Clinical Trials Register

Summary
EudraCT Number:	2014-004478-41
Sponsor's Protocol Code Number:	LCC001
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:	2015-03-06
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

2014-004478-41

A.3

Full title of the trial

Phase III trial in IntrahepaTic CHolestasis of pregnancy (ICP) to Evaluate urSodeoxycholic acid (UDCA) in improving perinatal outcomes

A.3.1

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

Pregnant women with a specific liver condition will be randomised to receive a treatment that is currently used compared with a placebo, looking at the health of their babies.

A.3.2

Name or abbreviated title of the trial where available

PITCHES: Phase III trial of UDCA in ICP: V1

A.4.1

Sponsor's protocol code number

LCC001

A.5.4

Other Identifiers

Name:

REC number

Number:

15/EE/0010

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	King's 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	EME programme, NIHR
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	King's College London
B.5.2	Functional name of contact point	Dr Lucy Chappell
B.5.3	Address:
B.5.3.1	Street Address	10th Floor North Wing, St Thomas' Hospital
B.5.3.2	Town/ city	London
B.5.3.3	Post code	SE1 7EH
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	00442071883639
B.5.5	Fax number	004420776201227
B.5.6	E-mail	lucy.chappell@kcl.ac.uk
B.Sponsor: 2
B.1.1	Name of Sponsor	Guy's and St Thomas' 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	EME programme, NIHR
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	Guy's and St Thomas' NHS Foundation Trust
B.5.2	Functional name of contact point	Dr Lucy Chappell
B.5.3	Address:
B.5.3.1	Street Address	10th Floor North Wing, St Thomas' Hospital
B.5.3.2	Town/ city	London
B.5.3.3	Post code	SE1 7EH
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	00442071883639
B.5.5	Fax number	00442076201227
B.5.6	E-mail	lucy.chappell@kcl.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	Ursofalk
D.2.1.1.2	Name of the Marketing Authorisation holder	Dr Falk Pharma GmBH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Film-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	Ursodeoxycholic acid
D.3.9.1	CAS number	128-13-2
D.3.9.3	Other descriptive name	URSODEOXYCHOLIC ACID
D.3.9.4	EV Substance Code	SUB11389MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	500 to 2000
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	Film-coated 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

Intrahepatic Cholestasis of pregnancy

E.1.1.1

Medical condition in easily understood language

A liver disorder which occurs during pregnancy, and which has been known to be diagnosed at any time from 20 weeks onwards. It is referred to as obstetric cholestasis

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	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10008638
E.1.2	Term	Cholestasis intrahepatic
E.1.2	System Organ Class	100000004871

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Intrahepatic cholestasis of pregnancy (ICP), or obstetric cholestasis (OC) is a liver condition of pregnancy. Pregnant women diagnosed with ICP are more at risk of suffering from in utero fetal death, stillbirth, perinatal death (under 7 days), preterm delivery (less than 37 weeks' gestation) and neonatal unit admission. The principal research question asks: does treatment with ursodeoxycholic acid (UDCA) in ICP women, increase the chance of having a healthy baby, by reducing the problems listed above?

E.2.2

Secondary objectives of the trial

The secondary research objectives of the study are to investigate the effect of UDCA treated ICP on other short term outcomes for both the mother and baby; and to assess the impact of UDCA treated ICP on health resource use: in terms of the total number of nights for mother and neonate, including intensive care and mode of delivery.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

ICP (pruritus with a raised serum bile acid above the upper limit of normal for the local laboratory)
20+0 to 40+6 weeks' gestation on day of randomisation (see note below on gestational age)
No known lethal fetal anomaly
Singleton or twin pregnancy
Aged 18 years or over
Able to give written informed consent
Determination of gestational age: for all calculations relating to gestational age (eligibility for enrolment, gestational age at delivery), gestational age will be calculated based on the following hierarchical model, as set out in the NICE guidelines for antenatal care:
 From crown-rump length measurement on early ultrasound scan between 10+0 weeks and 13+6 weeks
 From head circumference on ultrasound scan if crown–rump length is above 84 mm

E.4

Principal exclusion criteria

 Decision has already made for delivery within the next 48 hours
 Allergy to any component of the UDCA or placebo tablets
 Triplet or higher-order multiple pregnancy

E.5 End points

E.5.1

Primary end point(s)

The primary short term perinatal outcome is a composite of perinatal death (as defined by in utero fetal death from 20+0 and 23+6 weeks’ gestation or stillbirth before delivery > 24+0 weeks’ gestation or neonatal death up to 7 days but
not death due to congenital anomaly) or preterm delivery (less than 37 weeks’ gestation) or NNU admissions (from infant delivery until hospital discharge to home). Each infant will only be counted once within this composite.

E.5.1.1

Timepoint(s) of evaluation of this end point

The time points of evaluation of this outcome measure are:
For deaths: between randomisation and 7 days post infant delivery
For preterm delivery: between randomisation and upto 37 weeks gestation
For infant neonatal unit admission: between randomisation and infant discharge (from hospital to home)

E.5.2

Secondary end point(s)

The secondary short term maternal outcomes are:
• Peak maternal serum concentration (between randomisation and delivery) of following biochemical indices of
disease:
o Bile acids
o Alanine transaminase
o Bilirubin (total)
o Gamma glutamyl transferase
• Worst episode of itch over past 24 hours (mm on visual analogue scale) between randomisation and delivery
(assessed at clinic visits)
• Maximum dose of trial medication required
• Need for additional therapy
• Gestational diabetes mellitus
• Gestational Hypertension/Preeclampsia
• Assessment of myometrial contractions by CTG approximately one week (314
days) post randomisation
• Mode of onset of labour
• Mode of delivery classified as spontaneous vaginal, instrumental vaginal or caesarean
• Reason for induction or prelabour
caesarean section
• Estimated blood loss after delivery

The secondary short term perinatal outcomes are:
• In utero fetal death 20+0 to 23+6 weeks’ gestation
• Stillbirth (death before delivery > 24+0 weeks’ gestation)
• Preterm delivery (less than 37 weeks’ gestation)
• Neonatal death up to 7 days (excluding death due to congenital anomaly)
• Neonatal death up to 28 days (excluding death due to congenital anomaly)
• NNU admissions until infant hospital discharge to home
• Number of nights in each category of care (intensive, high dependency, special, transitional and normal)
• Total number of nights in hospital
• Birth weight (g)
• Customised/population birth weight centile (GROW)
• Gestational age at delivery
• Presence of meconium
• APGAR score at 5 minutes
• Umbilical arterial and venous pH (and base excess) at birth
• Need for supplementary oxygen prior to discharge
• Number of days when supplemental oxygen is required
• Need for ventilation support (CPAP/high flow/endotracheal ventilation)
• Pneumothorax (confirmed on chest Xray)
• Need for phototherapy
• Abnormal cerebral ultrasound scan
• Confirmed sepsis (positive blood or cerebrospinal fluid cultures)
• Necrotising Enterocolitis (Bell’s stage 2 and 3)
• Seizures (confirmed by EEG or requiring anticonvulsant therapy)
• Encephalopathy grade (worst at any time: mild, moderate, severe)
• Hypoglycaemia (blood glucose <2.6 mmol/l on two or more occasions)
• Other indications and main diagnoses resulting in neonatal unit admission
• Exclusively receiving breast milk at discharge from the neonatal unit.

E.5.2.1

Timepoint(s) of evaluation of this end point

The timepoints of evaluation of the secondary outcomes are taken at the clinic visits and during admission for delivery up to discharge home of mother and infant.

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

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

The trial will be judged complete when all infants have been discharged from hospital, died or reach one month of age, whichever is soonest.

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:

580

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

Yes

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

Yes

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

580

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)

ICP is a condition of pregnancy and so the trial ends with the delivery of the baby. In clinical practice UDCA is stopped
at delivery.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Clinical Research Network - Reproductive Health and Childbirth - National Speciality Lead
G.4.3.4	Network Country	United Kingdom

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-03-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-02-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-11-28

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