secondary end point(s)

- Proportion of patients in virological failure at 48 weeks.
- Proportion of patients who interrupt the treatment for any reason at 48 weeks.
- Percentage change in the number of CD4 lymphocytes at 48 weeks.
- Proportion of patients with CD4> 200 cells / μL at 48 weeks.
- Percentage change in total cholesterol, LDL and HDL cholesterol, triglycerides, CT/HDL ratio and RCV at 10 years (Framingham)
- Modification of the FG (CKD-EPI)

- Proporción de pacientes en fallo virológico a 48 semanas.
- Proporción de pacientes que interrumpen el tratamiento por cualquier causa a 48 semanas.
- Cambio porcentual de la cifra de linfocitos CD4 a 48 semanas.
- Proporción de pacientes con CD4>200 cél/μL a 48 semanas.
- Porcentaje de cambio en colesterol total, colesterol LDL y HDL, triglicéridos, ratio CT/HDL y RCV a 10 años (Framingham)
- Modificación del FG (CKD-EPI)

E.5.2.1

Timepoint(s) of evaluation of this end point

At week 48

En la semana 48

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

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

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

Yes

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

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

Última visita del último paciente

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)

Those patients who finish or withdraw from the trial, will receive the best available treatment. Withdrawal will not derive in liability or harm, affect their subsequent medical treatment or the relationship with the professionals who are treating them.

Aquellos pacientes que finalicen o se retiren del ensayo, recibirán el mejor tratamiento disponible, sin que su retirada derive en responsabilidad ni perjuicio alguno, afecte a su tratamiento médico posterior o a la relación con los profesionales que le están tratando.

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

2018-12-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-11-13

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

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