Dalfampridine for ALS

Not currently recruiting at 3 trial locations

Overseen By Mona Shahbazi, NP

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Weill Medical College of Cornell University

Must not be taking: Experimental drugs

Disqualifiers: Liver disease, Renal disease, Cancer, Seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and tolerability of dalfampridine, a treatment under exploration for people with certain forms of ALS, a nervous system disease that weakens muscles. The focus is on improving walking abilities in individuals with upper motor neuron diseases like primary lateral sclerosis (PLS) or ALS that primarily affects the upper motor neurons. The study is open to those who have experienced symptoms for over 18 months, have difficulty walking, and have not used any PLS or ALS treatments in the last 30 days. Participants will take dalfampridine and have their walking speed measured multiple times to assess improvement. For those dealing with upper motor neuron symptoms and walking challenges, this trial could be suitable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you have not taken any therapeutic agent targeting PLS or ALS within 30 days of enrollment. If you are on Riluzole, you must be on a stable dose or have not taken it for at least thirty days before joining the study.

Is there any evidence suggesting that Dalfampridine is likely to be safe for humans?

Research shows that dalfampridine, the treatment under study, has been used in other conditions, providing some safety information. In past studies, over 2% of patients experienced side effects such as urinary tract infections, trouble sleeping, and dizziness. These side effects occurred more frequently than in those who took a placebo (a harmless pill used for comparison).

Dalfampridine is already approved for use in multiple sclerosis (MS), suggesting it might be safe for other conditions. However, this study is in the early stages of research specifically for ALS, so researchers are still gathering safety information. For those considering joining the trial, this means that while some safety information exists, more evidence is being collected specifically for ALS patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for ALS, like Riluzole and Edaravone, focus on slowing disease progression or managing symptoms. Dalfampridine is unique because it targets nerve signal conduction, which is a different approach from existing options. Researchers are excited about Dalfampridine because it has the potential to improve muscle function by enhancing nerve signal strength, offering a new avenue for improving quality of life in ALS patients.

What evidence suggests that Dalfampridine might be an effective treatment for ALS?

Research has shown that dalfampridine can help people walk faster. In studies with multiple sclerosis (MS) patients, more than one-third experienced a 25% increase in walking speed. This trial will evaluate dalfampridine, also known as Ampyra, for its potential benefits in people with ALS (amyotrophic lateral sclerosis). Dalfampridine blocks potassium channels, which may help nerve signals move more effectively. Although less evidence exists for its use in ALS, some reports suggest it can improve quality of life and slow disease progression in certain cases. Overall, the data appears promising for improving movement in diseases like ALS. ^{1 3 4 6 7}

Who Is on the Research Team?

Dale Lange, MD

Principal Investigator

HSS

Are You a Good Fit for This Trial?

This trial is for adults aged 18-99 with primary lateral sclerosis (PLS) or upper motor neuron predominant ALS. Participants must have stable walking impairment, no severe allergies to dalfampridine, and a forced vital capacity over 60%. Women must use effective birth control. Exclusions include pregnancy, recent experimental drug use, certain medical conditions like liver disease or seizures, and metal implants above the neck.

Inclusion Criteria

I have a condition affecting my brain's nerve cells, showing symptoms in at least 2 body areas.

I am mentally capable of understanding and following the trial's procedures.

I haven't taken any drugs for PLS or ALS in the last 30 days.

Exclusion Criteria

I have had active cancer in the last 2 years, except for treated skin cancer.

I have a history of seizures or any metal implants above the neck.

I am willing and able to sign the informed consent.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Dalfampridine in an open-label format for safety and efficacy evaluation

18 weeks

Visits at weeks 2, 4, 6, 10, 14, 18 (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dalfampridine

Trial Overview The study tests the safety and effectiveness of dalfampridine in improving walking speed in PLS/ALS patients over an 18-week period. It involves repeated timed walks to measure any improvement while on medication compared to baseline performance without medication.

How Is the Trial Designed?

Group I: Ampyra Experimental Treatment 1 Intervention

Ampyra open label

Dalfampridine is already approved in United States, European Union for the following indications:

Approved in United States as Ampyra for:

• Improvement of walking in adults with multiple sclerosis

Approved in European Union as Fampyra for:

• Improvement of walking in adults with multiple sclerosis

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Hospital for Special Surgery, New York

Lead Sponsor

Trials

257

Recruited

61,800+

Published Research Related to This Trial

In a phase III trial involving 301 patients with multiple sclerosis, fampridine significantly improved walking ability, with 35% of patients showing a positive response compared to only 8% in the placebo group.

The improvement in walking speed for fampridine-treated patients was substantial at 25.2%, and this was linked to a meaningful reduction in reported ambulatory disability, indicating its efficacy as a treatment for motor function deficits in multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Goodman, AD., Brown, TR., Krupp, LB., et al.[2022]

Dalfampridine, a potassium channel blocker, has been shown to significantly improve walking speed by an average of 25% in over one-third of multiple sclerosis patients in recent phase II and III clinical trials.

While dalfampridine is effective in enhancing mobility, it carries a risk of epileptic seizures as a potential adverse effect, highlighting the importance of monitoring patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dalfampridine in multiple sclerosis. Goodman, AD., Hyland, M.[2017]

Dalfampridine has been shown to improve walking speed in individuals with multiple sclerosis based on three recent randomized controlled trials, indicating its potential efficacy as a treatment.

However, the effectiveness of dalfampridine varies among patients, and there is currently no clear method to identify which patients will benefit significantly from the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing dalfampridine efficacy in the physician's office. Raffel, JB., Malik, O., Nicholas, RS.[2013]

The implementation of a prior authorization (PA) program for dalfampridine in patients with multiple sclerosis led to a significant reduction in utilization, with PA members averaging 2.1 fewer claims per member compared to those without PA, indicating improved safety in prescribing practices.

The PA program resulted in a total cost avoidance of $143,010, suggesting that it not only enhances patient safety by ensuring appropriate use but also reduces overall pharmacy expenditures for dalfampridine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dalfampridine prior authorization program: a cohort study. Gleason, PP., Phillips, J., Fenrick, BA., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02868567

Use of Dalfampridine in Primary Lateral Sclerosis A consistent responder will be defined as improvement in 3 of 4 Timed 25Foot Walk while on medication, compared with the baseline results while off medication.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7931640/

Neuroprotective Properties of 4-Aminopyridine - PMC To evaluate the long-term efficacy and safety of SR-4-AP, the confirmatory ENHANCE study (10 mg twice daily in 646 MS patients) was performed.

3. withpower.com withpower.com/trial/phase-1-motor-neuron-disease-2-2016-c9bab

Dalfampridine for ALS · Info for Participants Dalfampridine, a potassium channel blocker, has been shown to significantly improve walking speed by an average of 25% in over one-third of multiple sclerosis ...

4. researchgate.net researchgate.net/publication/332781130_Off-Label_Treatment_of_4_Amyotrophic_Lateral_Sclerosis_Patients_With_4-Aminopyridine

Off‐Label Treatment of 4 Amyotrophic Lateral Sclerosis ... The 4-Aminopyridine has been reported to be effective in two ALS patients; it improved quality of life and decreased disease progression rate [ ...

5. ampyra-hcp.com ampyra-hcp.com/clinical-trials/

Clinical Study Results AMPYRA® (dalfampridine) improved walking speed in significantly more patients than placebo in 2 clinical studies. · 25%. Average increase in walking speed ...

6. ampyra-hcp.com ampyra-hcp.com/safety-results/

Safety and Tolerability Profile Adverse reactions in ≥2% of patients treated with AMPYRA® (dalfampridine) and more frequently than in placebo-treated patients in controlled clinical studies ...

7. ampyra.com ampyra.com/app/themes/ampyra/pdf/prescribing-information.pdf

prescribing-information.pdf The most common adverse events (incidence ≥2% and at a rate greater than the placebo rate) for AMPYRA were urinary tract infection, insomnia, dizziness, ...