Rasagiline in Subjects With Amyotrophic Lateral Sclerosis (ALS)

• ClinicalTrials.gov Identifier: NCT01786603
• Recruitment Status: Completed
• First Posted: February 8, 2013
• Results First Posted: January 27, 2020
• Last Update Posted: January 27, 2020
• Sponsor: Richard Barohn, MD
• Information provided by (Responsible Party): Richard Barohn, MD, University of Kansas Medical Center

Tracking Information

• First Submitted Date: November 28, 2012
• First Posted Date: February 8, 2013
• Results First Submitted Date: October 15, 2019
• Results First Posted Date: January 27, 2020
• Last Update Posted Date: January 27, 2020
• Actual Study Start Date: November 21, 2013
• Actual Primary Completion Date: July 27, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 14, 2020)

ALS Functional Rating Scale-Revised (ALSFRS-R) [ Time Frame: ALS Functional Rating Scale-Revised (ALSFRS-R) Difference from Baseline to Month 12 ]

Difference in ALS Functional Rating Scale - Revised (ALSFRS-R) score. The ALSFRS-R is an ordinal rating scale that assesses 12 functional activities. Each activity is scored between 0-4, with a total score ranging from 48 (normal function) to 0 (no function).

Original Primary Outcome Measures (submitted: February 5, 2013)

Change in the ALS Functional Rating Scale-Revised (ALSFRS-R) [ Time Frame: Change from Baseline in ALSFRS-R at 6 months ]

Difference in ALS Functional Rating Scale - Revised (ALSFRS-R) score. The ALSFRS-R is an ordinal rating scale that assesses 12 functional activities. Each activity is scored between 0-4, with a total score ranging from 48 (normal function) to 0 (no function).

Current Secondary Outcome Measures (submitted: January 14, 2020)

• Change in Vital Capacity (VC) [ Time Frame: Vital Capacity Change from Baseline to Month 12 ]
  Determine if decline in vital capacity is slower in participants taking 2 mg rasagiline than controls.
• Change in Quality of Life [ Time Frame: Quality of Life Change from Baseline to Month 12 ]
  Participants completed the single-item ALSQOL (ALS Quality of Life) which asks participants to rank their global quality of life, considering all parts of their lives - physical, emotional, social, spiritual and financial - in the last 7 days and rate on a scale of 0 (very bad) to 10 (excellent).
• Number of Participants With Adverse Events [ Time Frame: Adverse Events from Baseline to Month 12 ]
  Determine if participants on rasagiline 2 mg had a different safety profile than patients not on rasagiline. Adverse event information to be collected from date of enrollment until end of study participation.
• Difference in Survival Status Between Study Groups [ Time Frame: Survival status at Month 12 ]
  Determine if there is a difference in survival between participants on rasagiline than patients not on rasagiline
• Effect of Study Drug on Apoptosis Markers [ Time Frame: Apoptosis Marker change from Baseline to Month 12 ]
  Effect of rasagiline on the apoptosis markers (Annexin V stain) in participants with ALS. Assessed at baseline, month 6, and month 12; change from baseline to month 12 reported. Extra time point was not a pre-specified Primary or Secondary Outcome Measure.
• Effect of Study Drug on Oxidative Stress [ Time Frame: Oxidative Stress change from Baseline to Month 12 ]
  Determine if oxygen radical antioxidant capacity is targeted by rasagiline in participants with ALS. Assessed at baseline, month 6, and month 12; change from baseline to month 12 reported. Extra time point was not a pre-specified Primary or Secondary Outcome Measure.

Original Secondary Outcome Measures (submitted: February 5, 2013)

• Change in vital capacity (VC) [ Time Frame: Change from Baseline in VC at 6 months ]
  Determine if decline in vital capacity is slower in patients taking 2 mg rasagiline than controls.
• Change in quality of life [ Time Frame: Change from Baseline in Quality of Life at 6 months ]
  determine if quality of life improves in patients taking 2 mg rasagiline
• Number of participants with adverse events [ Time Frame: up to 6 months ]
  Determine if patients on rasagiline 2 mg had a different safety profile than patients not on rasagiline. Adverse event information to be collected from date of enrollment until end of study participation.
• Difference in survival status between study groups [ Time Frame: Change from Baseline in survival status at 6 months ]
  Determine if there is a difference in survival between patients on rasagiline than patients not on rasagiline
• Bcl2Bax expression ratio in RNA samples [ Time Frame: up to 6 months ]
  Test to determine if rasagiline targets the Bcl2/Bax expression ration in RNA.
• Biomarker Assays of Mitochondrial Function [ Time Frame: Change from Baseline in Biomarker Assays at 6 months ]
  Determine if rasagiline targets mitochonrial membrane potentials. Effect determined by comparing mean slopes of the study groups.
• Effect of study drug on apoptosis markers [ Time Frame: Change from Baseline in Apoptosis Markers at 6 months ]
  Effect of rasagiline on the apoptosis markers in patients with ALS
• Effect of study drug on oxidative stress [ Time Frame: Change from Baseline in Oxidative Stress at 6 months ]
  Determine if oxiygen radical antioxidant capacity is targeted by rasagiline in patients with ALS.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Rasagiline in Subjects With Amyotrophic Lateral Sclerosis (ALS)
• Official Title: Phase 2 Study of Rasagiline for Treatment of Amyotrophic Lateral Sclerosis

Brief Summary

ALS is a disorder that weakens motor strength and lung function. Rapid loss of motor neurons in the brain and spinal cord of ALS patients causes the symptoms of increasing weakness and loss of muscle function. Motor neurons are responsible for sending signals to muscles in our bodies to trigger movement. While there are drugs to help relieve symptoms of ALS, there is no cure for ALS.

Rasagiline is a drug with possible neuroprotective characteristics. Neuroprotective means that the nervous system may be protected against weakening. It is known that rasagiline has possible neuroprotective characteristics, but the effectiveness of rasagiline for patients with ALS has not been tested. Rasagiline is approved for the treatment of Parkinson's disease.

Rasagiline for treatment of ALS is not approved by the U.S. Food and Drug Administration (FDA) and is investigational. Investigational drugs are studied to find out if they are safe and effective in the treatment of diseases or conditions.

By doing this study, researchers hope to learn if rasagiline is safe and slows disease progression in patients with ALS.

Funding Source - FDA OOPD (FDA Orphan Products Division).

• Detailed Description: The study is a phase II, double-blind, placebo-controlled, multicenter study of rasagiline 2mg/day. Subjects will be assigned to either active agent or placebo (3:1) for twelve months. Subjects will undergo outpatient evaluations at screening, baseline, and months 1, 2, 4, 6, 8, 10 and 12 and telephone assessments at months 3, 5, 7 and 9. There will be a close-out phone call 30 days post month 12.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Amyotrophic Lateral Sclerosis (ALS)

Intervention

• Drug: Rasagiline
  Rasagiline 2mg once a day for 12 months.
  Other Name: Azilect
• Drug: Placebo
  Placebo (looks like study drug but has no active ingredients) once a day for 12 months.

Study Arms

• Experimental: Rasagiline
  Rasagiline 1mg administered orally as a 2mg single dose once daily for 12 months.
  Intervention: Drug: Rasagiline
• Placebo Comparator: Placebo
  Inactive ingredient equal to 1mg rasagiline 2mg administered as a single dose once daily for 12 months.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 5, 2013): 80
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: July 27, 2016
• Actual Primary Completion Date: July 27, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. A clinical diagnosis of laboratory-supported probable, probable, or definite ALS, according to a modified El Escorial criteria, by the study investigator (Appendix IV).
2. 21 to 80 years of age inclusive.
3. VC greater or equal to 75% of predicted at screening and baseline.
4. Onset of weakness within 2 years prior to enrollment.
5. If patients are taking riluzole for ALS, they must be on a stable dose for at least thirty days prior to the baseline visit.
6. Women of childbearing age must be non-lactating and surgically sterile or using an effective method of birth control and have a negative pregnancy test.
7. Willing and able to give signed informed consent that has been approved by the Institutional Review Board (IRB).

Exclusion criteria

1. Requirement for tracheotomy ventilation or non-invasive ventilation for > 23 hours per day.
2. Patients on sympathomimetic agents. This includes pseudoephedrine, phenylephrine, phenylpropanolamine, and ephedrine.
3. Patients on analgesics with serotoninergic properties such as meperidine, tramadol, methadone and propoxyphene, flexeril.
4. Patients on fluoxetine or fluvoxamine.
5. Patients taking amitriptyline > 50 mg/d, trazodone and sertraline > 100 mg/d, citalopram > 20 mg/d or paroxetine > 30 mg/d.
6. Diagnosis of other neurodegenerative diseases (Parkinson disease, Alzheimer disease, etc).
7. Clinically significant history of unstable medical illness (unstable angina, advanced cancer, etc) over the last 30 days.
8. Has a diaphragm pacing device or plan on obtaining a diaphragm pacing device during the course of the study.
9. History of renal disease.
10. History of liver disease.
11. Current pregnancy or lactation.
12. Limited mental capacity such that the patient cannot provide written informed consent or comply with evaluation procedures.
13. History of recent alcohol or drug abuse or noncompliance with treatment or other experimental protocols.
14. Vital Capacity (VC) < 75% of predicted.
15. Receipt of any investigational drug within the past 30 days.
16. Women with the potential to become pregnant who are not practicing effective birth control.
17. Poorly controlled hypertensive subjects or resting systolic blood pressure (SBP) > 160 mmHg and/or diastolic (DBP) > 95 mmHg.
18. Use of BiPAP at screening.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01786603
• Other Study ID Numbers: 12312; R01FD003739 ( U.S. FDA Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Richard Barohn, MD, University of Kansas Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Richard Barohn, MD
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Richard Barohn, MD; University of Kansas Medical Center

• PRS Account: University of Kansas Medical Center
• Verification Date: January 2020