Clinical Trials Register

Summary
EudraCT Number:	2013-002951-14
Sponsor's Protocol Code Number:	12/0357
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-01-14
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2013-002951-14

A.3

Full title of the trial

Human papillomavirus infection: a randomised controlled trial of Imiquimod cream (5%) versus Podophyllotoxin cream
(0.15%), in combination with quadrivalent human papillomavirus or control vaccination in the treatment and prevention
of recurrence of anogenital warts (HIPvac Trial)

A.3.1

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

HIPvac: a trial of vaccination and topical treatment in patients with anogenital warts

A.3.2

Name or abbreviated title of the trial where available

HIPvac Trial

A.4.1

Sponsor's protocol code number

12/0357

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 London
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	National Institute for Health Research (NIHR) Health Technology Assessment (HTA)
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University College London
B.5.2	Functional name of contact point	Clinical Trials Unit
B.5.3	Address:
B.5.3.1	Street Address	UCL, Gower Street,
B.5.3.2	Town/ city	London
B.5.3.3	Post code	WC1E 6BT
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	442031083942
B.5.6	E-mail	j.meadows@ucl.ac.uk

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
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Pasteur MSD
D.2.1.2	Country which granted the Marketing Authorisation	France
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	Gardasil
D.3.4	Pharmaceutical form	Suspension for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravascular use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	HUMAN PAPILLOMAVIRUS VACCINE [TYPES 6, 11, 16, 18] (RECOMBINANT, ADSORBED)
D.3.9.3	Other descriptive name	HUMAN PAPILLOMAVIRUS VACCINE [TYPES 6, 11, 16, 18] (RECOMBINANT, ADSORBED)
D.3.9.4	EV Substance Code	SUB25355
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 VACCINE [TYPES 6, 11, 16, 18] (RECOMBINANT, ADSORBED)
D.3.9.3	Other descriptive name	HUMAN PAPILLOMAVIRUS VACCINE [TYPES 6, 11, 16, 18] (RECOMBINANT, ADSORBED)
D.3.9.4	EV Substance Code	SUB25355
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.3.11 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)	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	Yes
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	Aldara 5% cream
D.2.1.1.2	Name of the Marketing Authorisation holder	Meda AB
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
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	Imiquimod
D.3.4	Pharmaceutical form	Cream
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Topical use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	IMIQUIMOD
D.3.9.1	CAS number	99011-02-6
D.3.9.4	EV Substance Code	SUB12453MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
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	Warticon Cream
D.2.1.1.2	Name of the Marketing Authorisation holder	Glaxo SmithKline UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Podophyllotoxin
D.3.4	Pharmaceutical form	Cream
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Topical use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	podophyllotoxin
D.3.9.3	Other descriptive name	PODOPHYLLOTOXIN
D.3.9.4	EV Substance Code	SUB14925MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.15
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)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	Yes
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Injection
D.8.4	Route of administration of the placebo	Intramuscular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Anogenital warts

E.1.1.1

Medical condition in easily understood language

Genital warts

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	PT
E.1.2	Classification code	10059313
E.1.2	Term	Anogenital warts
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10018182
E.1.2	Term	Genital warts
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

1. To compare the effectiveness of imiquimod 5% cream versus podophyllotoxin 0.15% cream in the treatment of external anogenital warts. The primary objective will be to compare the proportions of participants receiving each treatment who have complete resolution of warts by 16 weeks and remain free of warts up to 48 weeks after starting treatment.
2. To compare the effectiveness of a course of quadrivalent HPV vaccine started at the same time as topical wart treatment with the placebo, in improving wart clearance at 16 weeks and preventing recurrence up to 48 weeks.
3. To estimate the costeffectiveness of the two topical treatments, taking into account treatment, staff and other healthcare costs of initial and recurrent warts, and reduction in participants’ quality of life due to warts.
4. To estimate the costeffectiveness of a course of quadrivalent HPV vaccine compared with placebo control, taking into account treatment, staff and other healthcare costs of initial and recurrent

E.2.2

Secondary objectives of the trial

warts, and reduction in participants’ quality of life due to warts
5. To compare the wart clearance rate at interim time points corresponding to the end of the prescribed treatment course.
6. To compare the time to wart clearance in those treated with podophyllotoxin versus imiquimod with or without qHPV vaccine
7. To compare the proportion experiencing wart recurrence/relapse (after wart clearance) at 24 and 48 weeks.
8. To compare the tolerability of all treatments as measured by reported local and systemic reactions and other adverse events, and adherence to treatment.
9. To compare healthrelated quality of life, as measured by the Area Under the Curve for EQ5D.
10. To compare the requirements for additional therapy, including extension of the initial topical treatment course, treatment with cryotherapy, or recourse to other agents.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Males and females
• First episode or repeat episode of anogenital warts diagnosed clinically
• External anogenital warts considered, in the opinion of the investigator, to be suitable for selfadministered
topical
wart treatment (patients with concurrent internal anogenital warts are still eligible to participate).
• Able to provide informed consent to participate in the trial.

E.4

Principal exclusion criteria

• Previous wart treatment in the last 3 months
• Previous quadrivalent HPV vaccine (previous bivalent HPV vaccine is not an exclusion criterion).
• Previous intolerance to either of the topical treatments, vaccines or their constituents
• Known HIVpositivity
(HIV testing is not required for the trial).
• Pregnancy or lactation (current, or planned in the next 6 months)
• Women of child bearing potential not willing to use effective contraception for the duration and 30 days post
completion of trial treatment: see above
• Unable or unwilling to complete followup
procedures
• Lesion area greater than 4 cm2, requiring treatment under direct supervision of medical staff (in accordance with
podophyllotoxin cream Summary of Product Characteristics).
• Patients who have had topical steroids applied to the target area, or systemic steroids or other immunosuppressive
agents, within 1 month prior to randomisation
• Patients enrolled in any other trial of an Investigational Medicinal Product, without the permission of the Chief
Investigator.
• Any clinical condition which the

E.5 End points

E.5.1

Primary end point(s)

The primary outcome is a composite endpoint of wart clearance within 16 weeks of starting treatment and remaining
wartfree
between 16 and 48 weeks. This will capture both the initial clearance efficacy as well as the impact on
relapse or recurrence.

E.5.1.1

Timepoint(s) of evaluation of this end point

16 and 48 weeks.

E.5.2

Secondary end point(s)

1. Proportion wartfree
at the end of the assigned treatment course (4 or 16 weeks)
2. Proportion wartfree
at 16 weeks after use of additional treatment as required
3. Quantity of additional treatment (number of cryotherapy applications, additional weeks of podophyllotoxin or
imiquimod) required to achieve clearance by 16 weeks
4. Proportion wartfree
at 24 weeks
5. Proportion wartfree
at 24 weeks after use of additional treatment as required
6. Quantity of additional treatment (number of cryotherapy applications, additional weeks of podophyllotoxin or
imiquimod) required to achieve clearance by 24 weeks
7. Time to complete wart clearance
8. Proportion experiencing wart recurrence/relapse after wart clearance.
9. Proportion experiencing wart recurrence/relapse at 48 weeks after wart clearance at 24 weeks.
10. Time from complete wart clearance to recurrence/relapse
11. Adverse events
12. Healthrelated
quality of life, as measured by the Area Under the Curve for EQ5D
13. Symptom score
14. Total costs of treatment including prescribed agents and clinic visits

E.5.2.1

Timepoint(s) of evaluation of this end point

weeks:4, 16, 24 and 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

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)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

Yes

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)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

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

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

Trial closure is defined as the date when all data having been received, cleaned and all queries have been resolved at
all sites.

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:

1000

F.1.3

Elderly (>=65 years)

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

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

1000

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)

Participants will be managed according to standard of care if they have persistent genital warts or experience
recurrence, or a further episode.

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

2014-07-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-06-17

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-01-17

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