Amyotrophic Lateral SclerosisPhase 3NCT03491462
Arimoclomol in Amyotropic Lateral Sclerosis
A Phase 3 study testing Arimoclomol in people with Amyotrophic Lateral Sclerosis, run by ZevraDenmark at 29 sites in 12 countries.
Trial summary
A multicenter, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of arimoclomol in amyotropic lateral sclerosis (ALS) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Arimoclomol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 245 participants
- Where
- 29 sitesin 12 countries
- Study dates
- 31 Jul 2018to 18 Dec 2020
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject meets revised El Escorial criteria for clinically possible, clinically probable / clinically probable ALS laboratory-supported, clinically definite ALS or clinically definite familial ALS laboratory-supported
- 18 months or less since first appearance of weakness (e.g. limb weakness, dysarthria, dysphagia, shortness of breath)
- ALS Functional Rating Scale-Revised (ALSFRS-R) equal to or above 35 and erect (seated) Slow Vital Capacity (SVC) % predicted equal to or above 70% at Screening
Who cannot join
- Tracheostomy or use of non-invasive ventilation for more than 2 hours during waking hours at the time of Screening and Baseline
- Pregnant or breast-feeding
- Current or anticipated use of diaphragmatic pacing
- Any other relevant medically significant condition which could present risk to the subject or interfere with the assessment of safety or has an increased risk of causing death during the trial
Trial locations and contacts
29 sites in 12 countries.
29 sites in 12 countries
United States10 sites
University of Virginia Health System
Charlottesville, Virginia, 22908
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
University of Kansas Medical Center (KUMC) - Landon Center on Aging
Kansas City, Kansas, 66160
University of Miami
Miami, Florida, 33136
Hospital for Special Surgery
New York, New York, 10021
UC Irvine Health ALS and Neuromuscular Center
Orange, California, 92868
University of Pensylvania, Perelman Center for Advanced Medicine - Penn Neuroscience Center
Philadelphia, Pennsylvania, 19107
St. Joseph's Hospital and Medical Center (SJHMC) - Barrow Neurological Institute (BNI) - The Gregory W. Fulton ALS and Neuromuscular Disease Center
Phoenix, Arizona, 85013
HonorHealth Neurology
Phoenix, Arizona, 85018
Providence Brain & Spine Institute
Portland, Oregon, 97213
Canada3 sites
London Health Sciences Centre
London, Ontario, N6A 5A5
Montreal Neurological Institute and Hospital
Montreal, Quebec, H3A 2B4
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Germany3 sites
Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK) - Ambulanz fuer ALS und andere Motoneuronenerkrankungen
Berlin, 13353
Medizinische Hochschule Hannover (MHH) - Klinik fuer Neurologie
Hanover, 30625
Universitaetsklinikum Ulm - Klinik fuer Neurologie
Ulm, 89081
France2 sites
Centre Hospitalier Regional Universitaire (CHRU) Montpellier - Hopital Gui De Chauliac
Montpellier, 34295
Groupe Hospitalier Pitie-Salpetriere - Centre d'Investigation Clinique Neurosciences 1422
Paris, 75013
Italy2 sites
Instituti Clinica Scientifici Maugeri - IRCCS
Milan, 20138
Azienda Ospedaliero Universitaria (AUO) di Torino - Citta'della Salute e della Scienza di Torino
Torino, 10126
Poland2 sites
Centrum Medyczne NeuroProtect
Warsaw, 01-684
Citi Clinic
Warsaw, 02-473
Spain2 sites
Hospital Universitario Vall d'Hebron ALS Unit. Consultas Externas; Office: 9-10-11
Barcelona, 08035
Hospital Carlos III - Hospital Universitario La Paz, ALS Unit
Madrid, 28046
Switzerland1 site
Kantonsspital St.Gallen, Muskelzentrum/ALS Clinic
Sankt Gallen, 9007
United Kingdom1 site
Leonard Wolfson Experimental Neurology Centre
London, WC1N 3BG
About this study
Official title: A Phase 3, Randomised, Placebo-Controlled Trial of Arimoclomol in Amyotropic Lateral Sclerosis
A multicenter, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of arimoclomol in amyotropic lateral sclerosis (ALS)
Read the detailed description
Screening up to 4 weeks Treatment up to 76 weeks
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Arimoclomol, Placebo
- Keywords
- Arimoclomol, ALS
- 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.
ArimoclomolDrug
2 capsules (2 x 124 mg arimoclomol base; equivalent to 2 x 200 mg arimoclomol citrate) taken 3 times daily
PlaceboDrug
2 matched placebo capsules taken 3 times daily
| Study group | Role | What they receive |
|---|---|---|
| Arimoclomol | Experimental | 248 mg arimoclomol base (equivalent to 400 mg arimoclomol citrate) 3 times daily Receives: Drug: Arimoclomol |
| Placebo | Placebo comparator | 248 mg matching placebo 3 times daily Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Combined Assessment of Function and Survival (CAFS)
Combined Assessment of Function and Survival (CAFS) is a composite endpoint that includes 1) the change from baseline in revised ALS functional rating scale (ALSFRS-R) and 2) the survival endpoint (time to permanent assisted ventilation [PAV], tracheostomy or death).
On the ALSFRS-R, 12 functions are rated on 5-point ordinal rating scales (from 0 to 4) with a total score range (minimum and maximum score) of 0-48 (sum of all 12 items). The higher the score the better functioning.
For the survival endpoint, the longer time to PAV, tracheostomy, or death the better outcome.
A patient's CAFS score represents a patient's rank in the study based on comparing the patient's outcome for both the change in ALSFRS-R and the time to event (PAV, tracheostomy, or death) to the outcome for all other patients in the study in a pairwise fashion. A higher rank score (range 0-1) is considered a better outcome.
The reported values are the mean rank scores in each group for the composite endpoint.
Measured: Over 76 Weeks
Secondary outcomes (3)
Time to Permanent Assisted Ventilation (PAV) / Tracheostomy / Death
Time from baseline to one of the events (PAV / tracheostomy / death). PAV is defined as the first of 7 consecutive days on which PAV was used for >22 hours/day
Measured: Over 76 weeks
Change From Baseline to Week 76 (or End-of-trial) in the Revised ALS Functional Rating Scale (ALSFRS-R)
The ALSFRS-R score is based on a rating scale where 12 functions are rated on 5-point ordinal rating scales (from 0 to 4) with a maximum score of 48 (sum of all 12 items). The higher the score the better functioning.
Measured: Week 76 (or end of trial)
Change From Baseline to Week 76 (or End-of-trial) in Percent (%) Predicted Slow Vital Capacity (SVC)
Slow Vital Capacity (SVC) is a measure of breathing function. SVC measures the volume that can be exhaled from a full inhalation after exhaling to a maximum as slowly as possible. The percent (%) of predicted SVC is reported.
Measured: Week 76 (or end of trial)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2018
- Study start31 Jul 2018
- Primary completion18 Dec 2020
- Study completion18 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Placebo-controlled, parallel group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 245 participants (actual)
Sponsor and investigators
- Lead sponsor
- ZevraDenmark
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael Benatar, MD PhD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03491462
- Sponsor's protocol ID
- ORARIALS-01
- Status last verified
- Aug 2023
- First submitted
- 27 Mar 2018
- Last updated
- 24 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Benatar M, Hansen T, Rom D, Geist MA, Blaettler T, Camu W, Kuzma-Kozakiewicz M, van den Berg LH, Morales RJ, Chio A, Andersen PM, Pradat PF, Lange D, Van Damme P, Mora G, Grudniak M, Elliott M, Petri S, Olney N, Ladha S, Goyal NA, Meyer T, Hanna MG, Quinn C, Genge A, Zinman L, Jabari D, Shoesmith C, Ludolph AC, Neuwirth C, Nations S, Shefner JM, Turner MR, Wuu J, Bennett R, Dang H, Sundgreen C; ORARIALS-01 trial team. Safety and efficacy of arimoclomol in patients with early amyotrophic lateral sclerosis (ORARIALS-01): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Neurol. 2024 Jul;23(7):687-699. doi: 10.1016/S1474-4422(24)00134-0. Epub 2024 May 20.
PubMed 38782015
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomised, Placebo-Controlled Trial of Arimoclomol in Amyotropic Lateral Sclerosis
- ClinicalTrials.gov ID
- NCT03491462
- Acronym / sponsor ID
- ORARIALS-01
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- Arimoclomol, ALS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 245 participants (actual)
- Lead sponsor
- ZevraDenmarkIndustry (pharma, biotech, devices)
- Study start
- 31 Jul 2018 (actual)
- Primary completion
- 18 Dec 2020 (actual)
- Study completion
- 18 Dec 2020 (actual)
- First posted
- 9 Apr 2018 (actual)
- Results
- Posted 24 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A multicenter, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of arimoclomol in amyotropic lateral sclerosis (ALS)
Detailed description
Screening up to 4 weeks Treatment up to 76 weeks
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Placebo-controlled, parallel group
| Arm | Type | Receives |
|---|---|---|
| Arimoclomol | Experimental | Drug: Arimoclomol248 mg arimoclomol base (equivalent to 400 mg arimoclomol citrate) 3 times daily |
| Placebo | Placebo comparator | Drug: Placebo248 mg matching placebo 3 times daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Subject meets revised El Escorial criteria for clinically possible, clinically probable / clinically probable ALS laboratory-supported, clinically definite ALS or clinically definite familial ALS laboratory-supported
- 18 months or less since first appearance of weakness (e.g. limb weakness, dysarthria, dysphagia, shortness of breath)
- ALS Functional Rating Scale-Revised (ALSFRS-R) equal to or above 35 and erect (seated) Slow Vital Capacity (SVC) % predicted equal to or above 70% at Screening
Key exclusion criteria (4 listed)
- Tracheostomy or use of non-invasive ventilation for more than 2 hours during waking hours at the time of Screening and Baseline
- Pregnant or breast-feeding
- Current or anticipated use of diaphragmatic pacing
- Any other relevant medically significant condition which could present risk to the subject or interfere with the assessment of safety or has an increased risk of causing death during the trial
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Arimoclomol2 capsules (2 x 124 mg arimoclomol base; equivalent to 2 x 200 mg arimoclomol citrate) taken 3 times daily | Drug | Arimoclomol |
| Placebo2 matched placebo capsules taken 3 times daily | Drug | Placebo |
Primary outcome
Combined Assessment of Function and Survival (CAFS)
Time frame: Over 76 Weeks
Combined Assessment of Function and Survival (CAFS) is a composite endpoint that includes 1) the change from baseline in revised ALS functional rating scale (ALSFRS-R) and 2) the survival endpoint (time to permanent assisted ventilation [PAV], tracheostomy or death). On the ALSFRS-R, 12 functions are rated on 5-point ordinal rating scales (from 0 to 4) with a total score range (minimum and maximum score) of 0-48 (sum of all 12 items). The higher the score the better functioning. For the survival endpoint, the longer time to PAV, tracheostomy, or death the better outcome. A patient's CAFS score represents a patient's rank in the study based on comparing the patient's outcome for both the change in ALSFRS-R and the time to event (PAV, tracheostomy, or death) to the outcome for all other patients in the study in a pairwise fashion. A higher rank score (range 0-1) is considered a better outcome. The reported values are the mean rank scores in each group for the composite endpoint.
3 secondary outcomes
Time to Permanent Assisted Ventilation (PAV) / Tracheostomy / Death
Time frame: Over 76 weeks
Change From Baseline to Week 76 (or End-of-trial) in the Revised ALS Functional Rating Scale (ALSFRS-R)
Time frame: Week 76 (or end of trial)
Change From Baseline to Week 76 (or End-of-trial) in Percent (%) Predicted Slow Vital Capacity (SVC)
Time frame: Week 76 (or end of trial)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38782015Benatar M, Hansen T, Rom D, Geist MA, Blaettler T, Camu W, Kuzma-Kozakiewicz M, van den Berg LH, Morales RJ, Chio A, Andersen PM, Pradat PF, Lange D, Van Damme P, Mora G, Grudniak M, Elliott M, Petri S, Olney N, Ladha S, Goyal NA, Meyer T, Hanna MG, Quinn C, Genge A, Zinman L, Jabari D, Shoesmith C, Ludolph AC, Neuwirth C, Nations S, Shefner JM, Turner MR, Wuu J, Bennett R, Dang H, Sundgreen C; ORARIALS-01 trial team. Safety and efficacy of arimoclomol in patients with early amyotrophic lateral sclerosis (ORARIALS-01): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Neurol. 2024 Jul;23(7):687-699. doi: 10.1016/S1474-4422(24)00134-0. Epub 2024 May 20.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Benatar, MD PhD principal investigator
University of Miami
29 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Arimoclomol in people with Amyotrophic Lateral Sclerosis, run by ZevraDenmark at 29 sites in 12 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 3 inclusion and 4 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 24 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Canada, Germany, France, Italy and 7 more countries. 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 24 Aug 2023). 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?
Combined Assessment of Function and Survival (CAFS) (time frame: Over 76 Weeks). 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 NCT03491462, which also lists 1 linked publication.
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 24 Aug 2023.