Development Status
Human Studies
AIMSPRO has been studied over several years in a number of Daval sponsored and Investigator Initiated clinical trials as well as open label observational studies. These include a long-term six-year study on a patient with Amyotrophic Lateral Sclerosis (ALS - the most common form of Motor Neuron Disease – also known as Lou Gehrig’s Disease), studies in Primary and Secondary Progressive Multiple Sclerosis (including optic neuritis, bladder instability) and Established Late Stage Diffuse Cutaneous Systemic Sclerosis.
Scleroderma Phase IIa Study
In 2005, a patient with advanced systemic sclerosis was treated with AIMSPRO on a compassionate basis. She then experienced a sustained improvement in mobility and, in particular, there was an improvement in proximal muscle power and skin characteristics. This positive clinical response led to the initiation of a Phase IIa human therapeutic clinical study of AIMSPRO in Established Diffuse Cutaneous Systemic Sclerosis, that was conducted at the Royal Free Hospital, London, U.K. Comprehensive details of this study can be viewed at:
http://clinicaltrials.gov/ct2/show/NCT00769028
In this study, 20 patients received either AIMSPRO or placebo, 1.0ml subcutaneously, twice weekly for 26 weeks. Standard outcome measures and novel biomarkers were used to investigate safety, efficacy and response to treatment. The study has enrolled and dosed all 20 required patients and all subjects have completed the initial 6 month double-blind placebo controlled phase. This randomised clinical trial was recently the subject of a successfully completed routine GCP audit by the MHRA.
The outcome measures for the trial are:
Primary Outcome Measures:
Safety and tolerability [Time Frame: Baseline, Week 6 and Week 26]
Modified Rodnan Skin Score [Time Frame: Baseline, Week 6 and Week 26]
Secondary Outcome Measures:
Scleroderma Health Assessment Questionnaire [Time Frame: Baseline, Week
6 and Week 26]
Scleroderma UK Functional Score [Time Frame: Baseline, Week 6 and Week 26]
Patient and Physician Global Assessment (VAS) [Time Frame: Baseline, Week 6 and Week 26]
SF-36 (Short form 36) [Time Frame: Baseline, Week 6 and Week 26]
MRC Sum Score [Time Frame: Week 0, Week 6 and Week 26]
Top Line Results
For the two Primary Endpoint Measures, safety and tolerability and the Modified Rodnan Skin Score, AIMSPRO met both of these primary endpoints. AIMSPRO was found to be a safe and well-tolerated medication when used in patients with established late stage diffuse systemic sclerosis at a dose of 1 ml given as a twice-weekly subcutaneous injection for 26 weeks. There was no deterioration in haematological, biochemical, cardiologic or in pulmonary parameters that were measured and no increase in adverse or serious adverse events were noted compared to placebo controls.
Furthermore, AIMSPRO exhibited a strong signal with the ability to arrest the deterioration in the MRSS when compared to placebo at 26 weeks (in the order of 27.1%), which is clinically significant (duration of illness dependent). It should be noted that patients within the trial had disease durations ranging from 10 to 30 years. Those patients with disease in the order of 10-15 years all improved in their MRSS more significantly on AIMSPRO.
For the secondary endpoint measures AIMSPRO exhibited a near statistically significant improvement in both the FEV1 & FVC compared to the placebo group at 26 weeks, thereby rescuing in effect the deterioration in lung function secondary to interstitial lung disease. Importantly no change in TLC or DLCO were noted. Finally, the patients SF-36 scores showed a strong signal with improvement of all eight of the individual scores assessed. The average increase was in the order of 41.6%. The difference in the overall SF-36 score was statistically significant between the AIMSPRO & placebo treated groups at 26 weeks (mean difference 41.61%).
Multiple Sclerosis Bladder Instability Phase II Study
A second randomised, placebo-controlled, double blind clinical trial, a Phase II human therapeutic study in patients with bladder instability in Secondary Progressive Multiple Sclerosis, has also been completed at the Royal Free Hospital. It was observed in previous open label studies that bladder function in Secondary Progressive Multiple Sclerosis was improved by treatment with AIMSPRO. In this study, 20 patients are participating in a crossover trial comparing AIMSPRO with a placebo. Subjects in both the placebo and treatment groups of the trial were given the treatment by subcutaneous injection twice weekly for 4 weeks. After a 6 week wash-out period they crossed over to receive 4 weeks of AIMSPRO or placebo. Further information about this study can be viewed at:
http://clinicaltrials.gov/ct2/show/NCT01228396
The trial is now complete and the data is being analysed and scrutinised very thoroughly and will be released presently.
Open Label Studies
Following significant clinical responses in certain conditions from the “named patient/compassionate use” administrations, approaches have been made to Daval from key opinion leaders in Australia, Europe, the United States and South America, to undertake ethically approved open label studies including:
- Amyotrophic Lateral Sclerosis (a form of Motor Neuron Disease)
- Optic Neuritis
- CIDP (Chronic Inflammatory Demyelinating Polyneuropathy)
- Guillain-Barré Syndrome
- Certain Cancers (prostate, breast, colon, pancreatic, skin, mesothelioma and endometrial)
- Inflammatory Bowel Disease
- HIV
- Hepatitis C
- Rheumatoid Arthritis
- Venous and Diabetic Ulceration /Wound Healing
- Burns
- Myasthenia Gravis
- Lupus
- Psoriatic Arthritis
- Ankylosing Spondylitis
- Juvenile Arthritis
- Adhesive Arachnoiditis
- Neuropathic pain
Daval intends to support these studies by provision of product. In addition, the respiratory function data in Amyotrophic Lateral Sclerosis, collected in a single patient over a period of ten years, are of such potential significance that an international, multi-centre study of AIMSPRO as a treatment of this condition is being prioritised. Daval’s Scientific Advisory Committee is currently in the process of outlining a synopsis and Protocol for such a study.
Further Animal Model Research
Supporting the clinical programme in humans, laboratory based research programmes have been undertaken at leading research establishments and Universities in the United Kingdom, France, the United States and Australia. Now that AIMSPRO has matured into its “finished” status, Daval has found greater efficiency in out-sourcing its research activities to internationally recognised authorities, to conduct further studies using genetically engineered animal models in order to extend the Intellectual Property base and to elucidate the complex Mechanism of Action and therapeutic potentials of AIMSPRO.