Clinical Trials Register

Summary
EudraCT Number:	2015-001587-19
Sponsor's Protocol Code Number:	UHSM0315
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2015-07-20
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

UK - MHRA

A.2

EudraCT number

2015-001587-19

A.3

Full title of the trial

A pilot prevention study of the effects of the anti-progestin Ulipristal Acetate (UA) on surrogate markers of breast cancer risk

A.3.1

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

Breast Cancer - Anti-Progestin Prevention Study 1

A.3.2

Name or abbreviated title of the trial where available

Breast Cancer - Anti-Progestin Prevention Study 1

A.4.1

Sponsor's protocol code number

UHSM0315

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02408770

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	Manchester University NHS Foundation 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	Breast cancer Campaign
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 of Manchester
B.5.2	Functional name of contact point	Dr Sacha Howell
B.5.3	Address:
B.5.3.1	Street Address	Department of Medical Oncology, The Christie NHS Foundation Trust
B.5.3.2	Town/ city	Manchester
B.5.3.3	Post code	M204BX
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01614468347
B.5.6	E-mail	sacha.howell@christie.nhs.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	Esmya
D.2.1.1.2	Name of the Marketing Authorisation holder	Gedeon Richter 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	Esmya 5mg (ulipristal acetate)
D.3.2	Product code	EMEA/H/C/002041
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	ulipristal acetate
D.3.9.1	CAS number	126784-99-4
D.3.9.2	Current sponsor code	UHSM0315
D.3.9.3	Other descriptive name	Esmya
D.3.9.4	EV Substance Code	AS1
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	5 to 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.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

We seek to investigate the breast cancer risk reducing properties of ulipristal acetate

E.1.1.1

Medical condition in easily understood language

We seek to investigate the breast cancer risk reducing properties of ulipristal acetate

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

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	10004746
E.1.2	Term	Biopsy breast normal
E.1.2	System Organ Class	10022891 - Investigations

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10006187
E.1.2	Term	Breast cancer
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	PT
E.1.2	Classification code	10071224
E.1.2	Term	Breast scan
E.1.2	System Organ Class	10022891 - Investigations

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 determine whether three months of treatment with the antiprogestin ulipristal acetate reduces proliferation in the normal breast tissue of women at moderate to high risk of developing breast cancer.

E.2.2

Secondary objectives of the trial

1. To examine the breast tissue of women treated with ulipristal acetate to determine its effects on: gene and protein expression, tissue stiffness and collagen organisation and the proportion and type of stem cells.

2. To relate the molecular changes above with MRI imaging biomarkers

3. To determine the side effect profile of UA in this patient population

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Premenopausal females aged between 25 and 45 years
Regular menses defined as date of onset of last menstrual period +/- 3 days of expected
Known BRCA1 or BRCA2 mutation or moderate to high risk of developing BC defined as >17% lifetime risk from age 20 or >3% risk between 40-50 years
Ovulatory menstrual cycles defined as serum progesterone ≥15nmol 7 days prior to expected onset of menses.
eGFR ≥ 40mls/min/1.73m2 in view of requirement for gadolinium contrast MRI scans
Willing and able to provide informed consent to undergo all trial procedures.

E.4

Principal exclusion criteria

Personal history of breast, uterine, cervical or ovarian cancer

Breast feeding within the last 3 months

Pregnant or planning for pregnancy in the next 6 months. Pregnancy must be excluded with serum βhCG <5nmol during screening.

Known hypersensitivity to radiological contrast media or to ulipristal acetate or any of its excipients (microcrystalline cellulose, mannitol, croscarmellose sodium, talc, magnesium stearate)

Current treatment with:

Anti-estrogens (e.g. tamoxifen or raloxifene), GnRH analogue therapy (e.g. goserelin or buserelin) or hormonal contraceptives including androgens such as cyproterone acetate. Such treatments must have been stopped for at least 6 months and regular menstrual cycles resumed.

Corticosteroids at any dose, these must have been stopped for at least 1 month with low likelihood that retreatment will be required

Antiplatelet or anticoagulant therapy – must have been stopped for at least 7 days and clotting be at satisfactory levels (see below)

moderate or potent inhibitors of CYP3A4 (for list see appendix)

potent inducers of CYP3A4 (for full list see appendix 1)

APTT and PT outside the normal institutional ranges. Hb <100g/l and platelet count <150x109/l. Serum creatinine, bilirubin, ALT, ALP or LDH >1,5xULN.

Contraindications to MRI, such as intracranial aneurysm clips, implanted electrical devices and intra-ocular metallic foreign bodies.

Co-morbidity that would put the patient at increased risk such as recognised bleeding diathesis, moderate to severe hepatic impairment, moderate or severe renal impairment (eGFR <40 ml/min/1.73m2), severe asthma not adequately controlled with corticosteroids (note steroid usage precludes trial entry)

Prior breast enhancement/augmentation surgery

Genital bleeding of unknown aetiology

E.5 End points

E.5.1

Primary end point(s)

The change in the proliferation of normal breast epithelium, assessed by Ki67, from baseline to 3 months on treatment with ulipristal acetate

E.5.1.1

Timepoint(s) of evaluation of this end point

Comparison between baseline (pre treatment) and after 3 months of therapy

E.5.2

Secondary end point(s)

The changes in expression of individual genes and key pathways induced by UA therapy
The change in tissue stiffness and collagen organisation induced by UA therapy,
The changes in key stem cell and PgR target proteins induced by UA therapy
The proportion and type of clonogenic cells in the breast following treatment with UA
MRI imaging biomarkers of anti-progestin (UA) activity
The side effect profile of UA in this patient population

E.5.2.1

Timepoint(s) of evaluation of this end point

All biological enpoints will be assessed at the 3 month timepoint as this is when the second biopsy or prophylactic mastectomy will be performed.

Toxicity (side effect profile) will be assessed monthly on therapy and at one month post cessation of ulipristal acetate

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

pilot cancer prevention study with safety, PD and pharmacogenetic endpoints

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

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)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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.8.4.1

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

The end of the trial will be defined as the end of the funding period.

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