Clinical Trials Register

Summary
EudraCT Number:	2018-001887-46
Sponsor's Protocol Code Number:	STH18493
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:	2019-06-19
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

2018-001887-46

A.3

Full title of the trial

A Phase II, Placebo Controlled, Double Blind, Randomised Clinical Trial to assess the safety and tolerability Of 30mg/kg daily Ursodeoxycholic Acid (UDCA) in Patients with Parkinson’s Disease (PD)

A.3.1

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

Trial of Ursodeoxycholic Acid (UDCA) for PD. The 'UP-study'

A.3.2

Name or abbreviated title of the trial where available

Trial of Ursodeoxycholic Acid (UDCA) for PD. The 'UP-study'

A.4.1

Sponsor's protocol code number

STH18493

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	Sheffield Teaching Hospitals 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	The J P Moulton Charitable Foundation
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	PRO.MED.CS Praha
B.4.2	Country	Czech Republic
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sheffield Teaching Hospitals NHS Foundation Trust
B.5.2	Functional name of contact point	Sarah Moll
B.5.3	Address:
B.5.3.1	Street Address	D54b D Floor, Biomedical Research Centre Office, Royal Hallamshire Hospital
B.5.3.2	Town/ city	Sheffield
B.5.3.3	Post code	S10 2JF
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01142712563
B.5.6	E-mail	sarah.moll@sth.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	Ursonorm
D.2.1.1.2	Name of the Marketing Authorisation holder	Kappler Pharma Consult 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.3.1	Product name	Ursonorm
D.3.4	Pharmaceutical form	Capsule, hard
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.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
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	Capsule, hard
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

Parkinson’s disease (PD)

E.1.1.1

Medical condition in easily understood language

PD is a progressive neurodegenerative condition. It causes both motor and non-motor symptoms. Currently available symptomatic therapy helps to address these symptoms for a limited period.

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

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	10061536
E.1.2	Term	Parkinson's disease
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to compare the safety and tolerability of UDCA at 30 mg/kg in PD compared to placebo as indicated by:

• Number of serious adverse events (SAEs)

• Number of adverse Treatment-reactions

• Number of patients completing the study

E.2.2

Secondary objectives of the trial

The secondary objectives are to assess the effect of UDCA compared with Placebo on disease progression in PD at 48 weeks (assessed as a change from baseline) by:

Clinical assessment (using the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part 3 motor subscale) in the "OFF" medication state.

In vivo parameter estimates of high and low energy metabolite levels (ATP, PCr, Pi) , derived from cranial 31P MRS centred on the basal ganglia and related motor regions (using 31P MRS at 48 weeks)

Sensor-based, objective quantification of motor impairment, using the Optogait and Opals systems (Sheffield patients only) as well as the Dynaport Move monitor (all patients)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Diagnosis of Parkinson’s disease ≤ 3 years ago by a clinician with particular expertise in the diagnosis and treatment of movement disorders
• Subjective improvement of motor impairment on dopaminergic medication, confirmed by PI through personal examination and/or review of medical records
• Hoehn and Yahr stage ≤ 2.5 in the practically defined “ON” medication state. This implies that all patients will be mobile without assistance during their best “ON” medication periods.
• Ability to take the study drug
• Ability to communicate in English
• Age 18-75 yr of any gender
• Documented informed consent to participate.
• Able to comply with study protocol and willing to attend necessary study visits

E.4

Principal exclusion criteria

 Diagnosis or suspicion of other cause of parkinsonism. Patients with clinical features indicating a diagnosis of progressive supranuclear palsy (PSP), multiple systems atrophy (MSA), drug induced-parkinsonism, dystonic tremor or essential tremor will not be recruited.
 Known abnormality on CT or MRI brain imaging considered likely to compromise compliance with trial protocol/31P-MRS acquisition
 Known claustrophobia or other reasons why patient could not tolerate or be suitable for
31P-MRS
 Current or previous exposure to UDCA
 Current or previous diagnosis of liver disease, in particular PBC judged to be significant by the clinical investigator.
 Prior intracerebral surgical intervention for PD (including deep-brain stimulation). Patients who have previously undergone deep brain stimulation, intracerebral administration of growth factors, gene therapies or cell therapies will not be eligible.
 Already actively participating in a trial of a device, drug or surgical treatment for PD
 History of alcoholism
 Women of child-bearing potential (WOCBP)
 Participants who lack the capacity to give informed consent
 Any medical or psychiatric condition which in the investigator’s opinion compromises the potential participant’s ability to participate
 Concurrent dementia defined by a score lower than 25 on the Montreal Cognitive assessment (MoCA). Dementia may affect the ability of potential research participants to give informed consent or follow the study protocol.
 Concurrent severe depression defined by a score > 16 on the Montgomery-Asberg Depression Rating Scale (MADRS)
 Serum transaminases more than 2 times upper
limit of normal
 PD patients who are on ciclosporin, nitrendipine or dapsone for the treatment of concomitant, general medical conditions

E.5 End points

E.5.1

Primary end point(s)

The safety and tolerability of UDCA in Parkinson’s disease (PD) at a dose of 30 mg/kg

Metric:
• Number of serious adverse events (SAE)

• Number of adverse treatment reactions

• Number of patients completing the study

E.5.1.1

Timepoint(s) of evaluation of this end point

Each of the metrics below will be assessed over the whole study period (start of treatment to week 56) and summarised by treatment group.

E.5.2

Secondary end point(s)

• Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-
UPDRS) part 3 motor subsection Off medication score

• In vivo parameter estimates of high and low energy metabolite levels (ATP, PCr, Pi) , derived from cranial 31P-MRS centred on the basal ganglia and related motor regions

• Objective quantification of spatio-temporal gait parameters (optogait 5m), postural stability (Opals) and continuous activity monitory (McRoberts)

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline, week 48

For each of the secondary outcomes the change from baseline will be summarised within treatment groups using standard summary statistics (n, mean, standard deviation, median, minimum and maximum). The change from baseline will then be compared between treatment groups using a t-test. If there is an imbalance in baseline characteristics between randomised groups further analysis will be explored within the constraints of the small sample size, this may include an analysis of covariance. Scores will be suitably transformed if necessary. If the distributional assumptions for a t-test are not fulfilled an alternative analysis will be performed.

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

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)

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

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

Yes

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 end of the trial will be defined as the date of the last visit last subject. The regulatory authorities will be notified within 90 days of trial completion.

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