Clinical Trials Register

Summary
EudraCT Number:	2019-004109-28
Sponsor's Protocol Code Number:	DOLLARS
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:	2019-12-02
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

2019-004109-28

A.3

Full title of the trial

HIV-1 RNA decay in semen and rectum and changes in HIV reservoir in rectal tissue in ART-naïve HIV+ men treated with dolutegravir plus lamivudine compared to Bictegravir/FTC/TAF (“DOLLARS study”)

Disminución del RNA del VIH-1 en semen y recto, y cambios en el reservorio de VIH en tejido rectal en pacientes VIH+, naïve, hombres que inician tratamiento con dolutegravir y lamivudina comparado con Bictegravir/FTC/TAF (“Estudio DOLLARS”)

A.3.1

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

HIV virus decrease in semen and rectum in patients HIV+ men, who starts treatment with dolutegravir plus lamivudine compared to Bictegravir/FTC/TAF

Disminución del virus en semen y recto en pacientes hombres VIH+ que empiezan tratamiento con dolutegravir y lamivudina comparado con Bictegravir/FTC/TAF

A.4.1

Sponsor's protocol code number

DOLLARS

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	Daniel Podzamczer Palter
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	IDIBELL
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	Hospital Universitari de Bellvitge
B.5.2	Functional name of contact point	Unidad de VIH e ITS
B.5.3	Address:
B.5.3.1	Street Address	Feixa Llarga s/n
B.5.3.2	Town/ city	L'Hospitalet del Llobregat / Barcelona
B.5.3.3	Post code	08907
B.5.3.4	Country	Spain
B.5.4	Telephone number	+349326076672913
B.5.5	Fax number	+34932607669
B.5.6	E-mail	anavarroa@bellvitgehospital.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	TIVICAY
D.2.1.1.2	Name of the Marketing Authorisation holder	VIIV HEALTHCARE BV
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	DOLUTEGRAVIR SODIUM
D.3.9.1	CAS number	1051375-16-6
D.3.9.3	Other descriptive name	DOLUTEGRAVIR
D.3.9.4	EV Substance Code	SUB35122
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	50
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	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	Lamivudine (generic drug)
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	LAMIVUDINE
D.3.9.1	CAS number	134678-17-4
D.3.9.4	EV Substance Code	SUB08392MIG
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	300
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: 3
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.2.1.1.1	Trade name	Biktarvy
D.2.1.1.2	Name of the Marketing Authorisation holder	GILEAD SCIENCES IRELAND UC
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	BICTEGRAVIR SODIUM
D.3.9.1	CAS number	1611493-60-7
D.3.9.3	Other descriptive name	BICTEGRAVIR SODIUM
D.3.9.4	EV Substance Code	SUB188200
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	50
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EMTRICITABINE
D.3.9.1	CAS number	143491-57-0
D.3.9.4	EV Substance Code	SUB01882MIG
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	25
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TENOFOVIR ALAFENAMIDE FUMARATE
D.3.9.1	CAS number	1392275-56-7
D.3.9.3	Other descriptive name	TENOFOVIR ALAFENAMIDE FUMARATE
D.3.9.4	EV Substance Code	SUB178389
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	50
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

HIV infection

Infección por el VIH

E.1.1.1

Medical condition in easily understood language

HIV infection

Infección por el VIH

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

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 compare HIV-1 RNA decay kinetics in semen in ART-naïve HIV-1 infected male individuals treated with DTG/3TC dual therapy versus BIC/FTC/TAF.

Comparar la cinética de descomposición del ARN del VIH-1 en el semen en individuos varones infectados con VIH-1 sin tratamiento previo con ART tratados con terapia dual DTG / 3TC versus BIC / FTC / TAF.

E.2.2

Secondary objectives of the trial

To compare HIV-1 RNA decay kinetics in rectal fluid in ART-naïve HIV-1 infected male individuals treated with DTG/3TC dual therapy versus BIC/FTC/TAF.

Comparar la cinética de la descomposición del ARN del VIH-1 en el líquido rectal en individuos varones infectados con VIH-1 sin tratamiento previo con ART tratados con terapia dual DTG / 3TC versus BIC / FTC / TAF.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. HIV-1 infected male and female ≥ 18 years of age.
2. Not previously exposed to ART
3. Plasma viral load (HIV-1 RNA) at screening >1.000 copies/mL
4. Plasma viral load (HIV-1 RNA) <500,000 copies/mL and CD4+ T lymphocytes count at screening >200 cells/µL at screening
5. Signed and dated written informed consent prior to inclusion.

1. Hombres y mujeres infectados por el VIH ≥ 18 años de edad
2. No hayan tomado tratamiento antirretroviral previamente
3. Carga viral del VIH-1 RNA en plasma en la visita de screening > 1000 copias/mL
4. Carga viral del VIH-1 RNA en plasma en la viista de screening < 500,000 copias/mL y recuento de limfocitos >200 células/µL en la visita de screening
5. Obtención de consentimiento informado firmado y fechado previamente a la inclusión

E.4

Principal exclusion criteria

1. Plasma viral load (HIV-1 RNA) at screening >500,000 copies/mL
2. CD4+ T lymphocytes count at screening <200 cells/µL
3. Hepatitis B virus (HBV)
4. Severe hepatic impairment (Child-Pugh Class C)
5. Ongoing malignancy
6. Active opportunistic infection
7. Primary resistance to the study ARV drugs.
8. Ongoing therapy with any significant interaction with the study drugs.
9. Any verified Grade 4 laboratory abnormality
10. ALT or AST ≥ 3xULN and/or bilirubin ≥ 1.5xULN
11. Renal function impairment, defined as an estimated glomerular filtration rate < 50 mL/min
12. Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements.

1. Carga viral en plasma (HIV-1 RNA) en la visita de screening >500,000 copias/mL
2. Recuento de Linfocitos CD4+ al screening CD4+ T en la visita de screening <200 céls./µL
3. Infección por virus de la Hepatitis B (HBV)
4. Insuficiencia hepática severa (Child-Pugh Class C)
5. Neoplasia activa
6. Infección oportunista activa
7. Resistencias primarias al fármaco antiretroviral del estudio
8. Terapia activa que presente interacción significativa con los fármacos del estudio.
9. Algún valor de laboratorio verificado que suponga un Grado 4
10. ALT or AST ≥ 3xLSN y/or bilirubina ≥ 1.5xLSN
11. Insuficiencia renal, definida como un filtrado glomerular estimado < 50 mL/min
12. Cualquier otra condición clínica o tratamiento previo que, a criterio del investigador, pudiera hacer al sujeto inadecuado para el estudio o incapaz de cumplir con una correcta adherencia.

E.5 End points

E.5.1

Primary end point(s)

HIV-1 RNA decay in seminal plasma from baseline and up to 24 weeks after initiation of DTG/3TC vs Bictegravir/FTC/TAF.
HIV-1 RNA decay in rectal fluid from baseline and up to 24 weeks after initiation of DTG/3TC vs Bictegravir/FTC/TAF.

Disminución de la concentación del RNA del VIH-1 en plasma seminal desde la visita basal hasta 24 semanas de haber iniciado tratamiento.
Disminución de la concentación del RNA del VIH-1 en fluidos rectales desde la visita basal hasta 24 semanas de haber iniciado tratamiento.

E.5.1.1

Timepoint(s) of evaluation of this end point

24 weeks

24 semanas

E.5.2

Secondary end point(s)

HIV-1 RNA decay in blood plasma from baseline and up to 24 weeks after initiation of DTG/3TC vs Bictegravir/FTC/TAF.

Disminución de la concentación del RNA del VIH-1 en plasma sanguíneo desde la visita basal hasta 24 semanas de haber iniciado tratamiento.

E.5.2.1

Timepoint(s) of evaluation of this end point

24 weeks

24 semanas

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

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

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

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

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

1. Grade III or IV laboratory abnormalities or Adverse Events related to the study drug, or that in the investigator’s opinion, advise against continuing taking the study drugs.
2. Subject request to discontinue for any reason (withdrawal of consent).
3. Protocol non compliance.
4. Lost of follow up or death
5.Lack of treatment efficacy, defined as viral rebound in blood plasma after achieving viral suppression (VL<40 copies/mL) during the study period, confirmed by retest within 2 weeks.

1. Evento adverso o anomalías de laboratorio Grado II o IV relacionadas con el fármaco y que a críterio del investigador sean incompatibles con la continuidad del tratamiento
2. Retirada del consentimiento.
3. Incumplimiento del protocolo.
4. Pérdida de seguimiento o fallecimiento.
5. Falta de eficacia del tratamiento, definido como un rebote viral en plasma sanguíneo después de alcanzar la supresión viral durante el periódo de seguimiento del estudio, confirmado por retest a las dos semanas

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)

F.2 Gender

F.2.1

Female

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

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)

At the end of the study participants will offered to continue the same ART regimen, if it has not been withdrawn previously due to virological failure or toxicity. If the patient refuses to continue taking the same treatment, the best option for him will be provided by the study investigators, taking in to account patients’ characteristics and currently available drugs.

Al finalizar el estudio, se ofrecerá a los pacientes seguir con el mismo tratamiento, si no han abandonado previamente por toxicidad o fallo virológico. Si el paciente rechaza continuar con el mismo tratamiento, se le proporcionará la mejor opción por parte del equipo investigador, teniendo en cuenta las características del paciente y los fármacos disponibles en ese momento.

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

2020-01-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-01-15

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

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