Amyotrophic Lateral SclerosisPhase 2/3NCT00706147
Phase II/III Randomized, Placebo-controlled Trial of Arimoclomol in SOD1 Positive Familial Amyotrophic Lateral Sclerosis
A Phase 2/3 study testing Arimoclomol in people with Amyotrophic Lateral Sclerosis, run by University of Miami at 2 sites in United States.
Trial summary
The purpose of this study will be to demonstrate the safety, tolerability, and efficacy of arimoclomol in subjects with SOD1 positive familial Amyotrophic Lateral Sclerosis (ALS). This type of ALS is HEREDITARY (runs in families), and at least one other person in the family must have had 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
- 38 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2009to Nov 2016
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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
- Type of ALS that is hereditary (runs in families) only.
- El Escorial criteria for familial ALS and a family history of a pathogenic mutation in a gene known to be associated with ALS, such as the SOD1 gene.
- Willingness to undergo genetic testing and to learn the results.
- Demonstrable mutation in the SOD1 gene that is reported to be associated with a rapid rate of disease progression (i.e. A4V, A4T, C6F, C6G, V7E, L8Q, G10V, G41S, H43R, H48Q, D90V, G93A, D101H, D101Y, L106V, I112M, I112T, R115G, L126X, G127X, A145T, V148G, V148I) or possibly associated with rapidly progressive disease (E21G, G37R, L38V, D76Y, L84F, L84V, N86S, D90A het, G93R, I104F, I113T, L144F, L144S).
- Age 18 years or older; male or female.
- Capable of providing informed consent and complying with trial procedures.
Show all 12Show fewer
- Diagnosis within less than 9 months of the anticipated date of the baseline visit AND study participants' subjective evaluation that they expect their physical condition to permit travel to the study site for both the baseline and 2-month study visits.
- Women must not be able to become pregnant (e.g. post menopausal for at least one year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. Adequate contraception includes: oral contraception, implanted contraception, intrauterine device in place for at least 3 months, or barrier method in conjunction with spermicide.
- Women of childbearing potential must have a negative pregnancy test at screening visit and be non-lactating.
- Willing to remain on a stable dose of Riluzole or to remain off Riluzole for the duration of the trial.
- Identifiable local medical doctor to assist with urgent care of any medical complications that may arise.
- Absence of any of the exclusion criteria.
Who cannot join
- History of known sensitivity or intolerability to Arimoclomol or to any other related compound.
- Exposure to any investigational drug within 30 days of the screening visit.
- Presence of any of the following clinical conditions:
- Substance abuse within the past year.
- Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active infectious disease.
- AIDS or AIDS-related complex.
Show all 16Show fewer
- Unstable psychiatric illness defined as psychosis (hallucinations or delusions), untreated major depression within 90 days of the screening visit.
- Positive pregnancy test at screening visit.
- Screening laboratory values:
- Creatinine greater than 1.5.
- Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST). greater than 3.0 times the upper limit of normal.
- Total bilirubin greater than 2.0 times the upper limit of normal.
- White blood cell (WBC) count less than 3,500/mm3.
- Platelet concentration less than 100,000/ul.
- Hematocrit level less than 33 for female or less than 35 for male.
- Female patients who are breast-feeding.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Miami Miller School of Medicine
Miami, Florida, 33136
About this study
Official title: Phase II/III Randomized, Placebo-Controlled Trial of Arimoclomol in SOD1 Positive Familial Amyotrophic Lateral Sclerosis (ALS)
The purpose of this study will be to demonstrate the safety, tolerability, and efficacy of arimoclomol in subjects with SOD1 positive familial Amyotrophic Lateral Sclerosis (ALS). This type of ALS is HEREDITARY (runs in families), and at least one other person in the family must have had ALS.
Study hypotheses: Arimoclomol, taken at a dose of 200 mg three times daily will improve survival as defined by time to death, tracheostomy or permanent assisted ventilation. In addition, it will be safe and well tolerated in subjects with SOD1 positive familial ALS.
Funding Source - FDA-OOPD
Read the detailed description
Using a seamless, adaptive, phase II/III design, the investigators will determine the safety and efficacy of arimoclomol in patients with SOD1 positive familial ALS. Both stage-1 and stage-2 are randomized, double-blind and placebo-controlled in a population of patients with rapidly progressive SOD1 positive familial ALS. Patients with ALS, a history of a relative affected with ALS (i.e. familial ALS) and the presence of a demonstrable mutation in the SOD1 gene that is known to be associated with rapidly progressive disease, will be eligible for inclusion in this study. Potentially eligible subjects will undergo screening via telephone and, if necessary, review of outside medical records. The intervention will continue for up to 12 months. In the event that a participant reaches a study endpoint (e.g. tracheostomy or permanently assisted ventilation) study drug will be terminated. Subjects who meet all eligibility criteria will travel a study site for final eligibility determination, baseline evaluation and will then be randomized 1:1 to receive either placebo or arimoclomol at a dose of 200 mg t.i.d. Participants will then be evaluated again in person at a study site at Month-2. Telephonic evaluations at Month-1, 3, 4, 5, 6, 8, and 10 will be performed in participants' homes. Safety and tolerability evaluations will be performed at each of these visits. Collection of blood samples for safety laboratory analyses and measurement of blood pressure, heart rate, respiratory rate, temperature and weight will be performed at Months-1, 3, 4, 5, 6, 8, and 10 in the participant's home by a representative of a medical monitoring company. A study coordinator may perform an in-person visit at Month-12, or this visit may occur telephonically. A final evaluation will be performed via telephone at Month-13 (30 days after the last dose of study medication).
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Arimoclomol, Placebo
- Keywords
- Hereditary ALS, Hereditary neurological disease, Lou Gehrig's Disease, Motor Neuron Disease, Amyotrophic Lateral Sclerosis (ALS), Familial ALS, Neuromuscular disease, SOD1 mutation, Superoxide dismutase, SOD1 positive ALS, inherited ALS
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Motor Neuron Disease, Neuromuscular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ArimoclomolDrug
Also called Arimoclomol (BRX-345)
Drug: Arimoclomol capsules given three times per day
PlaceboDrug
Drug: Placebo capsules given three times per day
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | Not described Receives: Drug: Placebo |
| 2 | Active comparator | Not described Receives: Drug: Arimoclomol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to death, tracheostomy or permanent assisted ventilation will be the primary outcome measure.
Measured: 12 months
Secondary outcomes (3)
Rate of decline of ALSFRS-R (ALS functional rating scale-revised) over a period of up to 12 months.
Measured: 12 months
Disease progression as measured by the rate of decline of FEV6.
Measured: 12 months
Safety and tolerability of arimoclomol will be evaluated by using vital signs and weight, clinical laboratory measures, physical examination, report of adverse events, and the proportion of subjects completing the study on assigned treatment.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2008 (estimated)
- Study startJan 2009
- Primary completionDec 2014
- Study completionNov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by University of MiamiThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Collaborators
- Massachusetts General Hospital
- Responsible party
- Principal investigator, Michael Benatar, University of Miami
- Investigators
- Michael Benatar, MBChB, DPhil, Principal investigator, University of MiamiMerit Cudkowicz, MD, MSc, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00706147
- Sponsor's protocol ID
- 20100758
- Other IDs
- 3517
- Status last verified
- Jan 2019
- First submitted
- 24 Jun 2008
- Last updated
- 11 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Benatar M, Wuu J, Andersen PM, Atassi N, David W, Cudkowicz M, Schoenfeld D. Randomized, double-blind, placebo-controlled trial of arimoclomol in rapidly progressive SOD1 ALS. Neurology. 2018 Feb 13;90(7):e565-e574. doi: 10.1212/WNL.0000000000004960. Epub 2018 Jan 24.
PubMed 29367439
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II/III Randomized, Placebo-Controlled Trial of Arimoclomol in SOD1 Positive Familial Amyotrophic Lateral Sclerosis (ALS)
- ClinicalTrials.gov ID
- NCT00706147
- Acronym / sponsor ID
- 20100758
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- Hereditary ALS, Hereditary neurological disease, Lou Gehrig's Disease, Motor Neuron Disease, Amyotrophic Lateral Sclerosis (ALS), Familial ALS, Neuromuscular disease, SOD1 mutation
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Collaborators
- Massachusetts General Hospital
- Study start
- Jan 2009
- Primary completion
- Dec 2014 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 27 Jun 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study will be to demonstrate the safety, tolerability, and efficacy of arimoclomol in subjects with SOD1 positive familial Amyotrophic Lateral Sclerosis (ALS). This type of ALS is HEREDITARY (runs in families), and at least one other person in the family must have had ALS.
Study hypotheses: Arimoclomol, taken at a dose of 200 mg three times daily will improve survival as defined by time to death, tracheostomy or permanent assisted ventilation. In addition, it will be safe and well tolerated in subjects with SOD1 positive familial ALS.
Funding Source - FDA-OOPD
Detailed description
Using a seamless, adaptive, phase II/III design, the investigators will determine the safety and efficacy of arimoclomol in patients with SOD1 positive familial ALS. Both stage-1 and stage-2 are randomized, double-blind and placebo-controlled in a population of patients with rapidly progressive SOD1 positive familial ALS. Patients with ALS, a history of a relative affected with ALS (i.e. familial ALS) and the presence of a demonstrable mutation in the SOD1 gene that is known to be associated with rapidly progressive disease, will be eligible for inclusion in this study. Potentially eligible subjects will undergo screening via telephone and, if necessary, review of outside medical records. The intervention will continue for up to 12 months. In the event that a participant reaches a study endpoint (e.g. tracheostomy or permanently assisted ventilation) study drug will be terminated. Subjects who meet all eligibility criteria will travel a study site for final eligibility determination, baseline evaluation and will then be randomized 1:1 to receive either placebo or arimoclomol at a dose of 200 mg t.i.d. Participants will then be evaluated again in person at a study site at Month-2. Telephonic evaluations at Month-1, 3, 4, 5, 6, 8, and 10 will be performed in participants' homes. Safety and tolerability evaluations will be performed at each of these visits. Collection of blood samples for safety laboratory analyses and measurement of blood pressure, heart rate, respiratory rate, temperature and weight will be performed at Months-1, 3, 4, 5, 6, 8, and 10 in the participant's home by a representative of a medical monitoring company. A study coordinator may perform an in-person visit at Month-12, or this visit may occur telephonically. A final evaluation will be performed via telephone at Month-13 (30 days after the last dose of study medication).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Placebo comparator | Drug: Placebo |
| 2 | Active comparator | Drug: Arimoclomol |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Type of ALS that is hereditary (runs in families) only.
- El Escorial criteria for familial ALS and a family history of a pathogenic mutation in a gene known to be associated with ALS, such as the SOD1 gene.
- Willingness to undergo genetic testing and to learn the results.
- Demonstrable mutation in the SOD1 gene that is reported to be associated with a rapid rate of disease progression (i.e. A4V, A4T, C6F, C6G, V7E, L8Q, G10V, G41S, H43R, H48Q, D90V, G93A, D101H, D101Y, L106V, I112M, I112T, R115G, L126X, G127X, A145T, V148G, V148I) or possibly associated with rapidly progressive disease (E21G, G37R, L38V, D76Y, L84F, L84V, N86S, D90A het, G93R, I104F, I113T, L144F, L144S).
- Age 18 years or older; male or female.
Key exclusion criteria (16 listed)
- History of known sensitivity or intolerability to Arimoclomol or to any other related compound.
- Exposure to any investigational drug within 30 days of the screening visit.
- Presence of any of the following clinical conditions:
- Screening laboratory values:
- Female patients who are breast-feeding.
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 |
|---|---|---|
| ArimoclomolAlso: Arimoclomol (BRX-345)Drug: Arimoclomol capsules given three times per day | Drug | 2 |
| PlaceboDrug: Placebo capsules given three times per day | Drug | 1 |
Primary outcome
Time to death, tracheostomy or permanent assisted ventilation will be the primary outcome measure.
Time frame: 12 months
3 secondary outcomes
Rate of decline of ALSFRS-R (ALS functional rating scale-revised) over a period of up to 12 months.
Time frame: 12 months
Disease progression as measured by the rate of decline of FEV6.
Time frame: 12 months
Safety and tolerability of arimoclomol will be evaluated by using vital signs and weight, clinical laboratory measures, physical examination, report of adverse events, and the proportion of subjects completing the study on assigned treatment.
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2019.
- Derived from this study: PubMed 29367439Benatar M, Wuu J, Andersen PM, Atassi N, David W, Cudkowicz M, Schoenfeld D. Randomized, double-blind, placebo-controlled trial of arimoclomol in rapidly progressive SOD1 ALS. Neurology. 2018 Feb 13;90(7):e565-e574. doi: 10.1212/WNL.0000000000004960. Epub 2018 Jan 24.
Related trials for Amyotrophic Lateral Sclerosis
RecruitingPhase 1/2
Study is to Assess the Safety and Tolerability of VTx-002 in Participants With ALS
Amyotrophic Lateral Sclerosis
Not yet recruiting
A Study on the Addition of Alsum30 for the Treatment of Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis (ALS), Bacillus Coagulans
Active, not recruiting
Functional Outcomes and Control Using Synchron BCI - Australia
Neurologic Disorder, Neurologic Diseases
Not yet recruitingPhase 1
Safety, Tolerability, and Pharmacodynamic Exploration of Orelabrutinib in Patients With Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic Lateral Sclerosis (ALS)
Recruiting
Clinical Outcome Assessment for AT & BCI
Spinal Cord Injury, ALS (Amyotrophic Lateral Sclerosis)
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, MBChB, DPhil principal investigator
University of Miami
Merit Cudkowicz, MD, MSc principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Arimoclomol in people with Amyotrophic Lateral Sclerosis, run by University of Miami at 2 sites in United States.
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 12 inclusion and 16 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 11 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Time to death, tracheostomy or permanent assisted ventilation will be the primary outcome measure. (time frame: 12 months). 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 NCT00706147, 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 11 Jan 2019.