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

Primary Purpose

Amyotrophic Lateral Sclerosis

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Riluzole

IL-2

5% glucose water solution

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring interleukin-2, low-dose interleukin-2

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

CHRU de Lille - Hôpital Roger Salengro
CHU de Limoges - Hôpital Dupuytren
HCL - Hôpital Neurologique P. Wertheimer
APHM - Hôpital de la Timone
CHRU de Montpellier - Hôpital Gui de Chauliac
CHU de Nice - Hôpital Pasteur
APHP - Groupe Hospitalier Pitié-Salpetrière
CENTRE HOSPITALIER DE SAINT BRIEUC - Hôpital Yves Le Foll
CHU de Strasbourg - Hôpital de Hautepierre
CHRU de Tours - Hôpital Bretonneau
Trafford Centre for Biomedical Research
Institute of Neurological Sciences, Queen Elizabeth University Hospital
North-East London and Essex MND Regional Care Centre
King's MND Care and Research Centre
Centre for Neuromuscular Diseases - National Hospital of Neurology
Salford Royal NHS Foundation Trust, Neurology Dept
Sheffield Care and Research Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

low dose interleukin-2

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

Time to death from date of randomization to date of death

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT03039673

First Posted

January 31, 2017

Last Updated

April 1, 2022

Sponsor

Centre Hospitalier Universitaire de Nīmes

1. Study Identification

Unique Protocol Identification Number

NCT03039673

Brief Title

MIROCALS: Modifying Immune Response and OutComes in ALS

Acronym

MIROCALS

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Completed

Study Start Date

June 19, 2017 (Actual)

Primary Completion Date

July 22, 2021 (Actual)

Study Completion Date

July 22, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Centre Hospitalier Universitaire de Nīmes

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyotrophic Lateral Sclerosis

Keywords

interleukin-2, low-dose interleukin-2

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

304 (Actual)

8. Arms, Groups, and Interventions

Arm Title

low dose interleukin-2

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Riluzole

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

IL-2

Other Intervention Name(s)

low dose interleukin-2, ultra low dose interleukin-2

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

5% glucose water solution

Intervention Description

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.

Primary Outcome Measure Information:

Title

Time to death from date of randomization to date of death

Description

Time Frame

Month 21

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nigel Leigh, MD, PhD

Organizational Affiliation

Brighton and Sussex Medical School

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Gilbert Bensimon, MD, PhD

Organizational Affiliation

Centre Hospitalier Universitaire de Nîmes

Official's Role

Study Director

Facility Information:

Facility Name

CHRU de Lille - Hôpital Roger Salengro

City

Lille

ZIP/Postal Code

59037

Country

France

Facility Name

CHU de Limoges - Hôpital Dupuytren

City

Limoges

ZIP/Postal Code

87042

Country

France

Facility Name

HCL - Hôpital Neurologique P. Wertheimer

City

Lyon

ZIP/Postal Code

69677

Country

France

Facility Name

APHM - Hôpital de la Timone

City

Marseille

ZIP/Postal Code

13385

Country

France

Facility Name

CHRU de Montpellier - Hôpital Gui de Chauliac

City

Montpellier Cedex 5

ZIP/Postal Code

34295

Country

France

Facility Name

CHU de Nice - Hôpital Pasteur

City

Nice

ZIP/Postal Code

06002

Country

France

Facility Name

APHP - Groupe Hospitalier Pitié-Salpetrière

City

Paris Cedex 13

ZIP/Postal Code

75651

Country

France

Facility Name

CENTRE HOSPITALIER DE SAINT BRIEUC - Hôpital Yves Le Foll

City

Saint Brieuc

ZIP/Postal Code

22027

Country

France

Facility Name

CHU de Strasbourg - Hôpital de Hautepierre

City

Strasbourg

ZIP/Postal Code

67098

Country

France

Facility Name

CHRU de Tours - Hôpital Bretonneau

City

Tours

ZIP/Postal Code

37044

Country

France

Facility Name

Trafford Centre for Biomedical Research

City

Brighton

ZIP/Postal Code

BN1 9RY

Country

United Kingdom

Facility Name

Institute of Neurological Sciences, Queen Elizabeth University Hospital

City

Glasgow

ZIP/Postal Code

G514TF

Country

United Kingdom

Facility Name

North-East London and Essex MND Regional Care Centre

City

London

ZIP/Postal Code

E1 4NS

Country

United Kingdom

Facility Name

King's MND Care and Research Centre

City

London

ZIP/Postal Code

SE5 8AF

Country

United Kingdom

Facility Name

Centre for Neuromuscular Diseases - National Hospital of Neurology

City

London

ZIP/Postal Code

WC1N 3BG

Country

United Kingdom

Facility Name

Salford Royal NHS Foundation Trust, Neurology Dept

City

Manchester

ZIP/Postal Code

M6 8HD

Country

United Kingdom

Facility Name

Sheffield Care and Research Centre

City

Sheffield

ZIP/Postal Code

S10 2JF

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

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MIROCALS: Modifying Immune Response and OutComes in ALS

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