MIROCALS: Modifying Immune Response and OutComes in ALS (MIROCALS)
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| ClinicalTrials.gov Identifier: NCT03039673 |
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Recruitment Status :
Completed
First Posted : February 1, 2017
Last Update Posted : April 11, 2022
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MIROCALS is a phase II study of ld-IL-2 as a therapeutic agent for ALS. A randomized (1:1), placebo-controlled, double-blind, parallel group trial will be carried out to assess ld-IL-2 safety and clinical efficacy on survival and functional decline in newly diagnosed ALS patients treated for 18 months. Randomization will be stratified according to (i) country (n = 2 levels: UK, France) and (ii) site of onset (n= 2 levels: bulbar vs limb onset).
The primary objective to evaluate the clinical efficacy and safety of the experimental drug (ld IL-2) over an 18 months period in order to establish the proof of concept (PoC) that modifying immune responses through the enhancement of regulatory T cells modifies the rate of ALS disease progression.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Amyotrophic Lateral Sclerosis | Drug: Riluzole Drug: IL-2 Drug: 5% glucose water solution | Phase 2 |
The secondary objectives of MIROCALS are:
To validate a new phase-II study design to improve the efficiency of drug development in ALS with early determination of drug response using established biomarkers (BMs).
The aims of this new trial design are:
(i) To shorten future trials duration in ALS using an early drug responding surrogate marker of disease activity; (ii) To establish the proof of mechanism (PoM) of the tested drugs; (iii) To identify drug responder status.
Additional exploratory objectives are:
(i) Deep immune & inflammatory phenotyping (ii) Brain biomarkers (iii) Genomics and Transcriptomics
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 304 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official 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 |
| Actual Study Start Date : | June 19, 2017 |
| Actual Primary Completion Date : | July 22, 2021 |
| Actual Study Completion Date : | July 22, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: low dose interleukin-2
Patients randomized to this arm will receive subcutaneous injections of low-dose interleukin-2 in addition to oral Riluzole treatment. Intervention: Riluzole Intervention: IL-2 |
Drug: Riluzole
All patients will be treated with Riluzole for a period of three months prior to final inclusion and randomization. Riluzole treatment will continue throughout the 18 months of follow-up planned for in this protocol. Riluzole treatment is part of routine care for patients with ALS. Drug: IL-2 The dose of IL-2 to be used in this study will be 2.0 million IU/day. Each treatment course will last 5 days (i.e. 1 sub-cutaneous injection per day for 5 consecutive days). The 5-day course will be repeated every 4-weeks over an 18-month treatment period. In case of intolerance, a flexible dose-reduction schedule is available. Other Names:
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Placebo Comparator: Placebo
Patients randomized to this arm will receive subcutaneious placebo injections (5% glucose water solution) in addition to oral Riluzole treatment. Intervention: Riluzole Intervention: 5% glucose water solution |
Drug: Riluzole
All patients will be treated with Riluzole for a period of three months prior to final inclusion and randomization. Riluzole treatment will continue throughout the 18 months of follow-up planned for in this protocol. Riluzole treatment is part of routine care for patients with ALS. Drug: 5% glucose water solution The placebo consists of 5% glucose water solution, which is the matrix with which low-dose IL-2 injections are prepared in the experimental arm. Placebo injections are prepared in exactly the same manner as IL-2 injections, just without the IL-2. Each treatment course will last 5 days (i.e. 1 sub-cutaneous injection per day for 5 consecutive days). The 5-day course will be repeated every 4-weeks over an 18-month treatment period. |
- Time to death from date of randomization to date of death [ Time Frame: Month 21 ]Time to death from date of randomization to date of death as documented in death certificates, or date of last documented news for patients lost to follow-up, or 640 days for patients who survive more than 640 days (censoring at 640 days). Death certificates are collected by the centre's principal investigator from the City Hall of the patients' home or birth place.
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| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Main 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
Main 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03039673
Show 17 study locations
| Principal Investigator: | Nigel Leigh, MD, PhD | Brighton and Sussex Medical School | |
| Study Director: | Gilbert Bensimon, MD, PhD | Centre Hospitalier Universitaire de Nîmes |
| Responsible Party: | Centre Hospitalier Universitaire de Nīmes |
| ClinicalTrials.gov Identifier: | NCT03039673 |
| Other Study ID Numbers: |
H2020/PHRC-N/2014/GB-01 No 633413 ( Other Grant/Funding Number: EU Horizon 2020 research and innovation programme ) PHRC-N, 14-0077, 2014 ( Other Grant/Funding Number: the French Ministry of Health ) Leigh/Jul15/971-797 ( Other Grant/Funding Number: MND Association grant ) |
| First Posted: | February 1, 2017 Key Record Dates |
| Last Update Posted: | April 11, 2022 |
| Last Verified: | April 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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interleukin-2 low-dose interleukin-2 |
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Motor Neuron Disease Amyotrophic Lateral Sclerosis Sclerosis Pathologic Processes Neurodegenerative Diseases Nervous System Diseases Neuromuscular Diseases Spinal Cord Diseases Central Nervous System Diseases TDP-43 Proteinopathies Proteostasis Deficiencies Metabolic Diseases Interleukin-2 Riluzole |
Antineoplastic Agents Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anticonvulsants Excitatory Amino Acid Antagonists Excitatory Amino Acid Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Neuroprotective Agents Protective Agents |