Amyotrophic Lateral SclerosisPhase 2NCT01786174
Gilenya in Amyotrophic Lateral Sclerosis (ALS)
A Phase 2 study testing Gilenya in people with Amyotrophic Lateral Sclerosis, run by Massachusetts General Hospital at 4 sites in United States.
Trial summary
The purpose of this study is to determine whether Gilenya, also known as fingolimod, is safe and tolerable in patients with Amyotrophic 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?
- Gilenya
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 4 sitesUnited States
- Study dates
- Aug 2013to May 2015
- Phase
- Phase 2
- 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
- Age 18 years or older.
- Sporadic or familial ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria (Appendix 1).
- Onset of weakness or spasticity due to ALS ≤ 2 years (24 months) prior to Baseline Visit.
- Slow vital capacity (SVC) measure ≥65% of predicted for gender, height, and age at the screening visit.
- Subjects must not have taken riluzole for at least 30 days, or be on a stable dose of riluzole for at least 30 days, prior to randomization (riluzole-naïve subjects are permitted in the study).
- Subjects must be able to swallow oral medication at the Screening Visit and expected to be able to swallow the capsule throughout the course of the study.
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- Capable of providing informed consent and following trial procedures.
- Geographically accessible to the site.
- Women must not be able to become pregnant (e.g. post menopausal, surgically sterile, or using adequate birth control methods) for the duration of the study and three months after study completion. Adequate contraception includes: abstinence, hormonal contraception (oral contraception, implanted contraception, injected contraception or other hormonal (patch or contraceptive ring, for example) contraception), intrauterine device (IUD) in place for ≥ 3 months, barrier method in conjunction with spermicide, or another adequate method.
- Subjects must agree not to take live attenuated vaccines (including seasonal flu vaccine) 30 days before randomization, throughout the duration of the trial and for 60 days following the trial.
Who cannot join
- Prior use of fingolimod (Gilenya®).
- History or presence of cardiac conditions including:
- Cardiovascular or cerebrovascular disease in the previous 6 months (eg. myocardial infarction, unstable angina, or stroke)
- Congestive heart failure
- First, second- or third-degree atrioventricular block, sick sinus syndrome, or other serious cardiac rhythm disturbances
- Any history of Torsades de Pointes
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- Treatment with a prohibited medication within 30 days of the Baseline Visit:
- Class Ia or III antiarrhythmic medications: i.e., Quinidine, Sotalol Includes Nuedexta b. QT interval prolonging medications c. Ketoconazole d. Beta-blockers e. Calcium channel blockers f. Immunosuppressant medication g. Chemotherapeutic (anti-neoplastic) medications
- Evidence on examination or ECG of bradycardia (<55 bpm), QTc >450ms for women or >430 msec for men, or 1st degree or higher conduction block.
- History of unexplained syncope or cardiac syncope.
- Serum AST and ALT value >2.0 times the upper normal limit.
- Active infection (acute or chronic).
- History of diabetes.
- History of macular edema or uveitis.
- History of lymphopenia.
- History of acquired or inherited immune deficiency syndrome, including leukopenia.
- History of severe untreated chronic obstructive sleep apnea.
- Exposure to any other agent currently under investigation for the treatment of patients with ALS (off-label use or investigational) within 30 days of the Baseline Visit.
- Presence of tracheostomy.
- Use of non-invasive ventilation for hypoventilation due to ALS (such as BiPAP).
- Presence of feeding tube.
- Presence of diaphragmatic pacing system.
- The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair ability of the subject to provide informed consent, according to PI judgment, or a history of active substance abuse within the prior year.
- Clinically significant history of unstable or severe cardiac, oncologic, hepatic, or renal disease, or other medically significant illness.
- Pregnant women or women currently breastfeeding.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Georgia Regents University
Augusta, Georgia, 30912
Massachusetts General Hospital
Boston, Massachusetts, 02114
Methodist Neurological Institute
Houston, Texas, 77030
University of California, Irvine
Orange, California, 92868
About this study
Official title: Phase IIa Double-Blind, Placebo-Controlled Study to Evaluate the Safety of Oral Fingolimod in Patients With Amyotrophic Lateral Sclerosis (ALS)
The purpose of this study is to determine whether Gilenya, also known as fingolimod, is safe and tolerable in patients with Amyotrophic Lateral Sclerosis (ALS).
Read the detailed description
The primary objective of the study is to determine the acute safety and tolerability of oral administration of Gilenya (fingolimod) 0.5mg daily vs. matched oral placebo administered daily.
The primary outcome measure will be safety and tolerability; safety will be assessed by the occurrence of adverse events and clinically meaningful changes in vital signs, ophthalmologic examination, physical examination, electrocardiogram and standard clinical laboratory blood tests, and tolerability will be defined as the ability of subjects to complete the entire 4-week study.
The secondary outcome measure will be the measured effect of the treatment on circulating lymphocyte populations in patients with ALS.
Exploratory outcome measures will include the rate of decline of the ALS Functional Rating Scale (Revised) (ALSFRS-R) and Slow Vital Capacity (VC) during the course of treatment.
This study will be conducted in subjects who meet the El Escorial criteria of possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS. At screening, eligible subjects must be at least 18 years old, must have an SVC ≥ 65% of predicted capacity for age, height and gender, and must provide written informed consent prior to screening. Subjects on a stable dose of riluzole and those not taking riluzole, and women of child-bearing age at screening are eligible for inclusion as long as they meet specific protocol requirements.
Subjects will remain on randomized, placebo-controlled, double-blind treatment until the Week 4 visit. Each randomized subject will also have a Week 8 Follow-up Telephone Interview to assess for adverse events (AEs), changes in concomitant medications and to administer the ALSFRS-R.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Gilenya, Placebo
- Keywords
- ALS, Gilenya, Fingolimod
- 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.
GilenyaDrug
Also called fingolimod
0.5mg Gilenya orally by mouth once daily for approximately 28 days
PlaceboOther
0.5mg placebo (sugar pill) orally by mouth once daily for approximately 28 days
| Study group | Role | What they receive |
|---|---|---|
| Gilenya (fingolimod) | Experimental | 0.5mg Gilenya (fingolimod) orally once daily for 28 days +/- 3 days Receives: Drug: Gilenya |
| Placebo | Placebo comparator | 0.5mg placebo (sugar pill) orally once daily for 28 days +/- 3 days Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
ALSFRS-R Total Score at Weeks 0, 2, 4 and 8
The ALSFRS-R is a quickly administered (5 minutes) ordinal rating scale (ratings 0-4) used to determine subjects' assessment of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Initial validity was established by documenting that in ALS patients, change in ALSFRS-R scores correlated with change in strength over time, was closely associated with quality of life measures, and predicted survival.
Measured: Week 0, Week 2, Week 4 and Week 8
Change in Slow Vital Capacity Score (SVC)
The vital capacity (VC) (percent of predicted normal) was determined using the slow VC method. Vital Capacity is the maximum amount of air a person can expel from the lungs after a maximum inhalation. A subject's VC depends on their age, sex and height. The value is recorded as a percent of predicted normal.
Measured: Week 0, Week 2, Week 4 and Week 8
Forced Expiratory Volume in 1 Second (FEV1)
Forced Expiratory Volume (FEV1): Forced Expiratory Volume (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.
Measured: Screening, Week 0, Week 2, and Week 4
Secondary outcomes (2)
Lymphocyte (T-Cell) Subset Trajectories
Gilenya (fingolimod) has been shown to successfully reduce circulating lymphocytes (a type of white blood cell) by blocking their egress (exit) from the lymph nodes. A secondary objective of the study is to quantify the effect of the treatment on circulating lymphocyte populations in patients with ALS.
Measured: Week 0, Week 2, and Week 4
Forced Expiratory Volume in 1 Second (FEV1) / Slow Vital Capacity (SVC) Ratio
Forced Expiratory Volume (FEV1): Forced Expiratory Volume (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.
Slow Vital Capacity (SVC): Vital Capacity is the maximum amount of air a person can expel from the lungs after a maximum inhalation. A subject's VC depends on their age, sex and height. The value is recorded as a percent of predicted normal.
Measured: Screening, Week 0, Week 2, and Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2013 (estimated)
- Study startAug 2013
- Primary completionSep 2014
- Study completionMay 2015
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.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- ALS Therapy Development Institute
- Responsible party
- Principal investigator, James D. Berry MD, Massachusetts General Hospital
- Investigators
- James D Berry, MD, MPH, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01786174
- Sponsor's protocol ID
- 2013P000313
- Status last verified
- Jun 2016
- First submitted
- 4 Feb 2013
- Last updated
- 1 Jul 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIa Double-Blind, Placebo-Controlled Study to Evaluate the Safety of Oral Fingolimod in Patients With Amyotrophic Lateral Sclerosis (ALS)
- ClinicalTrials.gov ID
- NCT01786174
- Acronym / sponsor ID
- 2013P000313
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- ALS, Gilenya, Fingolimod
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- ALS Therapy Development Institute
- Study start
- Aug 2013
- Primary completion
- Sep 2014 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 7 Feb 2013 (estimated)
- Results
- Posted 31 Dec 2015
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 is to determine whether Gilenya, also known as fingolimod, is safe and tolerable in patients with Amyotrophic Lateral Sclerosis (ALS).
Detailed description
The primary objective of the study is to determine the acute safety and tolerability of oral administration of Gilenya (fingolimod) 0.5mg daily vs. matched oral placebo administered daily.
The primary outcome measure will be safety and tolerability; safety will be assessed by the occurrence of adverse events and clinically meaningful changes in vital signs, ophthalmologic examination, physical examination, electrocardiogram and standard clinical laboratory blood tests, and tolerability will be defined as the ability of subjects to complete the entire 4-week study.
The secondary outcome measure will be the measured effect of the treatment on circulating lymphocyte populations in patients with ALS.
Exploratory outcome measures will include the rate of decline of the ALS Functional Rating Scale (Revised) (ALSFRS-R) and Slow Vital Capacity (VC) during the course of treatment.
This study will be conducted in subjects who meet the El Escorial criteria of possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS. At screening, eligible subjects must be at least 18 years old, must have an SVC ≥ 65% of predicted capacity for age, height and gender, and must provide written informed consent prior to screening. Subjects on a stable dose of riluzole and those not taking riluzole, and women of child-bearing age at screening are eligible for inclusion as long as they meet specific protocol requirements.
Subjects will remain on randomized, placebo-controlled, double-blind treatment until the Week 4 visit. Each randomized subject will also have a Week 8 Follow-up Telephone Interview to assess for adverse events (AEs), changes in concomitant medications and to administer the ALSFRS-R.
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 |
|---|---|---|
| Gilenya (fingolimod) | Experimental | Drug: Gilenya0.5mg Gilenya (fingolimod) orally once daily for 28 days +/- 3 days |
| Placebo | Placebo comparator | Other: Placebo0.5mg placebo (sugar pill) orally once daily for 28 days +/- 3 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age 18 years or older.
- Sporadic or familial ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria (Appendix 1).
- Onset of weakness or spasticity due to ALS ≤ 2 years (24 months) prior to Baseline Visit.
- Slow vital capacity (SVC) measure ≥65% of predicted for gender, height, and age at the screening visit.
- Subjects must not have taken riluzole for at least 30 days, or be on a stable dose of riluzole for at least 30 days, prior to randomization (riluzole-naïve subjects are permitted in the study).
Key exclusion criteria (25 listed)
- Prior use of fingolimod (Gilenya®).
- History or presence of cardiac conditions including:
- Treatment with a prohibited medication within 30 days of the Baseline Visit:
- Evidence on examination or ECG of bradycardia (<55 bpm), QTc >450ms for women or >430 msec for men, or 1st degree or higher conduction block.
- History of unexplained syncope or cardiac syncope.
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 |
|---|---|---|
| GilenyaAlso: fingolimod0.5mg Gilenya orally by mouth once daily for approximately 28 days | Drug | Gilenya (fingolimod) |
| Placebo0.5mg placebo (sugar pill) orally by mouth once daily for approximately 28 days | Other | Placebo |
Primary outcome
ALSFRS-R Total Score at Weeks 0, 2, 4 and 8
Time frame: Week 0, Week 2, Week 4 and Week 8
The ALSFRS-R is a quickly administered (5 minutes) ordinal rating scale (ratings 0-4) used to determine subjects' assessment of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Initial validity was established by documenting that in ALS patients, change in ALSFRS-R scores correlated with change in strength over time, was closely associated with quality of life measures, and predicted survival.
Change in Slow Vital Capacity Score (SVC)
Time frame: Week 0, Week 2, Week 4 and Week 8
The vital capacity (VC) (percent of predicted normal) was determined using the slow VC method. Vital Capacity is the maximum amount of air a person can expel from the lungs after a maximum inhalation. A subject's VC depends on their age, sex and height. The value is recorded as a percent of predicted normal.
Forced Expiratory Volume in 1 Second (FEV1)
Time frame: Screening, Week 0, Week 2, and Week 4
Forced Expiratory Volume (FEV1): Forced Expiratory Volume (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.
2 secondary outcomes
Lymphocyte (T-Cell) Subset Trajectories
Time frame: Week 0, Week 2, and Week 4
Forced Expiratory Volume in 1 Second (FEV1) / Slow Vital Capacity (SVC) Ratio
Time frame: Screening, Week 0, Week 2, and Week 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- ALS Therapy Development Institute (ALS TDI)Link provided by the sponsor.
- Northeast ALS Consortium (NEALS)Link provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
James D Berry, MD, MPH principal investigator
Massachusetts General Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gilenya in people with Amyotrophic Lateral Sclerosis, run by Massachusetts General Hospital at 4 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 10 inclusion and 25 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 1 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 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?
Yes. Results are posted in the registry (first posted 31 Dec 2015). 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?
ALSFRS-R Total Score at Weeks 0, 2, 4 and 8 (time frame: Week 0, Week 2, Week 4 and Week 8). The study lists 3 primary outcomes in all. 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 1 Jul 2016; AzTrials last refreshed its copy on 2 Nov 2026.