A Multicenter, 18-week Open Label Safety and Efficacy Trial of Dalfampridine in Primary Lateral Sclerosis

Study Purpose:

This study will comprise an 18-week open label safety and tolerability trial. In this study, a total of 35 subjects with primary lateral sclerosis PLS or upper motor neuron predominate ALS will be enrolled. At the initial screening evaluation, a baseline T25FW will be obtained. This baseline test will be repeated at weeks 2, 4, 6, 10, 14 18. The validity of this measure was shown in MS studies when compared to the MSWS-12 (12 item walking scale) and CGI (clinical global impression) scales (35-37). A consistent responder will be defined as improvement in 3 of 4 Timed 25Foot Wwalk while on medication, compared with the baseline results while off medication.

Disease:

Amyotrophic Lateral Sclerosis (ALS),  Familial ALS,  Sporadic ALS, Primary Lateral Sclerosis (PLS)

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:

Enrolling

Phase:

Phase I

Study Chair(s)/Principal Investigator(s):

Dr. Dale J. Lange, Weill Medical College of Cornell University

Clinicaltrials.gov ID (11 digit #):

NCT02868567

Neals Affiliated?

No

Coordinating Center Contact Information

Hospital for Special Surgery
Mona Shahbazi, NP / .(JavaScript must be enabled to view this email address) / 212-774-2361
Shara Holzberg, MS / .(JavaScript must be enabled to view this email address) / 646-797-8592
New York, New York 10021 United States

Full Study Summary:

Study Sponsor:

Weill Medical College of Cornell University

Participant Duration:

18 weeks

Estimated Enrollment:

35

Estimated Study Start Date:

03/01/2016

Estimated Study Completion Date:

01/31/2019

Posting Last Modified Date:

02/26/2018

Date Study Added to alsconsortium.org:

02/26/2018
  • Eligibility Criteria

    Gender:

    Female, Male

    Minimum Age:

    18

    Maximum Age:

    99

    Min Vital Capacity (% predicted normal):

    60

    Time since Symptom Onset:

    Time since Diagnosis:

    Can participants use Riluzole?

    Yes


    Inclusion Criteria:

    Male or female, aged 18-99;
    Diagnosis of upper motor neuron disease, compatible with PLS but may include upper motor neuron (UMN) predominant ALS, defined as only upper motor neuron (UMN) features in at least 2 body regions on examination.
    EMG within 3 months of enrollment with minimal or no evidence of lower motor neuron disease,
    Time from symptom onset > 18 months
    No previous allergy to dalfampradine
    No current or exposure to any therapeutic agent targeting PLS or ALS within 30 days of enrollment.
    Must have a forced vital capacity (FVC) ≥ 60% of expected
    Written informed consent prior to screening is present.
    Subjects on a stable dose of or have not taken Riluzole for at least thirty days
    Impaired walking as measured by a Hauser Index of greater than 1 and less than 7 (2 to 6, inclusive);
    Mini Mental Status Score > 22 and deemed by the PI of being 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 contraception, for example patch or contraceptive ring), intrauterine device (IUD) in place for ≥ 3 months, barrier method in conjunction with spermicide, or another adequate method.
    Elicitable Motor evoked potentials (MEP) recorded at 75% of the stimulator output, using a monophasic, reverse direction, normal current mode pulse.

    Exclusion Criteria:

    History of clinically significant liver disease, renal disease, peripheral neuropathy, serious peripheral vascular disease, known HSP or + C9orf72 or SPG4 mutation, or any other medical condition felt to be exclusionary by the investigator;
    Unwillingness to sign informed consent or any other reasons for which the investigator feels the subject cannot complete the study;
    Women who are pregnant, breastfeeding, or trying to become pregnant;
    Active cancer within the previous 2 years, except treated basal cell carcinoma of the skin;
    Subjects taking any other experimental drugs within 30 days prior to enrollment;
    Patient has any history of seizures; brain surgery, brain implants, any metallic implants above the neck, cardiac pacemakers, cochlear implants, piercing or body modification above the neck, known history of TMS related complications or side-effects, tinnitus.
    Patient has moderate or severe renal impairment as defined by a calculated creatinine clearance of ≤50 mL/minute;
    Patient has been administered botulinum toxin in the lower extremities within 6 months prior to the screening visit and/or is expected to receive botulinum toxin in the lower extremities during the course of the study;
    Patient has a known allergy to pyridine-containing substances or any of the inactive ingredients of the dalfampridine tablet (colloidal silicon dioxide, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide);
    Patient has a history of drug or alcohol abuse within the past year;
    Patient has clinically significant abnormal laboratory values.
    Anything else that, in the opinion of the SI, would place the subject at increased risk or preclude the subject's full compliance with or completion of the study.
    Inability to record an MEP at 75% of the stimulator output using a monophasic, reverse direction, normal current mode pulse due to either an in-excitable motor cortex, co-existing conditions that prevent TMS to be performed in a study subject, inability to tolerate the procedure, or any other cause.

  • Site Contact Information

    Hospital for Special Surgery
    Mona Shahbazi, NP / .(JavaScript must be enabled to view this email address) / 212-774-2361

    New York, New York 10021
    United States