Clinical Trials Register

Summary
EudraCT Number:	2016-000087-42
Sponsor's Protocol Code Number:	TAISTR_2016
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:	2019-04-11
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

2016-000087-42

A.3

Full title of the trial

A prospective, single arm, open-label 96 week observational trial of the tolerability, adherence and efficacy of a dolutegravir/abacavir/lamivudine single tablet regimen in HIV-1 antibody positive people living with HIV with a history of injection drug use switching from existing ART or starting treatment after discontinuation of ART

Estudio multicéntrico, prospectivo, rama única, abierto, observacional durante 96 semanas para evaluar la tolerabilidad, adherencia y eficacia de un régimen antirretroviral basado en un único comprimido de dolutegravir / abacavir / lamivudina en personas VIH- positivas con historia de uso de drogas inyectables que son naïve para el TAR, cambian de un régimen previo o empiezan tratamiento después de haber discontinuado TAR.

A.3.1

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

Triumeq As an Integrase Single Tablet Regimen in People with HIV who Inject Drugs

Triumeq como parte de un régimen basado en comprimido único en personas con VIH que usan drogas inyectables

A.3.2

Name or abbreviated title of the trial where available

TAISTR

A.4.1

Sponsor's protocol code number

TAISTR_2016

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	University College Dublin
B.1.3.4	Country	Ireland
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	ViiV Healthcare
B.4.2	Country	Ireland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University College Dublin
B.5.2	Functional name of contact point	HIV Molecular Research Group
B.5.3	Address:
B.5.3.1	Street Address	Catherine McAuley Education and Research Centre, 21 Nelson Street
B.5.3.2	Town/ city	Dublin
B.5.3.3	Post code	Dublin 7
B.5.3.4	Country	Ireland
B.5.4	Telephone number	+35317164538
B.5.5	Fax number	+35317164539
B.5.6	E-mail	hivmrg@ucd.ie

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	Triumeq
D.2.1.1.2	Name of the Marketing Authorisation holder	ViiV Healthcare UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Triumeq
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	Dolutegravir (as sodium salt)
D.3.9.1	CAS number	1051375-16-6
D.3.9.2	Current sponsor code	GSK1349572A
D.3.9.3	Other descriptive name	DOLUTEGRAVIR SODIUM
D.3.9.4	EV Substance Code	SUB130591
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	Abacavir (as sulfate)
D.3.9.1	CAS number	188062-50-2
D.3.9.2	Current sponsor code	GI265235 (1592U89 Hemisulfate)
D.3.9.3	Other descriptive name	ABACAVIR SULFATE
D.3.9.4	EV Substance Code	SUB00231MIG
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.3.8 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.3.9.2	Current sponsor code	GR109714X
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.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

HIV infection

Infección por VIH

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

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 assess the tolerability, adherence and efficacy of single tablet dolutegravir/abacavir/lamivudine antiretroviral therapy in people living with HIV with a history of injection drug use who are either ART-naïve or switching from existing ART or starting treatment after discontinuation of ART

Evaluar la tolerabilidad, adherencia y eficacia de un régimen antirretroviral basado en un único comprimido de dolutegravir/abacavir/lamivudina en personas VIH- positivas con historia de uso de drogas inyectables que son naïve para el TAR, cambian de un régimen previo o empiezan tratamiento después de haber discontinuado TAR.

E.2.2

Secondary objectives of the trial

-To determine change in number and severity of reported ART-related adverse effects
-To determine change in health-related quality of life (HRQOL)
-To determine change in frailty score
-To determine the percentage of subject with unscheduled ART discontinuations/interruptions
-To determine the estimated number of weeks of missed ART
-To determine change of medication possession ratio (MPR) or adherence score
-To determine the percentage of subjects with HIV RNA<40 copies/mL
-To determine change in genotypic resistance profiles in subjects experiencing virological failure
-To determine change in CD4+ T-cell counts
-To determine change in bone mineral density
-To determine the number of subjects with any adverse and any serious adverse events (SAE)
-To determine the number of subject with Grade 1 to 4 laboratory abnormalities

-Determinar el cambio en el número y la gravedad de los efectos adversos relacionados con el TAR.
-Determinar el cambio en la calidad de vida relacionada con la salud (HRQOL)
-Determinar el cambio en la puntuación de fragilidad.
-Determinar el porcentaje de sujetos con interrupciones de ART no programadas.
-Determinar el número estimado de semanas sin TAR
-Determinar el cambio de la proporción de posesión de medicamentos (MPR) o la puntuación de adherencia
-Determinar el porcentaje de sujetos con ARN del VIH <40 copias / ml.
-Determinar el cambio en los perfiles de resistencia genotípica en sujetos que experimentan fracaso virológico.
-Determinar el cambio en el recuento de células T CD4 +
-Determinar cambios en la densidad mineral ósea.
-Determinar el número de sujetos con eventos adversos y eventos adversos graves (SAE).
-Determinar el número de sujetos con anormalidades de laboratorio de grado 1 a 4.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• HIV1-infected adults (≥18 years of age) with a history of IDU as the principal HIV transmission risk factor or with current or recent (past 12 months) history of IDU
• Either ART naïve or currently receiving an antiretroviral regimen but experiencing problems with adherence or tolerability issues on current ART therapy or restarting ART after an unscheduled treatment interruption
• Willing to switch current ART regimen
• No documented viral resistance to currently licensed HIV-1 integrase inhibitors, abacavir and lamivudine (with the exception of M184V) based either on previous HIV-1 genotypic resistance testing or in the judgment of the study investigators
• Integrase inhibitor naïve (defined as no-prior exposure to any INSTI)
• Documented negative HLAB*5701 allele

• Adultos VIH-positivos (≥18 años) con historia de uso de drogas inyectables como principal factor de riesgo de adquisición del VIH o con historia actual o reciente (durante los 12 últimos meses) de uso de drogas inyectables.
• Naïve para TAR o con problemas de adherencia o toxicidad con el TAR actual, o que empiezan TAR después de haberlo interrumpido.
• Dispuesto a cambiar el TAR actual
• Sin evidencia de resistencia a los Inhibidores de la Integrasa comercializados, ni a abacavir y lamivudina (con excepción de la mutación M184V) según test de resistencia genotípicos previos o en base a la opinión de los investigadores del estudio.
• Naïve para Inhibidores de la Integrasa (definido como sin exposición previa)
• HLAB*5701 negativo

E.4

Principal exclusion criteria

• Anticipated need for hepatitis C (defined as hepatitis C antibody (Ab) and RNA positive) treatment during the first 24 weeks of the study and subjects with active hepatitis B infection (defined as hepatitis B surface antigen (sAg) positive)
• Subjects with moderate to severe hepatic impairment (Class B or greater) as determined by Child-Pugh classification;
• Chronic renal failure defined as eGFR<60mls/min/1.73m2 at screening using the abbreviated Modification of Diet in Renal Disease (MDRD) equation: eGFR (ml/min/1,73 m2) = 175 x (CrS) -1,154 x (age)-0,203 x 0,742 (if female) x 1,21 (if black)
• Any active illness (including AIDS-defining illness) which in the opinion of the investigator would prevent the subject from completing all study assessments
• Female subjects who are pregnant, breastfeeding or planning future pregnancies or unwilling to take measures to avoid pregnancy for the study duration
• Any grade 4 laboratory abnormalities at screening
• Alanine aminotransferase (ALT) 5 times the upper limit of normal (ULN), OR ALT 3xULN and bilirubin 1.5xULN (with >35% direct bilirubin);
• Subjects weighing less than 40 kilograms and those are likely to require a Triumeq dose adjustment
• History or presence of allergy to the study drug or their components
• A diagnosis of cancer under current active chemotherapy or radiotherapy or having received chemotherapy or radiotherapy for a diagnosis of cancer within the previous 21 days prior to screening
• Subjects with a documented HLAB*5701 positive test on archived or screening bloods
• Concurrent use of any contraindicated medication (see section 5.2.2)

• Necesidad de comenzar tratamiento para la Hepatitis C durante las primeras 24 semanas de estudio.
• Hepatitis B activa (definida como antígeno de superficie (sAg) positivo)
• Moderada a severa enfermedad hepática (Clase B o mayor) en base a la clasificación Child-Pugh
• Enfermedad renal crónico definido como TFG <60mls/min/1.73m2 en la visita de cribado usando la ecuación MDRD
• Cualquier enfermedad activa (incluyendo enfermedades definitorias de SIDA) que en opinion del investigador impedirían que la persona complete todos los procedimientos del estudio.
• Mujeres embarazadas, en período de lactancia, que estén planeando quedarse embarazadas o que no querían tomar medidas anticonceptivas durante el período que dura el estudio.
• Cualquier abnormalidad en parámetros de laboratorio grado 4
• Peso menor de 40 kilogramos y aquellos pacientes que puedan requerir ajuste de dosis de Triumeq
• Historia o presencia de alergia a los fármacos del estudio o a sus componentes.
• Diagnóstico de cáncer en tratamiento actual con radioterapia o quimioterapia, o haber recibido tratamiento con radioterapia o quimioterapia en los 21 días previos a la visita de cribado.
• Test positivo para HLAB*5701 en muestras de sangre previas o en el cribado.
• Uso concomitante de cualquiera de los medicamentos contraindicados en el apartado 5.2.2

E.5 End points

E.5.1

Primary end point(s)

•Tolerability through self-reported adverse effects and directed symptom questionnaire
•Percentage of subject with unscheduled ART discontinuations/interruptions over 96 weeks
•Change from baseline of medication possession ratio (MPR) at 48 weeks or adherence score as measured by an antiretroviral therapy medication self-report form
•Percentage of subjects with HIV RNA<40 copies/mL at 48 weeks

• Tolerabilidad a través de efectos adversos autoinformados y cuestionario de síntomas dirigidos
• Porcentaje de sujetos con interrupciones de ART no programadas durante 96 semanas
• Cambio desde el basal de la relación de posesión de medicamentos (MPR) a las 48 semanas o el score de adherencia del TAR medido por un formulario autoinformado
• Porcentaje de sujetos con ARN del VIH <40 copias / ml a las 48 semanas

E.5.1.1

Timepoint(s) of evaluation of this end point

At 48 and 96 weeks

A las 48 y 96 semanas

E.5.2

Secondary end point(s)

•Change in number and severity of reported ART-related adverse effects from baseline to week 48 and 96
•Change in health-related quality of life (HRQOL) from baseline to week 48 and 96
•Change in frailty score from baseline to week 48 and 96
•Estimated number of weeks of missed ART over 48 and 96 weeks of follow-up
•Change from baseline of medication possession ratio (MPR) at 48 and 96 weeks or adherence score as measured by an antiretroviral therapy medication self-report form at the same time points
•Percentage of subjects with HIV RNA<40 copies/mL at 96 weeks
•Change in genotypic resistance profiles in subjects experiencing virological failure
•Change in CD4+ T-cell counts over 96 weeks
•Change in bone mineral density over 96 weeks
•Number of subjects with any adverse and any serious adverse events (SAE) from baseline to week 96
•Number of subject with Grade 1 to 4 laboratory abnormalities from baseline to week 96

• Cambio en el número y la gravedad de los efectos adversos relacionados con el TAR informados desde el basal hasta la semana 48 y 96
• Cambio en la calidad de vida relacionada con la salud (HRQOL) desde el basal hasta la semana 48 y 96
• Cambio en la puntuación de fragilidad desde el basal hasta la semana 48 y 96
• Número estimado de semanas sin TAR durante 48 y 96 semanas de seguimiento
• Cambio desde el basal de la relación de posesión de medicamentos (MPR) a las 48 y 96 semanas o del score de adherencia del TAR medido por un formulario autoinformado en los mismos puntos
• Porcentaje de sujetos con ARN del VIH <40 copias / ml a las 96 semanas
• Cambio en los perfiles de resistencia genotípica en sujetos con fracaso virológico.
• Cambio en el recuento de células T CD4 + durante 96 semanas
• Cambio en la densidad mineral ósea a lo largo de 96 semanas.
• Número de sujetos con eventos adversos y eventos adversos graves (SAE) desde el basal hasta la semana 96
• Número de sujetos con anomalías de laboratorio de grado 1 a 4 desde el basal hasta la semana 96

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline, week 48 and week 96

Basal, semana 48 y 96

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

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Yes

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

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)

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

Yes

F.3.3.7.1

Details of other specific vulnerable populations

HIV positive subjects

Sujetos VIH positivos

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)

Ongoing specialist care will be provided within the site for chronic HIV infection

Se proporcionará atención especializada continua en el centro para la infección crónica por VIH.

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

2019-05-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-04-05

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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