E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064060 |
E.1.2 | Term | Multiple system atrophy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 Unified 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. |
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E.2.2 | Secondary objectives of the trial |
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 Unified 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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the difference in total Unified Multiple System Atrophy Rating Scale (UMSARS) score (Parts I and II) at 48 weeks comparing exenatide to best medically treated patients. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 Unified 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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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The expected duration of the trial is 3 years from recruitment of the first participant. The end of the trial is the date of the last follow up of the last participant. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |