|Study title||Efficacy and safety of low-dose IL-2 (ld-IL-2) as a Treg enhancer for controlling neuro-inflammation in newly diagnosed Amyotrophic Lateral Sclerosis (ALS) patients: A randomized, double-blind, placebo- controlled, phase-II Proof of Concept/ Proof of Mechanism Clinical Trial|
|UK Chief Investigator||Professor Nigel Leigh|
|Research summary||Amyotrophic Lateral Sclerosis (ALS) is a devastating, disabling and rare disease which progressively breaks down and damages the nerve cells in the brain and spine. It affects approx 50,000 people in the EU at any time and approx 10,000 deaths each year. Some interventions are provided to manage the symptoms of this disease, but care is largely supportive and palliative. The cost to society and to individuals is significant; much of it is health care costs. There is a pressing need to find disease-modifying therapies that will slow disease progression, increase survival and better quality of life.
Riluzole is still the only agent shown to modify survival in ALS but its affects are modest. This tells us that modifying disease progression is a realistic goal in ALS.
Research has shown neuroinflammation significantly contributes to neuronal damage. It is thought if this neuroinflammation can be modified this targeted therapy would be very effective in ALS patients. Previous therapeutic attempts targeted the suppression of all immuno-inflammatory cells, but the risks of toxicity outweighed the benefits of drug effect.
Targeting specific regulatory T-cells called Tregs has shown to reduce neuroinflammation more safely and effectively and low dose IL-2 (ld-IL2) acts through these Tregs.
This study is a randomised, double-blind, placebo-controlled, parallel group, stratified study (country (UK vs France) and site of disease onset (limb vs bulbar)). Bulbar region is lower part of the skull. It investigates the efficacy & safety of low-dose IL2 therapy for 18 months as an add-on therapy with riluzole, and compares the efficacy and safety to riluzole plus placebo in recently diagnosed ALS patients.
The study will take place in 5 Hospitals in England (and 5 Hospitals in France) and will run for 36 months. They hope to recruit 72 patients in the UK from October 2016 (216 patients in total across France and UK).
|Inclusion/exclusion criteria||Key Inclusion Criteria:
- Patient is 18 years old and less than 76 years old
- Possible, Probable, Probable laboratory-supported or Definite ALS as defined by El Escorial Revised ALS diagnostic criteria
- Disease duration <= 24 months
- Slow Vital capacity >= 70% of normal
- No prior or present riluzole treatment
- Lumbar punctures accepted by patient and done
Key Exclusion Criteria:
- Other neurodegenerative disease that could explain signs or symptoms
- Contra indication for lumbar puncture (history of allergy to xylocaine, presence of contra-indicated treatment, or coagulation test abnormality, clinically significant coagulopathy or thrombocytopenia)
- Non authorized treatment
- Other disease or disorders that could preclude functional assessment, or life-threatening disorders
- Any documented, active, past or present, auto-immune disorders except asymptomatic Hashimoto thyroiditis
- Using assisted ventilation
- Feeding through gastrostomy or nasogastric tube
- Women of child-bearing potential or sexually active man without contraception
- Pregnant or breast feeding woman
- Any clinically significant laboratory abnormality (excepting cholesterol, triglyceride, glucose, CK, ferritin)
- History of documented symptomatic and treated asthma within the past 5 years.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
|Current status||Active – recruiting|
|Locations||Brighton Principal Investigator: P Nigel Leigh, MD, PhD
Sheffield Principal Investigator: Pamela J Shaw, MD, PhD
Glasgow Principal Investigator: George Gorrie, MD,PhD
Bart's Health NHS Trust, London Principal Investigator: Andrea Malaspina, MD, PhD
King's College Hospital, London Principal Investigator: Ammar Al-Chalabi, MD, PhD
National Hospital of Neurology & Neurosurgery, University College London Principal Investigator: Dr Nikhil SHARMA, MD, PhD
|Contact details||Coordinating centre:
Contact: Gilbert Bensimon, MD, PhD +33142161669 firstname.lastname@example.org
Contact: Christine Payan, MD +33142161667 email@example.com
|Recruitment group(s)||Patients with MND|
|Recruitment target(s)||UK target: approximately 80 patients enrolled, to reach 72 randomised patients.
Global target: 216 randomised patients.
|Key dates||Study start date: 19 June 2017 (global)
Target study completion date: June 2021
|Funder(s)||EU Horizon 2020 and the MND Association
|Sponsor||Centre Hospitalier Universitaire de Nīmes|
|Study design||Interventional (clinical trial)|
|Intervention (if applicable)||Drug: IL-2
Other: Placebo (5% glucose water solution)
|Phase (if applicable)||Phase 2|
|Outcome measures||Primary Outcome Measures: Time to death from date of randomization to date of death|
|Publications / Results reports|
|Participant Information Sheet|