Clinical Trials Register

Summary
EudraCT Number:	2012-000649-11
Sponsor's Protocol Code Number:	SSAT046
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-03-18
Trial results	View 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

2012-000649-11

A.3

Full title of the trial

A phase IV, openlabel, single centre, singlearm, pilot study to assess Cerebrospinal fluid INflammatory markers after Addition of Maraviroc to MONotherapy darunavir/ritonavir ? The CINAMMON Study SSAT046

Estudio piloto de fase IV abierto, multicéntrico, de una única rama para evaluar los marcadores inflamatorios del líquido cefalorraquídeo (LCR) tras la incorporación de Maraviroc a la monoterapia con darunavir/ritonavir: El estudio CINAMMON

A.3.1

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

SSAT046 Addition of Maraviroc to monotherapy Darunavir/Ritonavir study

Marcadores inflamatorios LCR tras la incorporación de maraviroc a la monoterapia con darunavir/ritonavir

A.4.1

Sponsor's protocol code number

SSAT046

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	St Stephen's AIDS Trust
B.1.3.4	Country	United Kingdom
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	Pfizer Inc
B.4.2	Country	United States
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	Nerea Rozas
B.5.3	Address:
B.5.3.1	Street Address	Feixa Llarga, s/n
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08907
B.5.3.4	Country	Spain
B.5.6	E-mail	nrozas@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	Prezista
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag Ltd
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	Darunavir
D.3.4	Pharmaceutical form	Capsule, hard
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.3.11 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	Norvir
D.2.1.1.2	Name of the Marketing Authorisation holder	Abbott Laboratories 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	Ritonavir
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	RITONAVIR
D.3.9.1	CAS number	155213-67-5
D.3.9.4	EV Substance Code	SUB10342MIG
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.IMP: 3
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	Celsentri
D.2.1.1.2	Name of the Marketing Authorisation holder	ViiV Healthcare UK Ltd
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	Maraviroc
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	MARAVIROC
D.3.9.1	CAS number	376348-65-1
D.3.9.4	EV Substance Code	SUB25224
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

HIV infection

Infección por VIH

E.1.1.1

Medical condition in easily understood language

HIV infection

Infección por VIH

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

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 investigate changes from week 12 to week 36 in inflammatory markers in CSF when maraviroc (150mg qd) is added to stable darunavir/ritonavir (800/100mg qd) monotherapy for 24 weeks

?Investigar los cambios de la semana 12 a la semana 36 en los marcadores inflamatorios en el LCR cuando se añade maraviroc (150mg qd) a monoterapia estable con darunavir/ritonavir (800/100mg qd) durante 24 semanas

E.2.2

Secondary objectives of the trial

? To investigate the occurrence of viral load blips whilst on darunavir/ritonavir plus maraviroc
? To investigate changes in CD4 count
? To investigate changes in neurocognitive function
? To assess the safety and tolerability of darunavir/ritonavir plus maraviroc
? To look at MRI brain changes over the course of the study
? To examine drug levels of darunavir, maraviroc and ritonavir in CSF (and paired plasma samples)

?Investigar la prevalencia de blips de carga viral durante el tratamiento con darunavir/ritonavir más maraviroc
?Investigar cambios en el recuento de CD4
?Investigar cambios en la función neurocognitiva
? Evaluar la seguridad y la tolerabilidad de darunavir/ritonavir más maraviroc
?Ver los cambios cerebrales mediante Resonancia Magnética cerebral en el transcurso del estudio
?Examinar las concentraciones de darunavir, maraviroc y ritonavir en el LCR (y muestras pareadas de plasma)

? Evaluar la seguridad y la tolerabilidad de darunavir/ritonavir más maraviroc
? Ver los cambios cerebrales mediante IRM en el transcurso del estudio
? Examinar los niveles de fármaco de darunavir, maraviroc y ritonavir en el FCE (y muestras pareadas de plasma)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. male or female aged between 18 and 65 years
2. has a documented HIV-1 infection
3. has signed the Informed Consent Form voluntarily
4. is willing to comply with the protocol requirements
5. has an HIV-plasma viral load at screening <40 copies/mL (one off retesting for blips <200 copies/ml is allowed)
6. has a CD4 cell count at Screening >200 cells/mm3
7. has been on a stable darunavir/ritonavir regimen 800/100 once daily alone for at least 12 weeks at Screening, and willing to remain on this;
8. estimated glomerular filtration rate (by MDRD or CG methods) >60 ml/min at screening
9. CCR5 tropic by geno2pheno assay performed at screening
10. if female and of childbearing potential, she is using effective birth control methods (as agreed by the investigator) and is willing to continue practising these birth control methods during the trial and for at least 30 days after the end of the trial (or after last intake of investigational ARVs);
Note: Women who are postmenopausal for least 2 years, women with total hysterectomy, and women who have a tubal ligation are considered of non-childbearing potential
11. if a heterosexually active male, he is using effective birth control methods and is willing to continue practising these birth control methods during the trial and until follow-up visit

Los individuos infectados con el VIH CCR5 trópico en monoterapia con darunavir/ritonavir (800/100 mg qd) con una carga viral de <40 copias/ml (aunque al volver a hacer la prueba para blips se aceptan <200 copias/ml), dispuestos a firmar un formulario de consentimiento

E.4

Principal exclusion criteria

1. is infected with HIV-2
2. is using any concomitant therapy disallowed as per SPC for the study drugs (section 5.2)
3. has a currently active AIDS defining illness (Category C conditions according to the CDC Classification System for HIV Infection 1993) with the following exceptions (must be discussed with the Investigator prior to enrolment):
? Stable cutaneous Kaposi?s Sarcoma (no pulmonary or gastrointestinal involvement other than oral lesions) unlikely to require systemic therapy during the trial period
Note: Primary and secondary prophylaxis for an AIDS defining illness is allowed
4. has acute viral hepatitis including, but not limited to, A, B, or C
5. has chronic hepatitis B and/or C
6. has received any investigational drug within 30 days prior to the trial drug administration
7. Clinically significant allergy or hypersensitivity to any trial medication excipients
8. If female, she is pregnant or breastfeeding
9. Screening blood results with any grade 3/4 toxicity according to Division of AIDS (DAIDS) grading scale, except: asymptomatic grade 3 glucose, amylase or lipid elevation or asymptomatic grade 4 triglyceride elevation (re-test allowed).
10. Clinical or laboratory evidence of significantly decreased hepatic function or decompensation: INR > 1.5 or albumin < 30g/L or bilirubin > 2.5 x ULN.
11. Platelets of < 50 based on screening blood results.
12. Any condition (including drug/alcohol abuse) or laboratory results which, in the investigator?s opinion, interfere with assessments or completion of the trial.

E.5 End points

E.5.1

Primary end point(s)

? Change from week 12 to week 36 in inflammatory markers in CSF when maraviroc (150mg qd) is added to stable darunavir/ritonavir (800/100mg qd) monotherapy for 24 weeks

Cambio de la semana 12 a la semana 36 en marcadores inflamatorios en el LCR cuando se añade maraviroc (150mg qd) a la monoterapia estable con darunavir/ritonavir (800/100mg qd) durante 24 semanas

E.5.1.1

Timepoint(s) of evaluation of this end point

24 weeks

24 semanas

E.5.2

Secondary end point(s)

? Frequency of viral load blips whilst on darunavir/ritonavir plus maraviroc
? Changes in CD4 count from baseline to week 12 and week 12 to week 36
? Changes from control phase (baseline- Week 12) and week 36 in neurocognitive scores
? Proportion of subjects experiencing grade 2-4 clinical adverse events (at least possibly drug-related) at baseline, week 12, week 16 and week 36
? Proportion of subjects experiencing grade 2-4 laboratory abnormalities at baseline, week 12, week 16 and week 36
? Changes in MRI brain scanning over 36 weeks
? Drug concentrations of darunavir, ritonavir and maraviroc at week 36 in CSF (compared to matched plasma samples calculated as plasma:CSF ratio)

?Frecuencia de blips de carga viral durante el tratamiento con darunavir/ritonavir más maraviroc
?Cambios en el recuento de CD4 desde la visita basal hasta la semana 12 y desde la semana 12 hasta la semana 36
?Cambios en los resultados de los test neurocognitivos desde la fase de control (visita basal ?semana 12) a la semana 36
?Proporción de sujetos que experimentan anormalidades clínicas adversas de grado 2?4 (al menos potencialmente relacionados con el fármaco) en la visita basal, semana 12, semana 16 y semana 36
?Proporción de sujetos que experimentan anormalidades de laboratorio de grado 2?4 en la visita basal, semana 12, semana 16 y semana 36
?Cambios en RM cerebral a las 36
semanas
?Concentraciones de darunavir, ritonavir y maraviroc en el LCR en la semana 36 (comparado con muestras pareadas de plasma y calculadas como ratio plasma:LCR)

E.5.2.1

Timepoint(s) of evaluation of this end point

16, 24 and 36 weeks

16, 24 y 36 semanos

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

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

etiqueta abierta, multi centro, de brazo único

open-label, multi-centre, single-arm

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

Darunavir/Ritonavir alone (0-12 weeks) against Darunavir/Ritonavir plus Maraviroc (week 12-36)

E.8.2.4

Number of treatment arms in the trial

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

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 subject last visit

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

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.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)

At the end of the research study the participant will stop taking maraviroc and they will be discharged from the study with the HIV medications they were on prior to entering. They will be required to attend a follow up visit 4 to 12 weeks
after their last dose of maraviroc to check how they are.

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

2014-05-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-05-08

P. End of Trial
P.	End of Trial Status	Completed

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Orphan Designation Number:
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