Clinical Trials Register

Summary
EudraCT Number:	2015-005013-76
Sponsor's Protocol Code Number:	AC15004
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:	2016-03-10
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

UK - MHRA

A.2

EudraCT number

2015-005013-76

A.3

Full title of the trial

GEM3: A double blind placebo controlled trial of a combination of methotrexate and gefitinib versus methotrexate alone as a treatment for ectopic pregnancy

A.3.1

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

GEM 3: combination methotrexate and gefitinib for the treatment of ectopic pregnancy.

A.3.2

Name or abbreviated title of the trial where available

GEM3

A.4.1

Sponsor's protocol code number

AC15004

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN67795930

A.5.4

Other Identifiers

Name:

Ethics number

Number:

16/SS/0014

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	ACCORD office
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point
B.Sponsor: 2
B.1.1	Name of Sponsor	NHS Lothian R&D Office
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University of Edinburgh
B.5.2	Functional name of contact point	Ann Doust
B.5.3	Address:
B.5.3.1	Street Address	Room S7128, Simpson Centre for Reproductive Health
B.5.3.2	Town/ city	Edinburgh
B.5.3.3	Post code	EH16 4SA
B.5.4	Telephone number	01312429492
B.5.5	Fax number	01312422686
B.5.6	E-mail	ann.doust@ed.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	Iressa
D.2.1.1.2	Name of the Marketing Authorisation holder	Astra Zenica
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	Iressa
D.3.2	Product code	EU/1/09/526/001
D.3.4	Pharmaceutical form	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	Gefitinib
D.3.9.1	CAS number	184475-35-2
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.3.11 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
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Ectopic pregnancy

E.1.1.1

Medical condition in easily understood language

Pregnancy growing outside of womb.

E.1.1.2

Therapeutic area

Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

MedDRA Classification

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	10014166
E.1.2	Term	Ectopic pregnancy
E.1.2	System Organ Class	10036585 - Pregnancy, puerperium and perinatal conditions

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

This is a randomised controlled trial.

To see if taking methotrexate (MTX) in combination with gefitinib is better at reducing the need for surgery against methotrexate alone in the treatment of ectopic pregnancy.

E.2.2

Secondary objectives of the trial

To see if taking MTX in combination with gefitinib is better than methotrexate alone in reducing the need for a further dose of MTX.
To see if it will reduce the numbers of days until the pregnancy is resolved (pre-pregnancy hormone level of <=15 iu/l which could reduce the number of visits to the hospital.
To see if the treatment is safe to use and that women can tolerate the treatment. To see if women are happy taking the treatment.

E.2.3

Trial contains a sub-study

E.2.3.1

Full title, date and version of each sub-study and their related objectives

GEM 3 - Mechanistic study

E.3

Principal inclusion criteria

MAIN STUDY

• Clinical decision made for treatment of EP with MTX
• Able to understand all information (written and oral) presented (using an interpreter if necessary) and provide signed consent
• Women 18-50 years at time of randomisation
• Diagnosis of;
1. definite tubal EP (extrauterine gestational sac with yolk sac and/or
embryo, without cardiac activity on USS) or
2. clinical decision of probable EP (extrauterine sac-like structure or
inhomogeneous adnexal mass on USS with a background of sub optimally
rising serum hCG concentrations)
• Pre-treatment serum hCG level of 1000–5000 iu/l (within 1 calendar day of treatment )
• Clinically stable
• Haemoglobin between 100 and 165 g/L within 3 calendar days of treatment
• Able to comply with treatment and willing to participate in follow up
• Not participating in any other clinical trial of a medicinal product or previous participation in GEM 3 trial.

E.4

Principal exclusion criteria

MAIN STUDY:

• Women with a pregnancy of unknown location (PUL)
• Breastfeeding
• Hypersensitivity to gefitinib
• Women with EP mass on ultrasound greater than 3.5cm
• Women with evidence of intrauterine pregnancy
• Evidence of significant intra-abdominal bleed on ultrasound defined by
echogenic free fluid above the uterine fundus or surrounding ovary within1 calender day of treatment
• Significant abdominal pain, guarding/rigidity
• Clinically significant abnormal liver/renal/haematological indices noted
within 3 calendar days of treatment
• Significant pre-existing dermatological disease
• Significant pulmonary disease
• Significant gastrointestinal medical illness
• Japanese ethnicity

E.5 End points

E.5.1

Primary end point(s)

The need for surgical intervention for treatment of EP (salpingectomy/salpingostomy by laparoscopy/laparotomy)

E.5.1.1

Timepoint(s) of evaluation of this end point

End of treatment

E.5.2

Secondary end point(s)

SECONDARY CLINICAL OUTCOMES:
1) Additional MTX
2) time to hCG resolution (days) from randomisation to hCG level of ≤15 iu/l
3) number of treatment-associated hospital visits until resolution or scheduled/emergency surgery
4) safety/tolerability
5) Acceptability of treatment
6) Return to menstruation

E.5.2.1

Timepoint(s) of evaluation of this end point

Three months post treatment

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)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

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

Last questionnaire received.

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