Exenatide once-weekly as a treatment for Multiple System Atrophy.

• Register: EUCTR
• Last refreshed on: 8 June 2020
• Main ID: EUCTR2020-000122-26-GB
• Date of registration: 06/04/2020
• Prospective Registration: Yes
• Primary sponsor: University College London (UCL)
• Public title: Exenatide once-weekly as a treatment for Multiple System Atrophy.
• Scientific title: A Phase IIa, open label, single-site, 48 week randomised controlled trial evaluating the safety and efficacy of Exenatide once-weekly in the treatment of patients with Multiple System Atrophy - Exenatide once-weekly as a treatment for Multiple System Atrophy.
• Date of first enrolment: 11/05/2020
• Target sample size: 50
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-000122-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: Standard of Care; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: Misha Ladva Joint Research Office
• Affiliation: University College London (UCL)

• Name: Misha Ladva Joint Research Office
• Affiliation: University College London (UCL)

Key inclusion & exclusion criteria

Inclusion criteria:
Participants aged 30-80 years old with a diagnosis of Possible or Probable MSA of the parkinsonian subtype (MSA-P) or cerebellar subtype (MSA-C) according to The Gilman Criteria (Gilman et al. 2008).

Participants who are less than five years from the time of documented MSA diagnosis or from the time of documented parkinsonian / ataxic neurological condition that later turns out to be MSA.

Participants who are able to walk at least 10 metres with or without assistance. Participants with an anticipated survival of at least three years in the opinion of the investigator.

Participants that are willing to adhere to the study drug regimen.

Participants that are willing and able to perform all protocol-specified assessments and comply with the study visit schedule.

Females of childbearing potential and male participants with partners of childbearing potential must agree to use an effective method of contraception from the time consent is signed until 10 weeks after treatment discontinuation. Females of childbearing potential have a negative pregnancy test within 7 days prior to being randomised.

Willing and able to provide written informed consent.

Subjects who are not able to write may give verbal consent in the presence of at least one witness, and the witness should sign the informed consent form.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
Females who are pregnant, planning pregnancy or breastfeeding.

Women of child-bearing potential who do not practice an acceptable method of birth control.

Subjects who meet any of the following criteria which tend to suggest advance disease:
1. Speech impairment as assessed by a score of = 3 on UMSARS question 1
2. Swallowing impairment as assessed by a score of = 3 on UMSARS question 2
3. Impairment in ambulation as assessed by a score of = 3 on UMSARS question 7
4. Falling more frequently than once per week as assessed by a score of = 3 on UMSARS question 8.

Participants with a clinically significant or unstable medical or surgical condition, which in the opinion of the investigator might preclude safe completion of the study.

Participants with active malignant neoplasms or history of malignant neoplasm in the last 5 years.

Participants with movement disorders other than MSA.

Concurrent dementia defined by a score lower than 21 on the MoCA.

Concurrent severe depression defined by a score of =30 on the Beck Depression Inventory-II.

History of deep brain stimulation surgery.

Participants who have taken any investigational products within 90 days prior to baseline.

Participants with a BMI < 18.5.

Participants with diabetes, end stage renal disease or severely impaired renal function.

History of clinically significant cardiac disease, pancreatitis and/or alcoholism.

Participants with severe gastrointestinal disease including gastroparesis.

Ongoing treatment with sulphonylurea.

Known allergies to the IMP and excipients of IMP.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Multiple System Atrophy
MedDRA version: 21.1 Level: PT Classification code 10064060 Term: Multiple system atrophy System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: Bydureon
Product Name: Bydureon
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Exenatide
CAS Number: 141732-76-5
Current Sponsor code: EFC13794
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2mg in-0.65ml

Primary Outcome(s)

Main Objective: This is an open label, randomised trial to collect pilot data from which to estimate the effectiveness of Exenatide in modifying disease progression of patients with Multiple System Atrophy. The primary endpoint will be the difference in total Uni?ed Multiple System Atrophy Rating Scale (UMSARS-I) score (Parts I and II) at 48 weeks comparing exenatide to best medically treated patients.

The Unified MSA rating scale is globally recognised as the best available scale to objectively rate the severity of MSA. Part 1 (Historical review of symptom severity) and Part 2 (motor examination) have been previously used many times as an outcome measure in trials of MSA. Part 3 captures additional autonomic symptoms eg dizziness from low blood pressure, while Part 4 captures overall disability from the disease.

Timepoint(s) of evaluation of this end point: 48 weeks

Primary end point(s): The primary endpoint will be the difference in total Uni?ed Multiple System Atrophy Rating Scale (UMSARS) score (Parts I and II) at 48 weeks comparing exenatide to best medically treated patients.

Secondary Objective: This trial will also allow estimates of the impact exenatide on;

The proportion of patients with loss of independent ambulation by the end of the study, defined by a score of 3 or more in the Uni?ed Multiple System Atrophy Rating Scale (UMSARS) section I, item 7 (walking).

The difference at week 48 in the Multiple system atrophy- quality of life (MSA-QoL) scale.

The difference at week 48 in UMSARS parts III and IV.

The difference in anti-parkinsonian or anti-orthostatic hypotension drugs.

The total number of falls.

The proportion of patients reaching a score of 3 or more on UMSARS-I items 1 (speech), 2 (swallowing), and 8 (falling).

The difference at week 48 in clinical global impression (CGI); difference at week 48 in the Montreal cognitive assessment (MoCA) scores.

Secondary Outcome(s)

Secondary end point(s): The proportion of patients with loss of independent ambulation by the end of the study, defined by a score of 3 or more in the Uni?ed Multiple System Atrophy Rating Scale (UMSARS) section I, item 7 (walking).

The difference at week 48 in the Multiple system atrophy- quality of life (MSA-QoL) scale.

The difference at week 48 in UMSARS parts III and IV.

The difference in anti-parkinsonian or anti-orthostatic hypotension drugs.

The total number of falls.

The proportion of patients reaching a score of 3 or more on UMSARS-I items 1 (speech), 2 (swallowing), and 8 (falling).

The difference at week 48 in clinical global impression (CGI);

Difference at week 48 in the Montreal cognitive assessment (MoCA) scores.

Timepoint(s) of evaluation of this end point: 48 weeks

Secondary ID(s)

125591

Source(s) of Monetary Support

John Black Charitable Foundation

Van Andel Research Institute

Defeat MSA

Ethics review

Status: Approved
Approval date: 11/05/2020
Contact: