Clinical Trials Register

Summary
EudraCT Number:	2015-005180-16
Sponsor's Protocol Code Number:	FFIS/2015/02/EV
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:	2020-10-22
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

2015-005180-16

A.3

Full title of the trial

Early vaginal progesterone for the prevention of spontaneous preterm birth in twins: A randomised, placebo controlled, double-blinded trial.

A.3.1

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

Prevention of preterm birth in twin pregnancies - “Randomised trial of progesterone versus placebo”

A.3.2

Name or abbreviated title of the trial where available

EVENTS

A.4.1

Sponsor's protocol code number

FFIS/2015/02/EV

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN66445401

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1175-4589

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	Fundación para la Formación e Investigación Sanitaria
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	Fetal Medicine Foundation
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	Laboratoires Besins International
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fetal Medicine Foundation
B.5.2	Functional name of contact point	Professor Kypros Nicolaides
B.5.3	Address:
B.5.3.1	Street Address	137 Harley Street
B.5.3.2	Town/ city	London
B.5.3.3	Post code	W1B 6BG
B.5.3.4	Country	United Kingdom
B.5.6	E-mail	thanks@fetalmedicine.org

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	Information not present in EudraCT
D.2.1.1.1	Trade name	Utrogestan
D.2.1.1.2	Name of the Marketing Authorisation holder	Besins Healthcare
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	Utrogestan
D.3.4	Pharmaceutical form	Pessary
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Vaginal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Progesterone
D.3.9.1	CAS number	57-83-0
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	300 mg
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	Pessary
D.8.4	Route of administration of the placebo	Vaginal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Spontaneous preterm birth in twin pregnancies.

E.1.1.1

Medical condition in easily understood language

Spontaneous preterm birth in twin pregnancies.

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	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10023555
E.1.2	Term	Labour premature
E.1.2	System Organ Class	100000004868

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Does the use of high dose vaginal progesterone (Utrogestan) started in the first trimester reduce the chances of having a preterm birth before 34 weeks gestation in twin pregnancies?

E.2.2

Secondary objectives of the trial

Does the use of high dose vaginal progesterone from the first trimester of pregnancy reduce any of the following in twin pregnancies:
1. The rate of preterm delivery before 37 weeks,
2. The number of babies born that are low birthweight,
3. The number of stillborn babies or babies that die soon after birth,
4. The number of babies that are admitted to the neonatal intensive care unit or suffer from significant adverse outcomes that are associated with prematurity.

E.2.3

Trial contains a sub-study

Information not present in EudraCT

E.3

Principal inclusion criteria

• Age > 18 years;
• DCDA or MCDA twin pregnancies;
• Live fetuses at 11-13 weeks of gestation;
• Bulgarian, English or Spanish speaking (otherwise
interpreters will be used);
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• Informed and written consent.

E.4

Principal exclusion criteria

• Pregnancies complicated by major fetal abnormality
identified at the 11-13 weeks assessment, including
nuchal translucency thickness >3.5 mm;
• MCDA twin pregnancies in which there are early
signs of twin-to-twin transfusion syndrome (TTTS)
(20% discordance in crown-rump length [CRL]
and/or nuchal translucency [NT]);
• Women who are unconscious or severely ill, those
with learning difficulties, or serious mental illness;
• Hypersensitivity to progesterone;
• Women taking progesterone regularly or at any time
within the previous 7 days;
• Concurrent participation in another drug trial or at
any time within the previous 28 days;
• Any other reason the clinical investigators think will
prevent the potential participant from complying with
the trial protocol.

E.5 End points

E.5.1

Primary end point(s)

Incidence of spontaneous delivery before 34 weeks'.

E.5.1.1

Timepoint(s) of evaluation of this end point

Data on pregnancy outcome will be collected from hospital maternity records or general practitioners. The obstetric records of all patients delivered at <34 weeks' (<238 days) will be examined to determine if the preterm birth is iatrogenic or spontaneous. The latter includes those with spontaneous onset of labour and those with preterm pre-labour rupture of membranes. In the event when the neonates are admitted to Special Care Baby Unit (SCBU)/Neonatal Intensive Care Unit (NICU), additional neonatal outcomes will be collected from the discharge summary of SCBU/NICU.

E.5.2

Secondary end point(s)

• The incidence of spontaneous preterm birth <37 weeks (259 days) of gestation;
• Birthweight below the 3rd, 5th and 10th centile;
• Stillbirth or neonatal death due to any cause;
• Major adverse outcomes before discharge from the hospital (intraventricular haemorrhage, respiratory distress syndrome, retinopathy of prematurity, or necrotising entercolitis);
• Need for neonatal special care (admission to a neonatal intensive care unit, ventilation, phototherapy, treatment for proven or suspected sepsis, or blood transfusion).

E.5.2.1

Timepoint(s) of evaluation of this end point

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

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

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

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

The end of the trial is defined as when the pregnancy outcome is complete for the last randomised trial patient and all oustanding data regarding the primary outcome measured is 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