E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Overactive Bladder in Secondary Progressive Multiple Sclerosis and the other neurological symptoms associated with Secondary Progressive Multiple Sclerosis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063400 |
E.1.2 | Term | Secondary progressive multiple sclerosis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059617 |
E.1.2 | Term | Overactive bladder |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012547 |
E.1.2 | Term | Detrusor hyperreflexia |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This is a proof of concept study. We seek to identify a signal that would justify further development of this drug, on the grounds of reasonable probability of true efficacy in the management of patients with multiple sclerosis (MS). To date, Some 400 patients with MS have now taken the medication for periods of up to 5 years. The most commonly reported benefit has been an improvement in bladder function, so it is judged that it would be best to conduct a proof of concept study on the overactive bladder symptoms associated with MS.
The primary outcome measure will be the change in average voided volume |
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E.2.2 | Secondary objectives of the trial |
The following secondary outcome measures will be studied Change in average 24-hour frequency of micturition Change in average 24-hour frequency of incontinence episodes Change in I-QOL score - An incontinence related quality of life measure Change in Whittington Urgency Score - A measure of the symptom of urinary urgency Change in Kurtzke Extended disability Scale Change in MSIS-29 - MS Impact scale Change in MS FC - Functional Composite Score Change in MS WS - Walking Scale Change in visual acuity and colour vision
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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 |
Eight patients, to be randomly selected from the overall trial cohort, will undergo threshold tracking studies to test open-label observations of a reduction of sodium channel triggering voltages following AIMSPRO administration |
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E.3 | Principal inclusion criteria |
Patients who meet all of the following criteria will be eligible for study enrolment
1. Male and Female patients aged 18 years or older. a. Men and women of childbearing potential must use adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) for the duration of the study and should continue such precautions for 6 months after receiving the last injection of AIMSPRO. 2. Have clinically definite SPMS. 3. Be ambulant, walking aids allowed. 4. Have had no more than one relapse within the last 12 months and no relapse within the last 6 months. 5. Urinary frequency of 8 times per 24-hours 6. Urinary urgency with or without urge incontinence 7. Have a record of MRI brain or spinal cord abnormalities consistent with the diagnosis of MS. 8. The screening laboratory test results must meet the following criteria: • Haemoglobin 9.5 g/dL • WBC 3.5 x 109/L • Neutrophils 1.5 x 109/L • Platelets 100 x 109/L 9. Baseline AST , alkaline phosphatase, Thyroid function, Serum Electrophoresis levels must be within the normal range for the laboratory conducting the test 10. Be able to adhere to the study visit schedule and other protocol requirements. 11. Capable of giving written informed consent. Consent must be obtained prior to any screening procedures.
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E.4 | Principal exclusion criteria |
If any of the following exclusion criteria are met, the patient is ineligible for the study:
1. Acute symptomatic urinary infection 2. Taking DDAVP for control of nocturia 3. Taking antimuscarinic agents for the control of overactive bladder symptoms 4. Full time wheelchair user. 5. History of immunosuppressant drug therapy of any kind in the last 3 months. 6. Relapse within the last 6 months. 7. No clear progression of disability in the last 12 months. 8. Co-existent medical condition precluding participation, including any history of severe allergic reaction. 9. Pregnant or lactating women and women who are planning pregnancy within 12 months of screening (i.e., approximately 6 months following last injection). 10. Receipt of any investigational drug within 30 days prior to screening or within 5 half-lives of the investigational agent, whichever is longer. 11. Treatment with any therapeutic agent targeted at reducing TNF (e.g., infliximab, pentoxifylline, thalidomide, etanercept, etc.) within 3 months of screening. 12. Previous administration of AIMSPRO. 13. Ongoing corticosteroid therapy or any corticosteroids within the previous 3 months. 14. History of known allergy to animal proteins. 15. Known history of tuberculosis. 16. Serious infections (such as pneumonia or pyelonephritis) in the previous 3 months. Less serious infections such as acute upper respiratory tract infection or simple urinary tract infection, should be followed to their conclusion or treated, as appropriate, prior to inclusion. 17. Patients with opportunistic infections, including but not limited to evidence of active cytomegalovirus, active Pneumocystis carinii, Aspergillosis, histoplasmosis or atypical mycobacterium infection, etc, within the previous 6 months. 18. Patients with established malignant disease, renal, hepatic, haematologic, gastrointestinal, endocrine, pulmonary, or cardiac disease. 19. Patients with a significant other neurological disorder. 20. Presence of a transplanted organ, with the exception of a corneal transplant > 3 months prior to screening. 21. History of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (such as nodes in the posterior triangle of the neck, infra-clavicular, epitrochlear, or periaortic areas), or splenomegaly. 22. Known recent clinically significant substance abuse (drug or alcohol). 23. Poor tolerability of venepuncture or lack of adequate venous access for required blood sampling during the study period. 24. Investigational drugs or drugs targeted at reducing TNF; infliximab, pentoxifylline, thalidomide, etanercept, or other agents are not allowed during participation in the study. 25. Patients will not be permitted to receive immunosuppressive treatment during this study. The exception will be where a patient’s treating neurologist determines that a course of steroid therapy, oral or intravenous, is required in view of a sufficiently disabling relapse of MS. 26. Have received immunosuppressive therapy within the month prior to entry into the study. 27. Taking the licensed anticonvulsant medication lamotrigine or the anti-arrhythmic drug flecainide, both of which are potent sodium channel blocking agents. 28. Unable to fill in the criteria related to bladder dysfunction status 29. Unable to give written informed consent
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in average voided volume |
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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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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 | Yes |
E.8.2.3 | Other | No |
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.8.5.1 | Number of sites anticipated in the EEA | 1 |
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 | Information not present in EudraCT |
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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(1) Last visit of the last subject undergoing the trial (2) The study shall be terminated if data collected from this study or other sources demonstrates that exposure to AIMSPRO is associated with unacceptable risks. This judgement will be exercised by the Principal Investigator |
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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 | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 6 |