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

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ClinicalTrials.gov Identifier: NCT03039673
Recruitment Status : Recruiting
First Posted : February 1, 2017
Last Update Posted : January 11, 2019
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nīmes

Tracking Information
First Submitted Date  ICMJE January 31, 2017
First Posted Date  ICMJE February 1, 2017
Last Update Posted Date January 11, 2019
Actual Study Start Date  ICMJE June 19, 2017
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 31, 2017)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03039673 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MIROCALS: Modifying Immune Response and OutComes in ALS
Official Title  ICMJE 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
Brief Summary

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.

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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Amyotrophic Lateral Sclerosis
Intervention  ICMJE
  • 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
  • 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.

Study Arms  ICMJE
  • 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

    Interventions:
    • Drug: Riluzole
    • Drug: IL-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

    Interventions:
    • Drug: Riluzole
    • Drug: 5% glucose water solution
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 31, 2017)
216
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Gilbert Bensimon, MD, PhD 33142161669 gilbert.bensimon@psl.aphp.fr
Contact: Christine Payan, MD 33142161667 christine.payan@psl.aphp.fr
Listed Location Countries  ICMJE France,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03039673
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party Centre Hospitalier Universitaire de Nīmes
Study Sponsor  ICMJE Centre Hospitalier Universitaire de Nīmes
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Nigel Leigh, MD, PhD Brighton and Sussex Medical School
Study Director: Gilbert Bensimon, MD, PhD Centre Hospitalier Universitaire de Nîmes
PRS Account Centre Hospitalier Universitaire de Nīmes
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP