Clinical trial NCT01228396: AIMSPRO in the Treatment of Bladder Dysfunction in Secondary Progressive Multiple Sclerosis
Official title: A Randomised, Double-blind, Placebo-controlled Study of AIMSPRO in Treating Bladder Dysfunction in Secondary Progressive Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Secondary Progressive Multiple Sclerosis
Keywords: bladder
optic neuritis
secondary progressive multiple sclerosis
AIMSPRO
hyperimmune caprine serum
hyperimmune goat serum
Lead sponsor: Daval International Limited
Sponsor class: INDUSTRY
First posted: 2010-10-26
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Patients with marked bladder dysfunction as a result of secondary progressive multiple sclerosis are being recruited to receive AIMSPRO or placebo by subcutaneous injection, in this double-blind crossover study.

Detailed description: Treatment periods of 4 weeks' duration are separated by a 6 week wash-out phase. After 14 weeks of randomised therapy there is a 38 week period of "open-label" AIMSPRO treatment.

Eligibility criteria: Inclusion Criteria:

* M / F aged 18 years or older.
* Patients of childbearing potential must use adequate birth control measures for the duration of the study and 6 months after receiving the last injection of AIMSPRO.
* Clinically definite SPMS.
* Ambulant, walking aids allowed.
* No more than one relapse within the last 12 months and no relapse within the last 6 months.
* Urinary frequency of at least 8 times per 24-hours.
* Urinary urgency with or without urge incontinence.
* MRI brain or spinal cord abnormalities consistent with MS.
* 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
* Baseline AST , alkaline phosphatase, Thyroid function, Serum Electrophoresis levels must be within the normal range.
* Able to adhere to the study visit schedule and other protocol requirements
* Capable of giving written informed consent.

Exclusion Criteria:

* Acute symptomatic urinary infection.
* Taking DDAVP or antimuscarinic agents.
* Full time wheelchair user.
* Immunosuppressant drug therapy of any kind in the last 3 months.
* Relapse within the last 6 months.
* No clear progression of disability in the last 12 months.
* Co-existent medical condition precluding participation, including any history of severe allergic reaction.
* Pregnant or lactating women and women who are planning pregnancy within 12 months of screening (i.e., approximately 6 months following last injection).
* Receipt of any investigational drug within 30 days prior to screening or within 5 half-lives of the investigational agent, whichever is longer.
* Treatment with any therapeutic agent targeted at reducing TNF (e.g., infliximab, pentoxifylline, thalidomide, etanercept, etc.) within 3 months of screening.
* Previous administration of AIMSPRO.
* Ongoing corticosteroid therapy or any corticosteroids within the previous 3 months.
* History of known allergy to animal proteins, tuberculosis.
* 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.
* Patients with opportunistic infections within the previous 6 months.
* Established malignant disease, renal, hepatic, haematologic, gastrointestinal, endocrine, pulmonary, or cardiac disease.
* Significant other neurological disorder.
* Presence of a transplanted organ, with the exception of a corneal transplant \> 3 months prior to screening.
* 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.
* Recent clinically significant substance abuse (drug or alcohol).
* Poor tolerability of venipuncture.
* Investigational drugs or drugs targeted at reducing TNF are not allowed during participation in the study.
* 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.
* Immunosuppressive therapy within the month prior to entry into the study.
* Taking the licensed anticonvulsant medication lamotrigine or the anti-arrhythmic drug flecainide, both of which are potent sodium channel blocking agents.
* Unable to fill in the criteria related to bladder dysfunction status.
* Unable to give written informed consent.
* Use of intermittent or indwelling urinary catheter.

Primary outcomes:
measure: Change in average voided volume
timeFrame: At 0, 4, 10 and 14 weeks
Secondary outcomes:
measure: Change in average 24-hour frequency
timeFrame: At 0, 4, 10 and 14 weeks
measure: Change in visual acuity and colour vision
timeFrame: At 0, 4, 10 and 14 weeks
measure: Change in average 24-hour incontinence
timeFrame: At 0, 4, 10 and 14 weeks
measure: Change in urgency score
timeFrame: At 0, 4, 10 and 14 weeks
measure: Change in I-QOL score
timeFrame: At 0, 4, 10 and 14 weeks
measure: Change in Whittington Urgency Score
timeFrame: At 0, 4, 10 and 14 weeks
measure: Change in Kurtzke EDS
timeFrame: At 0, 4, 10 and 14 weeks
measure: Change in MSIS-29
timeFrame: At 0, 4, 10 and 14 weeks
measure: Change in MS FC
timeFrame: At 0, 4, 10 and 14 weeks
measure: Change in MS WS
timeFrame: At 0, 4, 10 and 14 weeks
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Free Hospital Hampstead NHS Trust
Study officials:
affiliation: University College, London
name: James Malone-Lee, MD
role: PRINCIPAL_INVESTIGATOR
References: