Amyotrophic Lateral SclerosisPhase 2NCT00561366
A Multicenter, Double-Blind Study to Investigate the Safety and Efficacy of Arimoclomol in Volunteers With ALS
A Phase 2 study testing Arimoclomol in people with Amyotrophic Lateral Sclerosis, run by CytRx at 35 sites in 2 countries.
Trial summary
Arimoclomol is a small molecule that upregulates "molecular chaperones" in cells under stress. Arimoclomol extends survival by five weeks when given both pre-symptomatically and at disease onset in a mutant superoxide dismutase (SOD1) transgenic mouse model of 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
- 0 participants
- Where
- 35 sitesin 2 countries
- Study dates
- Start not givento not given
- Phase
- Phase 2
- 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
- Familial or sporadic ALS.
- Diagnosed with laboratory-supported probable, probable or definite ALS according to the World Federation of Neurology El Escorial criteria for less than or equal to 36 months' duration prior to the Screening Visit.
- Vital capacity (VC) equal to or greater than 70% predicted value for gender, height and age at the Screening Visit.
- Geographic accessibility to the study site.
- Ability to take oral medication at the Screening Visit, based on verbal report.
- Fluency in English, Spanish or Canadian French.
Who cannot join
- History of known sensitivity or intolerability to arimoclomol or to any other related compound.
- Prior exposure to arimoclomol through a clinical trial or physician-sponsored IND.
- Exposure to any investigational agent 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 malignancy or infectious disease
Show all 10Show fewer
- AIDS or AIDS-related complex
- Unstable psychiatric illness defined as psychosis (hallucinations or delusions), untreated major depression within 90 days of the Screening Visit.
- Laboratory values: Screening serum creatinine greater than or equal to 1.5 mg/dL, creatinine clearance less than 70 cc/min, alanine aminotransferase (ALT) greater than 3.0 times the upper limit of normal, total bilirubin greater than 1.5 times the upper limit of normal, white blood cell (WBC) count less than 3,500/mm3, platelet concentration of <100,000/ul, hematocrit level of less than 33 % for female or less than 35 % for male, or coagulation tests (PT, PTT) greater than or equal to 1.5 times upper limit of normal.
- Female volunteers who are breast-feeding.
Trial locations and contacts
35 sites in 2 countries.
35 sites in 2 countries
United States31 sites
Upstate Clinical Research, LLC - Tier 2 Site
Albany, New York, 12205
Emory University - Tier 2 site
Atlanta, Georgia, 30322
John Hopkins University - Tier 2 Site
Baltimore, Maryland, 21287
Massachusetts General Hospital - Tier 1 Site
Boston, Massachusetts, 02114
University of Vermont, College of Medicine - Tier 2
Burlington, Vermont, 05405
University of Virginia - Tier 2 Sites
Charlottesville, Virginia, 22908
Northwestern University, Dept. of Neurology - Tier 2 Site
Chicago, Illinois, 60611
Cleveland Clinic Foundation -Tier 2 site
Cleveland, Ohio, 44195
Texas Neurology, PA - Tier 2 Site
Dallas, Texas, 75214
University of Colorado Health Sciences Center - Tier 2 Site
Denver, Colorado, 80262
Duke University Medical Center - Tier 1 Site
Durham, North Carolina, 27705
Pennsylvania State University School of Medicine - Tier 2 Site
Hershey, Pennsylvania, 17033
University of Kansas Medical Center - Tier 2 site
Kansas City, Kansas, 66160
BryanLGH Medical Center - Tier 2 Site
Lincoln, Nebraska, 68506
University of Miami - Tier 2 Site
Miami, Florida, 33136
Medical College of Wisconsin - Tier 2 Site
Milwaukee, Wisconsin, 53226
Vanderbilt University Medical Center - Tier 2
Nashville, Tennessee, 37232-2551
Mount Sinai School of Medicine - Tier 2 Site
New York, New York, 10029
Columbia University Medical Center - Tier 2 site
New York, New York, 10032
University of California Los Angeles - Tier 2 Site
Pacific Palisades, California, 90272
Drexel University College of Medicine - Tier 1 Site
Philadelphia, Pennsylvania, 19107
University of Pittsburgh Medical Center - Tier 2 Site
Pittsburgh, Pennsylvania, 15213
Providence ALS Center - Tier 2 Site
Portland, Oregon, 97213
University of Texas Health Science Center - Tier 2 Site
San Antonio, Texas, 78229-3900
University of California - San Francisco - Tier 2 Site
San Francisco, California, 94117
Virginia Mason Clinic - Tier 2 Site
Seattle, Washington, 98101
Baystate Medical Center - Tier 2 Site
Springfield, Massachusetts, 01199
Saint Louis University, Neuromuscular Div. - Tier 2 Site
St Louis, Missouri, 63110
Washington University - Tier 2 Site
St Louis, Missouri, 63110
SUNY Downstate Medical Center - Tier 1 Site
Syracuse, New York, 13210
Wake Forest University School of Medicine -Tier 2 Site
Winston-Salem, North Carolina, 27157
Canada4 sites
London Health Science Center - Tier 2 Site
London, Ontario, N6A 5A5
Montreal Neurological Institute - Tier 2
Montreal, Quebec, H3A 2B4
University of Toronto, Sunnybrook Health Sciences Centre - Tier 2 Site
Toronto, Ontario, M4N 3M5
University of British Columbia, Gordon and Leslie Diamond Health Care Centre - Tier 2 Site
Vancouver, British Columbia, V5Z 2G9
About this study
Official title: A Multicenter, Double-Blind, Placebo-Controlled, Phase 2b Study to Investigate the Safety and Efficacy of Arimoclomol in Volunteers With Amyotrophic Lateral Sclerosis (ALS)
Arimoclomol is a small molecule that upregulates "molecular chaperones" in cells under stress. Arimoclomol extends survival by five weeks when given both pre-symptomatically and at disease onset in a mutant superoxide dismutase (SOD1) transgenic mouse model of ALS. Furthermore, it has been demonstrated to have neuroprotective and neuroregenerative effects in other rat models of nerve damage. Molecular chaperone proteins are critical in the cellular response to stress and protein misfolding. Recent data suggest that the SOD1 mutation responsible for ALS in some patients with familial disease reduces the availability of a variety of molecular chaperones, and thus weakens their ability to respond to cellular stress. Protein misfolding and consequent aggregation may play a role in the pathogenesis of both the familial and sporadic forms of ALS. Therapeutic agents such as arimoclomol that improve cellular chaperone response to protein misfolding may be helpful in ALS.
Read the detailed description
This is a Phase 2b double-blind, randomized, placebo-controlled parallel-group study evaluating the safety and efficacy of arimoclomol (400 mg t.i.d.) compared to placebo. A safety lead-in phase will be employed to ensure the safety of all study volunteers.
Tier I (Safety Lead-in): During the enrollment period for the safety lead-in phase, 24 volunteers meeting inclusion/exclusion criteria will be randomized at 4 investigative sites. These volunteers will have weekly visits during the first 4 weeks after starting treatment. Pharmacokinetics (PK) will be performed at various timepoints throughout these 4 weeks. After the initial 4 weeks of treatment, visits will continue at 4-week intervals up to Week 36, subsequently visits will occur every 8 weeks up to Week 68. A final visit will occur at Week 72. There will be a 28-day post study medication Follow-Up Telephone Call to assess medical status and adverse events.
Tier II: After the Tier I volunteers finish 4 weeks of treatment, their data will be reviewed by the IDMC and, if no serious safety issues are identified, the recommendation will be made to start the second enrollment period (Tier II). During Tier II enrollment, volunteers recruited from approximately 30 to 40 centers in the US and Canada will be randomized. After screening and randomization, volunteers will be followed every 4 weeks for 9 months. Subsequently visits will occur every 8 weeks up to Week 68, with interim Follow-Up Telephone Calls at Weeks 16, 24, and 32 and a final visit at Week 72. A Week 76 Follow-Up Telephone Call to assess medical status and adverse events will occur at 28 days post last dose of study medication.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Placebo, Arimoclomol
- Keywords
- ALS, Lou Gehrig's disease
- 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.
PlaceboDrug
Placebo t.i.d.
ArimoclomolDrug
capsule, 400 mg t.i.d.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | Not described Receives: Drug: Placebo |
| 2 | Experimental | Not described Receives: Drug: Arimoclomol |
What is being measured
The primary outcome is the main question the study is designed to answer.
ALSFRS-R
Measured: 9 months
Secondary outcomes (6)
ALSFRS-R
Measured: 18 months
Survival
Measured: 18 months
Muscle strength
Measured: 9 and 18 months
Pulmonary function
Measured: 9 and 18 months
MUNE
Measured: 9 and 18 months
Quality of Life
Measured: 9 and 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2007 (estimated)
Why it stopped: Not moving forward with program.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- CytRx
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Merit Cudkowicz, MD, MSc, Principal investigator, Massachusetts General HospitalJeremy Shefner, MD, PhD, Principal investigator, State University of New York - Upstate Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00561366
- Sponsor's protocol ID
- AALS-003
- Status last verified
- Feb 2012
- First submitted
- 16 Nov 2007
- Last updated
- 9 Feb 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Double-Blind, Placebo-Controlled, Phase 2b Study to Investigate the Safety and Efficacy of Arimoclomol in Volunteers With Amyotrophic Lateral Sclerosis (ALS)
- ClinicalTrials.gov ID
- NCT00561366
- Acronym / sponsor ID
- AALS-003
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- ALS, Lou Gehrig's disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Not moving forward with program.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- CytRxIndustry (pharma, biotech, devices)
- First posted
- 20 Nov 2007 (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.
Arimoclomol is a small molecule that upregulates "molecular chaperones" in cells under stress. Arimoclomol extends survival by five weeks when given both pre-symptomatically and at disease onset in a mutant superoxide dismutase (SOD1) transgenic mouse model of ALS. Furthermore, it has been demonstrated to have neuroprotective and neuroregenerative effects in other rat models of nerve damage. Molecular chaperone proteins are critical in the cellular response to stress and protein misfolding. Recent data suggest that the SOD1 mutation responsible for ALS in some patients with familial disease reduces the availability of a variety of molecular chaperones, and thus weakens their ability to respond to cellular stress. Protein misfolding and consequent aggregation may play a role in the pathogenesis of both the familial and sporadic forms of ALS. Therapeutic agents such as arimoclomol that improve cellular chaperone response to protein misfolding may be helpful in ALS.
Detailed description
This is a Phase 2b double-blind, randomized, placebo-controlled parallel-group study evaluating the safety and efficacy of arimoclomol (400 mg t.i.d.) compared to placebo. A safety lead-in phase will be employed to ensure the safety of all study volunteers.
Tier I (Safety Lead-in): During the enrollment period for the safety lead-in phase, 24 volunteers meeting inclusion/exclusion criteria will be randomized at 4 investigative sites. These volunteers will have weekly visits during the first 4 weeks after starting treatment. Pharmacokinetics (PK) will be performed at various timepoints throughout these 4 weeks. After the initial 4 weeks of treatment, visits will continue at 4-week intervals up to Week 36, subsequently visits will occur every 8 weeks up to Week 68. A final visit will occur at Week 72. There will be a 28-day post study medication Follow-Up Telephone Call to assess medical status and adverse events.
Tier II: After the Tier I volunteers finish 4 weeks of treatment, their data will be reviewed by the IDMC and, if no serious safety issues are identified, the recommendation will be made to start the second enrollment period (Tier II). During Tier II enrollment, volunteers recruited from approximately 30 to 40 centers in the US and Canada will be randomized. After screening and randomization, volunteers will be followed every 4 weeks for 9 months. Subsequently visits will occur every 8 weeks up to Week 68, with interim Follow-Up Telephone Calls at Weeks 16, 24, and 32 and a final visit at Week 72. A Week 76 Follow-Up Telephone Call to assess medical status and adverse events will occur at 28 days post last dose of study medication.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Placebo comparator | Drug: Placebo |
| 2 | Experimental | Drug: Arimoclomol |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Familial or sporadic ALS.
- Diagnosed with laboratory-supported probable, probable or definite ALS according to the World Federation of Neurology El Escorial criteria for less than or equal to 36 months' duration prior to the Screening Visit.
- Vital capacity (VC) equal to or greater than 70% predicted value for gender, height and age at the Screening Visit.
- Geographic accessibility to the study site.
- Ability to take oral medication at the Screening Visit, based on verbal report.
Key exclusion criteria (10 listed)
- History of known sensitivity or intolerability to arimoclomol or to any other related compound.
- Prior exposure to arimoclomol through a clinical trial or physician-sponsored IND.
- Exposure to any investigational agent within 30 days of the Screening Visit.
- Presence of any of the following clinical conditions:
- Laboratory values: Screening serum creatinine greater than or equal to 1.5 mg/dL, creatinine clearance less than 70 cc/min, alanine aminotransferase (ALT) greater than 3.0 times the upper limit of normal, total bilirubin greater than 1.5 times the upper limit of normal, white blood cell (WBC) count less than 3,500/mm3, platelet concentration of <100,000/ul, hematocrit level of less than 33 % for female or less than 35 % for male, or coagulation tests (PT, PTT) greater than or equal to 1.5 times upper limit of normal.
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 |
|---|---|---|
| PlaceboPlacebo t.i.d. | Drug | 1 |
| Arimoclomolcapsule, 400 mg t.i.d. | Drug | 2 |
Primary outcome
ALSFRS-R
Time frame: 9 months
6 secondary outcomes
ALSFRS-R
Time frame: 18 months
Survival
Time frame: 18 months
Muscle strength
Time frame: 9 and 18 months
Pulmonary function
Time frame: 9 and 18 months
MUNE
Time frame: 9 and 18 months
Quality of Life
Time frame: 9 and 18 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2012.
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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.
Merit Cudkowicz, MD, MSc principal investigator
Massachusetts General Hospital
Jeremy Shefner, MD, PhD principal investigator
State University of New York - Upstate Medical University
35 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Arimoclomol in people with Amyotrophic Lateral Sclerosis, run by CytRx at 35 sites in 2 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 6 inclusion and 10 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: withdrawn, as of the sponsor's last update on 9 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United States, Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was withdrawn before enrolling participants, so there are no results.
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?
ALSFRS-R (time frame: 9 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Feb 2012.