Clinical Trials Register

Summary
EudraCT Number:	2018-003028-35
Sponsor's Protocol Code Number:	CTU/2016/278
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:	2019-11-15
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

2018-003028-35

A.3

Full title of the trial

A randomised, double blind, parallel group, placebo controlled, Phase 3 trial of exenatide once weekly over 2 years as a potential disease modifying treatment for Parkinson's disease.

A.3.1

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

A randomised, double blind, parallel group, placebo controlled, Phase 3 trial of exenatide once weekly over 2 years as a potential disease modifying treatment for Parkinson's disease.

A.3.2

Name or abbreviated title of the trial where available

Phase 3 Trial of exenatide for Parkinson’s disease

A.4.1

Sponsor's protocol code number

CTU/2016/278

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN14552789

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04232969

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	University College London Comprehensive Clinical Trial Unit
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	National Institute for Health Research -Efficacy and Mechanism Evaluation Programme
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 College London Comprehensive Clinical Trials Unit
B.5.2	Functional name of contact point	Chief Investigator
B.5.3	Address:
B.5.3.1	Street Address	UCL Queen Square Institute of Neurology, 33 Queen Square
B.5.3.2	Town/ city	London
B.5.3.3	Post code	WC1N 3BG
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	02034488726
B.5.6	E-mail	t.foltynie@ucl.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	Bydureon
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca
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	Bydureon
D.3.4	Pharmaceutical form	Powder and solvent for prolonged-release suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Exenatide
D.3.9.1	CAS number	141732-76-5
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	2
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	Powder and solvent for prolonged-release suspension for injection
D.8.4	Route of administration of the placebo	Subcutaneous 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

E.1.1.1

Medical condition in easily understood language

Parkinson's disease

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	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10013113
E.1.2	Term	Disease Parkinson's
E.1.2	System Organ Class	100000004852

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 current trial objective is to confirm whether the previous positive results seen with exenatide in Parkinson's disease can be reproduced in a multi-centre trial design, including a larger number of patients evaluated over twice as long a period. This will be achieved by comparing the effectiveness of exenatide once weekly versus placebo on the MDS-UPDRS part 3 motor sub-score in the “practically defined OFF medication state” in patients with mild-moderate severity PD. (Change in the MDS-UPDRS part 3 score reflects accumulation of motor deficit and therefore is a measure of PD motor progression.) The hypothesis is that exenatide will be associated with reduced MDS-UPDRS part 3 scores at the 96 week time-point.

E.2.2

Secondary objectives of the trial

An important secondary objective is to explore whether any positive effects seen after 48 weeks exenatide exposure remain static or increase in amplitude by the 96 week time point.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

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

Genetics Sub-Study(optional) - has the aim of trying to identify genetic markers that may be associated with sub-types of PD or variation in treatment responsiveness. The primary aim of this resource and of future work will be to enable targeting of the best treatments to specific patient groups.

Cerebrospinal Fluid Sub-Study (optional) - has the aim to determine whether any CSF changes associated with PD are influenced by exposure to exenatide. These may include alpha synuclein monomers or oligomers, Neuroinflammatory markers, Exosomal contents.

Remote Monitoring of PD symptoms Sub-Study (optional) - has the aim to help determine whether the longitudinal assessment of voice and movement symptoms in patients with PD is better performed using smartphone technology or by conventional methods administered by a doctor or nurse.

DaTSCAN Imaging Sub Study (optional)- to determine if change in dopamine transporter availability in the caudate and putaminal nuclei as measured by quantitative DaTSCAN signal is influenced by exposure to exenatide.

E.3

Principal inclusion criteria

1. Diagnosis of Parkinson’s disease. PD is a clinical diagnosis and is based on the opinion of the PI or delegate on site after review of the clinical history, examination findings and response to PD medication. The Queen Square brain bank criteria MAY be used to help assist in the diagnosis, although this need not be a formal inclusion criteria, and the relevance of a positive family history of PD, or a confirmed genetic basis for an individual’s symptoms will be evaluated in the context of other clinical features in determining diagnosis and eligibility.
2. Hoehn and Yahr stage ≤2.5 in the ON medication state. This implies that all patients will be mobile without assistance during their best “ON” medication periods.
3. Between 25 and 80 years of age.
4. On dopaminergic treatment for at least 4 weeks before enrolment. All participants must have had previous or ongoing exposure to dopaminergic treatment either as L-dopa or a dopamine agonist. If L-dopa has been stopped due to side effects or lack of response, the local PI should further confirm that the participant has clinical symptoms and signs and/or radiological investigations consistent with a diagnosis of Parkinson’s disease.
5. Ability to self-administer, or to arrange carer administration of trial medication.
6. Documented informed consent to participate.

E.4

Principal exclusion criteria

1. Diagnosis or suspicion of other cause for Parkinsonism. Patients with clinical features indicating a diagnosis of Progressive Supranuclear Palsy, Multiple Systems Atrophy, Drug induced Parkinsonism, Dystonic tremor or Essential tremor will not be recruited.
2. Patients unable to attend the clinic visits in the practically defined OFF medication state.
3. Body mass index <18.5. (Exenatide is known to cause weight loss therefore individuals that may not tolerate further weight loss will not be recruited).
4. Known abnormality on CT or MRI brain imaging considered likely to compromise compliance with trial protocol.
5. Significant cognitive impairment defined by a score <21 on the Montreal Cognitive Assessment.
6. Concurrent severe depression defined by a score ≥16 on the Patient Health Questionnaire (PHQ-9).
7. Prior intra-cerebral surgical intervention for Parkinson’s disease. Patients who have previously undergone Deep Brain Stimulation, intra-cerebral administration of growth factors, gene therapy or cell therapies will not be eligible.
8. Previous participation in one of the following Parkinson’s disease trials (Biogen SPARK trial, Prothena Pasadena trial, Sanofi Genzyme MOVES-PD trial, UDCA-PD UP Study or any other trial still considered to involve a potentially PD modifying agent).
9. Participation in another clinical trial of a device, drug or surgical treatment within the last 30 days.
10. Previous exposure to exenatide.
11. Impaired renal function with creatinine clearance <50ml/min.
12. History of pancreatitis. Screening serum amylase value must fall within laboratory normal range +/- 50%.
13. Type 1 or Type 2 Diabetes mellitus.
14. Severe gastrointestinal disease (e.g. gastroparesis)
15. Hyperlipidaemia. A lipid profile will be tested at the screening visit. Cholesterol or Triglyceride levels greater than 2 x the upper limit of normal will raise suspicion of a familial or acquired hyperlipidaemia and will prompt referral to a relevant specialist for investigation and treatment.
16. History or family history of medullary thyroid cancer (MTC). Undiagnosed neck lump, hoarse voice or difficulty swallowing (not attributable to PD diagnosis).
17. Multiple endocrine neoplasia 2 (MEN2) syndrome.
18. Hypersensitivity to any of exenatide's excipients.
19. Females that are pregnant or breast feeding. There are no safety data regarding Exenatide use in pregnancy.
20. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire trial period and up to 3 months after the last dose of trial medication. Female participants who are able to become pregnant (defined as women of child bearing potential) will undergo a pregnancy test prior to randomisation and will be asked at each visit to confirm regular use of an effective method of contraception.
21. Participants who lack the capacity to give informed consent.
22. Any medical or psychiatric condition or previous conventional/experimental treatment which in the investigator’s opinion compromises the potential participant’s ability to participate.

E.5 End points

E.5.1

Primary end point(s)

Comparison of MDS-UPDRS part 3 motor sub-score in the practically defined OFF medication state at 96 weeks between participants according to treatment allocation.

E.5.1.1

Timepoint(s) of evaluation of this end point

96 weeks

E.5.2

Secondary end point(s)

Difference between 96 week scores for each of the secondary outcomes listed below will be compared between groups according to treatment allocation:
• Movement Disorder Society Unified Parkinson’s Disease Rating Scale part 1,2,3 and 4 ON medication scores
• Montreal Cognitive Assessment
• Safety and tolerability of Exenatide as indicated by changes in vital signs, weight, clinical laboratory measures and adverse events
• Beck Depression Inventory
• Unified Dyskinesia Rating Scale
• Parkinson’s Disease 39 item Quality of life questionnaire
• Non-Motor Symptoms scale
• Levodopa equivalent doses
• 3 Day Hauser Diary

Difference between 48 and between 48 to 96 week scores for each of the secondary outcomes listed below will be compared between groups according to treatment allocation
• Movement Disorder Society Unified Parkinson’s Disease Rating Scale part 3 Motor subsection OFF medication score
• Movement Disorder Society Unified Parkinson’s Disease Rating Scale part 1,2,3 and 4 ON medication scores

E.5.2.1

Timepoint(s) of evaluation of this end point

48 and 96 weeks

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

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

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 for individual participants will be the date of their last visit. Trial closure is defined as the date when all data has been received, cleaned and all queries resolved at all sites.

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