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

• ClinicalTrials.gov Identifier: NCT03039673
• Recruitment Status: Active, not recruiting
• First Posted: February 1, 2017
• Last Update Posted: January 29, 2021
• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Information provided by (Responsible Party): Centre Hospitalier Universitaire de Nīmes

Tracking Information

• First Submitted Date: January 31, 2017
• First Posted Date: February 1, 2017
• Last Update Posted Date: January 29, 2021
• Actual Study Start Date: June 19, 2017
• Estimated Primary Completion Date: September 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: MIROCALS: Modifying Immune Response and OutComes in ALS
• 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

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

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 31, 2019): 304
• Original Estimated Enrollment (submitted: January 31, 2017): 216
• Estimated Study Completion Date: September 2021
• Estimated Primary Completion Date: September 2021 (Final data collection date for primary outcome measure)

Eligibility 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)
• History of documented symptomatic and treated asthma within the past 5 years

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, United Kingdom

Administrative Information

• NCT Number: 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 )
• 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

• Plan to Share IPD: Yes

• Responsible Party: Centre Hospitalier Universitaire de Nīmes
• Study Sponsor: Centre Hospitalier Universitaire de Nīmes
• Collaborators: Not Provided

Investigators

• 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 2020