Clinical Trials Register

Summary
EudraCT Number:	2019-003486-17
Sponsor's Protocol Code Number:	9-VPH-MVIH
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:	2020-01-23
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2019-003486-17

A.3

Full title of the trial

Immunogenicity and safety of a 9-valent human papillomavirus vaccine in HIV-positive women

Ensayo Clínico en fase IV sobre la seguridad e inmunogenicidad de la vacuna Gardasil-9 en mujeres infectadas por el VIH

A.3.1

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

Immunogenicity and safety of a 9-valent human papillomavirus vaccine in HIV-positive women

Ensayo Clínico en fase IV sobre la seguridad e inmunogenicidad de la vacuna Gardasil-9 en mujeres infectadas por el VIH

A.4.1

Sponsor's protocol code number

9-VPH-MVIH

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	CARMEN HIDALGO TENORIO
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	GOBIERNO DE ESPAÑA. MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES. Instituto de Salud Carlos III
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	FIBAO
B.5.2	Functional name of contact point	clinical trials information
B.5.3	Address:
B.5.3.1	Street Address	Avda. de Madrid, 15 , Pabellón de Consultas Externas 2, 2a Planta (Antigua Área de Dirección), 18012
B.5.3.2	Town/ city	Granada
B.5.3.3	Post code	18014
B.5.3.4	Country	Spain
B.5.4	Telephone number	958895414

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	Gardasil 9 suspensión inyectable en jeringa precargada
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme de España, S.A.
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	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Human Papillomavirus Type 16 L1 protein
D.3.9.3	Other descriptive name	HUMAN PAPILLOMAVIRUS TYPE 16 L1 PROTEIN
D.3.9.4	EV Substance Code	SUB22593
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	60
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Human Papillomavirus Type 6 L1 protein
D.3.9.3	Other descriptive name	HUMAN PAPILLOMAVIRUS TYPE 6 L1 PROTEIN
D.3.9.4	EV Substance Code	SUB22591
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Human Papillomavirus Type 11 L1 protein
D.3.9.3	Other descriptive name	HUMAN PAPILLOMAVIRUS TYPE 11 L1 PROTEIN
D.3.9.4	EV Substance Code	SUB22592
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Human Papillomavirus Type 18 L1 protein
D.3.9.3	Other descriptive name	HUMAN PAPILLOMAVIRUS TYPE 18 L1 PROTEIN
D.3.9.4	EV Substance Code	SUB22594
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Human Papillomavirus Type 52 L1 protein
D.3.9.3	Other descriptive name	HUMAN PAPILLOMAVIRUS TYPE 52 L1 PROTEIN
D.3.9.4	EV Substance Code	SUB130871
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Human Papillomavirus Type 58 L1 protein
D.3.9.3	Other descriptive name	HUMAN PAPILLOMAVIRUS TYPE 58 L1 PROTEIN
D.3.9.4	EV Substance Code	SUB130872
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Human Papillomavirus Type 31 L1 protein
D.3.9.3	Other descriptive name	HUMAN PAPILLOMAVIRUS TYPE 31 L1 PROTEIN
D.3.9.4	EV Substance Code	SUB130868
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Human Papillomavirus Type 33 L1 protein
D.3.9.3	Other descriptive name	HUMAN PAPILLOMAVIRUS TYPE 33 L1 PROTEIN
D.3.9.4	EV Substance Code	SUB130869
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Human Papillomavirus Type 45 L1 protein
D.3.9.3	Other descriptive name	HUMAN PAPILLOMAVIRUS TYPE 45 L1 PROTEIN
D.3.9.4	EV Substance Code	SUB130870
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
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

New infection and lesions of papillomavirus in HIV-infected women

Nuevas infecciones y lesionas provocadas por el virus del papiloma humano en mujeres infectadas por le VIH

E.1.1.1

Medical condition in easily understood language

New infection and lesions of papillomavirus in HIV-infected women

Nuevas infecciones y lesionas provocadas por el virus del papiloma humano en mujeres infectadas por le VIH

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

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 analyze the immunogenicity and safety of a 9-valent human papillomavirus vaccine in HIV-positive women older than ≥18 years.

Analizar la seguridad e inmunogenicidad de la vacuna 9-valente del virus del papiloma humano en mujeres mayores de 18 años infectadas por el VIH

E.2.2

Secondary objectives of the trial

1. Analyze after vaccination, the acquisition rate of HPV genotypes of anal and cervical mucosa.
2. Investigate the risk factors related to acquisition of HPV genotypes (such as HAART, comorbidities, age, smoking, condom use, CD4 cell count, viral load, etc) in anal and cervical mucosa.
3. To evaluate, in women with normal anal and cervical mucosa, the rate of progression to dysplastic lesions (LSIL, HSIL and Cancer) anal and cervical after vaccination in the follow-up period.

1. Analizar tras la vacunación la tasa de aclaramiento y adquisición de los genotipos de VPH de mucosa anal y cervical .
2. Estudiar los factores relacionados (entre los que incluiremos desde el Tratamiento anti-retroviral, estado inmunológico, comorbilidades, edad, tabaquismo, uso de condon, al nivel cultural etc) con el aclaramiento y adquisición de genotipos del VPH en mucosa cervical y anal.
3. Evaluar en mujeres con mucosa anal y cervical normal la tasa de progresión a lesiones displásicas (LSIL, HSIL y Cáncer) anales y cervicales tras la vacunación en el periodo de seguimiento.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

HIV-positive women patients of ≥18 years of age who, at the time of study inclusion were not infected simultaneously by the 16, 18 genotypes of HPV in vagina and/or anus.

Mujeres infectadas por el VIH, de 18 años en adelante, que no estén infectadas en el momento de inclusión en el estudio en vagina y/o ano por de forma simultánea por los genotipos del Virus Papiloma Humano 16 y 18.

E.4

Principal exclusion criteria

- WLHIV patients who had simultaneous anal infection with the 16, 18, 31, 33, 45, 52 y 58 genotypes.
- WLHIV diagnosed in V0 of ASCC or anal HSIL.
- Active opportunist infection at the time of recruitment into the study.
- Cd4 count < 200 cel/uL.
- History of allergy to aluminium and/or yeast extract excipient.

- Mujeres infectadas en la mucosa anal simultáneamente por los genotipos 16, 18, 31, 33, 45, 52 y 58.
- Mujeres que en canal anal en V0 se le diagnosticara HSIL o Carcinoma anal.
- Enfermedad oportunista activa en el momento de inclusión en el estudio.
- Recuento de linfocitos CD4 < 200 cél/mL
- Antecedentes de alergia al aluminio o levadura.

E.5 End points

E.5.1

Primary end point(s)

Proportion of subjects with new infections from genotypes included in de 9-valent vaccine and aparition of cervical and anal dysplasia in these women .

Proporción de sujetos con nuevas infecciones por los genotipos incluidos en la vacuna nonavalente y la aparición de displasia cervical y anal en estas mujeres.

E.5.1.1

Timepoint(s) of evaluation of this end point

30th month, when data from follow up visits are collected.

mes 30, cuando los datos de todas las visitas de seguimiento hayan sido recogidos.

E.5.2

Secondary end point(s)

1. Proportion of acquisition of HPV genotypes of anal and cervical mucosa.
2. Prevalence of risk factors related to acquisition of HPV genotypes (such as HAART, comorbidities, age, smoking, condom use, CD4 cell count, viral load, etc) in anal and cervical mucosa.
3. Proportion of women with normal anal and cervical mucosa, with progression to dysplastic lesions (LSIL, HSIL and Cancer) anal and cervical after vaccination in the follow-up period.

1. Tasa de adquisición de genotipos del VPH en mucosa cervical y anal
2. Prevalencia de factores de riesgo relacionados con la adquisición de genotipos de VPH ( Como el TAR, comorbilidades, edad, tabaquismo, uso del condón, Recuento de CD4, carga viral, etc.) en la mucosa cervical y anal.
3. Proporción de mujeres con mucosa cervical y anal normal, que progresan a lesiones displásicas (LSIL, HSIL y cancer) anales y cervicales tras la vacunación y durante el periodo de seguimiento.

E.5.2.1

Timepoint(s) of evaluation of this end point

30th month, when data from follow up visits are collected.

mes 30, cuando los datos de todas las visitas de seguimiento hayan sido recogidos.

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.8.2.4

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

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

LPLV

UPUV

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:

173

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

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

173

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)

NONE

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

2020-02-11

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials