Dalfampridine for ALS

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

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication, ropinirole hydrochloride, to see if it is safe and can be tolerated by patients. It focuses on people with specific motor neuron diseases, PLS or upper motor neuron predominant ALS. The effectiveness of the medication will be measured by checking if patients can walk faster over a short distance.

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.

What data supports the effectiveness of the drug Dalfampridine for ALS?

In a small study, 4-aminopyridine (a component of Dalfampridine) was given to 4 ALS patients, and 2 of them reported improved quality of life, including better facial muscle function and slower disease progression. This suggests potential benefits, but more research is needed to confirm its effectiveness for ALS. ^{1 2 3 4 5}

Is Dalfampridine safe for use in humans?

Dalfampridine, also known as 4-aminopyridine, has been used in clinical trials for multiple sclerosis and other conditions. It is generally safe but may increase the risk of seizures, especially in people with kidney problems. In studies, it was well tolerated with no serious adverse events reported. ^{1 6 7 8 9}

How does the drug Dalfampridine differ from other treatments for ALS?

Dalfampridine is unique because it works by blocking potassium channels in nerve cells, which can help improve nerve signal transmission. This mechanism is different from other ALS treatments that typically focus on reducing inflammation or slowing disease progression. ^{10 11 12 13 14}

Research Team

Dale Lange, MD

Principal Investigator

HSS

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Off-Label Treatment of 4 Amyotrophic Lateral Sclerosis Patients With 4-Aminopyridine. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Assessing dalfampridine efficacy in the physician's office. [2013]

3. England pubmed.ncbi.nlm.nih.gov

The AMPA receptor antagonist perampanel robustly rescues amyotrophic lateral sclerosis (ALS) pathology in sporadic ALS model mice. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. [2022]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Clinical trials for neuroprotection in ALS. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Dalfampridine prior authorization program: a cohort study. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Lack of effect on ambulation of dalfampridine-ER (4-AP) treatment in adult SMA patients. [2021]

8. Japan pubmed.ncbi.nlm.nih.gov

[Perampanel for Sporadic Amyotrophic Lateral Sclerosis]. [2022]

9. Spain pubmed.ncbi.nlm.nih.gov

Dalfampridine in multiple sclerosis. [2017]

10. China pubmed.ncbi.nlm.nih.gov

[Influence of 4-aminopyridine on cell proliferation through inhibiting voltage-gated K+ channel in ovarian cancer]. [2013]

11. Germany pubmed.ncbi.nlm.nih.gov

Activity of the pyrazoloacridines against multidrug-resistant tumor cells. [2019]

12. Poland pubmed.ncbi.nlm.nih.gov

Synthesis and antiproliferative activity in vitro of new 3-substituted aminopyrazolo[3,4-b]pyridines. [2004]

13. England pubmed.ncbi.nlm.nih.gov

1H-Pyrazolo[3,4-b]pyridine inhibitors of cyclin-dependent kinases. [2021]

14. United States pubmed.ncbi.nlm.nih.gov

N4-(omega-Aminoalkyl)-1-[(omega-aminoalkyl)amino]-4- acridinecarboxamides: novel, potent, cytotoxic, and DNA-binding agents. [2019]