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MIROCALS: Modifying Immune Response and OutComes in ALS (MIROCALS)

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by Centre Hospitalier Universitaire de Nīmes
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nīmes
ClinicalTrials.gov Identifier:
NCT03039673
First received: January 31, 2017
Last updated: June 20, 2017
Last verified: June 2017
  Purpose

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 Intervention Phase
Amyotrophic Lateral Sclerosis Drug: Riluzole Drug: IL-2 Drug: 5% glucose water solution Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Nīmes:

Primary Outcome Measures:
  • Time to death from date of randomization to date of death [ Time Frame: Month 18 ]
    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 548 days for patients who survive more than 548 days (censoring at 548 days). Death certificates are collected by the centre's principal investigator from the City Hall of the patients' home or birth place.


Estimated Enrollment: 216
Actual Study Start Date: June 19, 2017
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • low dose interleukin-2
  • ultra low dose interleukin-2
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.


Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03039673

Contacts
Contact: Gilbert Bensimon, MD, PhD gilbert.bensimon@psl.aphp.fr
Contact: Christine Payan, MD christine.payan@psl.aphp.fr

Locations
France
CHRU de Lille - Hôpital Roger Salengro Not yet recruiting
Lille, France, 59037
Principal Investigator: Dr Véronique Danel, MD, PhD         
CHU de Limoges - Hôpital Dupuytren Recruiting
Limoges, France, 87042
Principal Investigator: Philippe Couratier, MD, PhD         
HCL - Hôpital Neurologique P. Wertheimer Recruiting
Lyon, France, 69677
Principal Investigator: Dr Emilien Bernard, MD, PhD         
APHM - Hôpital de la Timone Not yet recruiting
Marseille, France, 13385
Principal Investigator: P Shahram Attarian, MD, PHD         
CHRU de Montpellier - Hôpital Gui de Chauliac Recruiting
Montpellier Cedex 5, France, 34295
Principal Investigator: William Camu, MD, PhD         
CHU de Nice - Hôpital Pasteur Not yet recruiting
Nice, France, 06002
Principal Investigator: Claude Desnuelle, MD, PhD         
APHP - Groupe Hospitalier Pitié-Salpetrière Recruiting
Paris Cedex 13, France, 75651
Principal Investigator: François Salachas, MD         
CHRU de Tours - Hôpital Bretonneau Recruiting
Tours, France, 37044
Principal Investigator: Philippe Corcia, MD, PhD         
United Kingdom
Trafford Centre for Biomedical Research Recruiting
Brighton, United Kingdom, BN1 9RY
Principal Investigator: P Nigel Leigh, MD, PhD         
North-East London and Essex MND Regional Care Centre Not yet recruiting
London, United Kingdom, E1 4NS
Principal Investigator: Andrea Malaspina, MD, PhD         
King's MND Care and Research Centre Not yet recruiting
London, United Kingdom, SE5 8AF
Principal Investigator: Ammar Al-Chalabi, MD, PhD         
Centre for Neuromuscular Diseases - National Hospital of Neurology Not yet recruiting
London, United Kingdom, WC1N 3BG
Principal Investigator: Dr Nikhil SHARMA, MD, PhD         
Sheffield Care and Research Centre Not yet recruiting
Sheffield, United Kingdom, S10 2JF
Principal Investigator: Pamela J Shaw, MD, PhD         
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nīmes
Investigators
Principal Investigator: Nigel Leigh, MD, PhD Brighton and Sussex Medical School
Study Director: Gilbert Bensimon, MD, PhD Centre Hospitalier Universitaire de Nîmes
  More Information

Responsible Party: Centre Hospitalier Universitaire de Nīmes
ClinicalTrials.gov Identifier: NCT03039673     History of Changes
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 )
Study First Received: January 31, 2017
Last Updated: June 20, 2017
Individual Participant Data  
Plan to Share IPD: Yes

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Centre Hospitalier Universitaire de Nīmes:
interleukin-2
low-dose interleukin-2

Additional relevant MeSH terms:
Sclerosis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Pharmaceutical Solutions
Riluzole
Interleukin-2
Anticonvulsants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents
Antineoplastic Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on June 28, 2017