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Amyotrophic Lateral SclerosisPhase 3MITOTARGETNCT00868166

Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS

A Phase 3 study testing Olesoxime and Riluzole in people with Amyotrophic Lateral Sclerosis, run by Hoffmann-La Roche at 15 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of the assay is to assess the safety and the efficacy of TRO19622 330 mg QD as add-on therapy to riluzole 50 mg bid in the treatment of patients suffering from ALS, as compared to placebo, assessed by the 18-month survival rate. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Amyotrophic Lateral Sclerosis
What is being tested?
Olesoxime and Riluzole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
512 participants
Where
15 sitesin 5 countries
Study dates
30 Apr 2009to 30 Sep 2011
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with sporadic or familial Amyotrophic Lateral Sclerosis
  • Patients with a clinical diagnosis of laboratory-supported probable, probable, or definite ALS according to the modified El Escorial criteria8.
  • Have signed an Informed Consent to participate to the trial before any study related procedure has taken place.
  • Be of age >18 (exclusive) and < 80 years (inclusive).
  • If a female, not lactating, has a negative pregnancy test and agrees to use an effective method of birth control.
  • Onset of ALS Symptoms (weakness) for more than 6 months (inclusive) and less than 36 months(inclusive).
  • Slow vital capacity (SVC), measured three times, one of the measure being >/= 70% of that predicted.
  • Treated with riluzole at the stable dose of 50 mg bid for at least 30 days before enrolment.

Who cannot join

  • Tracheostomy, invasive ventilation, or non invasive positive pressure ventilation (NIPPV).
  • Gastrostomy.
  • Evidence of major psychiatric disorder or clinically evident dementia.
  • Diagnosis of a neurodegenerative disease in addition to ALS.
  • Have a current medication that could interfere with TRO19622 pharmacokinetics: tamoxifene.
  • Have current medications that could interfere with TRO19622 absorption such as ezetimibe, bile salts chelators (cholesteramine), fibrates, phytosterols, niacin (vitamin B3),fish oils. Have a current medication of lipid lowering agents other than statins.
Show all 20Show fewer
  • Known hypersensitivity to any component of the study drug.
  • Patients with known intolerance or contra-indication to riluzole.
  • Have a recent history (within the previous 6 months) or current evidence of alcohol or drug abuse.
  • Have concurrent unstable disease involving any system eg, carcinoma other than basal cell carcinoma, any cardiac dysrhythmia, myocardial infarction, clinical or ECG signs of myocardial ischemia, cardiac insufficiency, angina symptoms, current symptoms of Coronary Artery Disease, or any other condition that in the opinion of the Investigator would make the patient unsuitable for study participation.
  • . In Germany: Have any cardiac dysrhythmia, myocardial infarction, clinical or ECG signs of myocardial ischemia, cardiac insufficiency, angina symptoms, current symptoms of Coronary Artery Disease or any cardiovascular illness known or identified at the screening or inclusion visits, or have concurrent unstable disease involving any system eg, carcinoma other than basal cell carcinoma or any other condition that in the opinion of the Investigator would make the patient unsuitable for study participation.
  • Having a baseline QTc (Bazett) > 450 msec for males and > 470 msec for females.
  • Patients with known hepatitis B/C or HIV positive serology.
  • Be pregnant female or lactating.
  • Have renal impairment defined as blood creatinine > 1:5 X upper limit of normal.
  • Have hepatic impairment and/or liver enzymes (ALAT or ASAT) > 3 X ULN.
  • Hemostasis disorders or current treatment with oral anticoagulants.
  • Be possibly dependent on the Investigator or the Sponsor (eg, including, but not limited to, affiliated employee).
  • Participated in any other investigational drug or therapy study with a non approved medication, within the previous 3 months.
  • Patients without Social Security Insurance (France).

Trial locations and contacts

15 sites in 5 countries.

15 sites in 5 countries

France7 sites

  • HCL Hôpital Neurologique et Neurochirurgical Pierre Wertheimer - Neurologie C et Laboratoire d'électromyographie - 59, boulevard Pinel

    Bron, 69677

  • CHRU de LILLE - Hôpital Roger Salengro - Centre SLA-MMN - Sce de Neurologie et Pathologie du Mouvement

    Lille, 59037

  • Centre SLA Limoges - Service de Neurologie

    Limoges, 87042

  • Hôpital La Timone - Service Neurologie et Maladies Neuromusculaires

    Marseille, 13005

  • Clinique du Motoneurone - Sce d'Explorations Neurologiques - Hôpital Gui de Chauliac

    Montpellier, 34295

  • CHU de Nice - Hôpital de l'Archet 1 - Centre de Référence pour les Maladies Neuromusculaires et la SLA

    Nice, 06202

  • Groupe Hospitalier PITIE-SALPETRIERE - Fédération des Maladies du Système Nerveux

    Paris, 75013

Other trials in France

Germany4 sites

  • Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Neurologische Poliklinik Ambulanz für ALS und andere Motoeneuronenerkrankungen

    Berlin, 13353

  • Universitätsklinik und Poliklinik für Neurologie - Martin-Luther-Universität Halle-Wittenberg

    Halle, 06097

  • Neurologische Klinik Medizinische Hochschule

    Hanover, D-30623

  • Universitäts- und Rehabilitationskliniken Ulm (RKU) - Neurologische Universitätsklinik

    Ulm, 89081

Other trials in Germany

United Kingdom2 sites

  • King's MND Care and Research Center - Academic Neurosciences Building PO Box 41 Institute of Psychiatry

    London, SE58AF

  • Academic Neurology Unit - University of Sheffield - Section of Neuroscience - Division of Genomic Medicine - School of Medicine and Biomedical Sciences

    Sheffield, S10 2RX

Other trials in United Kingdom

Belgium1 site

  • University Hospital Gasthuisberg - Dept Neurology - Herestraat 49

    Leuven, 3000

Other trials in Belgium

Spain1 site

  • Hospital Carlos III - Unidad de ELA - Sinesio Delgado, 10

    Madrid, 28029

Other trials in Spain

About this study

Official title: Phase II/III, Multicenter, Randomized, Parallel Group, Double-blind, Placebo Controlled Study to Assess Safety and Efficacy of TRO19622 in Amyotrophic Lateral Sclerosis (ALS) Patients Treated With Riluzole

The purpose of the assay is to assess the safety and the efficacy of TRO19622 330 mg QD as add-on therapy to riluzole 50 mg bid in the treatment of patients suffering from ALS, as compared to placebo, assessed by the 18-month survival rate.

Read the detailed description

A stand alone treatment with TRO19622 is not acceptable for ethical reasons. Riluzole is an approved and widely used ALS treatment in the European community, in Japan and in the USA.

Therefore, in this study, TRO19622 will be assessed as add-on to riluzole in patients suffering from ALS.

At the start of the study, patients will be randomized to one of two groups : TRO19622 (330 mg QD or placebo (once a day).

Each treatment will be administered for 18 months under double-blind conditions. The product under evaluation will be administered to patients receiving the standard of care for ALS, including riluzole.

Riluzole dosage (50 mg bid) must be stable and well tolerated for at least one month prior to inclusion into the study.

After the double-blind period, open-label administration of TRO19622 will be allowed for safety and survival assessments and until efficacy results are available.

A separate open-label protocol will be written 6 months after the randomization of the last patient into the study.

Being tested
Olesoxime, Placebo Comparator, Riluzole
Keywords
Amyotrophic Lateral Sclerosis, TRO19622, Trophos
Medical subject headings
Amyotrophic Lateral Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OlesoximeDrug

    Also called TRO19622

    2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzol 50mg bid

  • Placebo ComparatorDrug

    Also called Placebo

    2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid

  • RiluzoleDrug

    Also called Rilutek

    Riluzole given as add-on therapy 50mg bid

Study groups in NCT00868166
Study groupRoleWhat they receive
OlesoximeExperimental2 Capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid
Receives: Drug: Olesoxime; Drug: Riluzole
Placebo ComparatorPlacebo comparator2 Capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid
Receives: Drug: Placebo Comparator; Drug: Riluzole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival Rate at 18 Months

    Overall survival was defined from the date of randomization until the date of death (event) or last known alive date (censored). If the death date was after 18 months, the participant was censored at 18 months (548 days). Participants still alive at or after 18 months were censored at 18 months/ 548 days. All data over the 18-month follow-up period after randomization, and participant survival status at the 18-month follow-up visit for participants who withdrew prematurely from the study for reasons other than death were included.

    Measured: From the date of randomization until the date of death or last follow-up censored at 18 months (548 days)

Secondary outcomes (7)

  1. Percentage of Participants With Failure Over 18 Months

    Time to failure was defined as the time from randomization to the time of the first event to consider (Tracheostomy, invasive ventilation [IV] or non invasive ventilation [NIV])

    Measured: From randomization to the time of the first event to consider at 18 months (548 days)

  2. Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R)

    The ALSFRS-R is an ordinal rating scale (0 through 4) used to determine the ALS participant's self assessment of their ability and need for assistance in 12 activities or functions. This is a validated scale, both in person and by phone, which provides a total score from four sub-scores which assess speech and swallowing, (bulbar function), use of upper extremities (cervical function), gait and turning in bed (lumbar function), and breathing (respiratory function). Total scores range from 0 (most impaired) to 48 (normal ability).

    Measured: Inclusion, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18

  3. Percentage of Participants With a Global ALS FRS-R Score of <30 or Death

    Percentage of participants with a global ALS FRS-R score of < 30 or death was estimated using the Kaplan-Meier method in the ITT, with a two-tailed log-rank, both stratified by site of onset (bulbar or spinal) and non-stratified. The ALSFRS-R is an ordinal rating scale (0 through 4) used to determine the ALS participant's self assessment of their ability and need for assistance in 12 activities or functions. This is a validated scale, both in person and by phone, which provides a total score from four sub-scores which assess speech and swallowing, (bulbar function), use of upper extremities (cervical function), gait and turning in bed (lumbar function), and breathing (respiratory function). Total scores range from 0 (most impaired) to 48 (normal ability).

    Measured: Month 18 (548 days)

  4. Slow Vital Capacity (SVC) Percent Predicted

    SVC as a percent of the predicted value was evaluated and reported.

    Measured: Baseline, Inclusion, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18

  5. Percentage of Participants With SVC Percent Predicted <70% or Had Died Over 18 Months

    Measured: Month 18 (548 days)

  6. Global Score of Manual Muscle Testing (MMT) of 34 Muscle Groups

    MMT score involved the examination of 30 items. These 30 items are scored from 0 (no trace of contraction) to 5 (normal power at first try). The global score is the sum of the item scores and can range from 0 to 150. Higher score indicates some power.

    Measured: Inclusion, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18

  7. The Single-Item Mc Gill Quality of Life Scale

    The single-item McGill quality of life scale evaluated the following question "Considering all parts of my life - physical, emotional, social, spiritual, and financial - over the past two (2) days, the quality of my life has been…"as a score of 1 to 10 on a visual analog scale where 0 is very bad and 10 is excellent.

    Measured: Inclusion, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Mar 2009 (estimated)
  2. Study start30 Apr 2009
  3. Primary completion30 Sep 2011
  4. Study completion30 Sep 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
512 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00868166
Sponsor's protocol ID
WN29853
Other IDs
EudraCT Number:2008-007320-25, TRO19622 CL E Q 1015-1
Acronym
MITOTARGET
Status last verified
Feb 2020
First submitted
23 Mar 2009
Last updated
25 Feb 2020
Data monitoring committee
Yes

Publications

  • Witzel S, Frauhammer F, Steinacker P, Devos D, Pradat PF, Meininger V, Halbgebauer S, Oeckl P, Schuster J, Anders S, Dorst J, Otto M, Ludolph AC. Neurofilament light and heterogeneity of disease progression in amyotrophic lateral sclerosis: development and validation of a prediction model to improve interventional trials. Transl Neurodegener. 2021 Aug 26;10(1):31. doi: 10.1186/s40035-021-00257-y.

    PubMed 34433481

  • Devos D, Moreau C, Kyheng M, Garcon G, Rolland AS, Blasco H, Gele P, Timothee Lenglet T, Veyrat-Durebex C, Corcia P, Dutheil M, Bede P, Jeromin A, Oeckl P, Otto M, Meininger V, Danel-Brunaud V, Devedjian JC, Duce JA, Pradat PF. A ferroptosis-based panel of prognostic biomarkers for Amyotrophic Lateral Sclerosis. Sci Rep. 2019 Feb 27;9(1):2918. doi: 10.1038/s41598-019-39739-5.

    PubMed 30814647

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Olesoxime and Riluzole in people with Amyotrophic Lateral Sclerosis, run by Hoffmann-La Roche at 15 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in France, Germany, United Kingdom, Belgium, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival Rate at 18 Months (time frame: From the date of randomization until the date of death or last follow-up censored at 18 months (548 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00868166, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2020.

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