A Randomized, Placebo-Controlled Study to Evaluate the Effect of Amifampridine in Patients with MuSK Antibody Positive Myasthenia Gravis

Phase 1

• Conditions: Patients with MuSK Antibody Positive Myasthenia Gravis; MedDRA version: 19.1Level: LLTClassification code 10062976Term: Neuromuscular weaknessSystem Organ Class: 100000004859; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2015-003127-62-IT
• Lead Sponsor: FONDAZIONE IRCCS ISTITUTO NEUROLOGICO CARLO BESTA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-03-17
• Last Update Posted: 14 March 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1.Willing and able to provide written informed consent after the nature of the study has been explained and before the start of any research-related procedures.
2.Male or female =18 years of age.
3.Positive serologic test for anti-MuSK antibodies as confirmed at Screening.
4.Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class II to IV at Screening.
5.Myasthenia Gravis Composite (MGC) score equal or greater than 9 points is required at Screening.
6.Need of symptomatic treatment in order to improve muscle performance.
7.Patients undergoing immunosuppressive treatments may be included, but they must remain on stable treatment during the 70-day minimum study period.
8.Patients receiving steroids should not have any modification of drug regimen in the previous month before Screening.
9.Patients receiving immunosuppressive drugs (e.g. azathioprine, cyclophosphamide, methotrexate) should not have any modification of drug regimen in the previous 3 months before Screening.
10.Patients receiving immunomodulatory treatment (e.g. plasma exchange [PE], therapeutic plasma exchange [TPE], intravenous immunoglobulin G [IVIG]) should not have any treatment in the previous 3 weeks before Screening.
11.Female patients of childbearing potential must have a negative pregnancy test (serum human chorionic gonadotropin [HCG]). All patients must practice an effective, reliable and medically approved contraceptive regimen during the study and for up to 5 months following discontinuation of treatment.
12.Ability and availability to participate in the study for at least 70 days based on overall health of the patient and disease prognosis, as applicable, in the opinion of the investigator, and able to comply with all requirements of the protocol, including completion of study questionnaires.

Are the trial subjects under 18? no
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion Criteria

1.Hypersensitivity to the active substance, or to any of the excipients listed.
2.Epilepsy.
3.Uncontrolled asthma.
4.Concomitant use with sultopride.
5.Concomitant use with medicinal products with a narrow therapeutic window.
6.Concomitant use with medicinal products with a known potential to cause QTc prolongation.
7.Patients with congenital QT syndromes.
8. History of thymectomy within 12 months before Screening.
9.Weakness only affecting ocular or peri-ocular muscles (MGFA Class I).
10.MG crisis at Screening (MGFA Class V).
11.An electrocardiogram (ECG) within 6 months before starting treatment that shows clinically significant abnormality(ies), in the opinion of the investigator.
12.Breastfeeding or pregnant at Screening or planning to become pregnant (self or partner) at any time during the study. Male patients with breastfeeding partners are not excluded from the study.
13.Any systemic bacterial or other infection, which is clinically significant in the opinion of the investigator and has not been treated with appropriate antibiotics.
14.Use of PE, TPB, and/or IVIG within 3 weeks before Screening.
15.Use of rituximab within 6 months before Screening.
16.Treatment with an investigational drug (other than amifampridine), device, or biological agent within 30 days before Screening or while participating in this study.
17.Any medical condition that, in the opinion of the investigator, might interfere with the patient’s participation in the study, poses any added risk for the patient, or confounds the assessment of the patients.
18.History of drug allergy to any pyridine-containing substances or any amifampridine excipient(s).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To characterize the overall safety and tolerability of amifampridine compared with placebo in patients with MuSK-MG;Secondary Objective: •To assess the clinical efficacy of amifampridine compared with placebo in patients with MuSK-MG based on improvement in the Myasthenia Gravis Composite (MGC) scale scores.<br>•To assess the clinical efficacy of amifampridine compared with placebo by:<br>oNeurological Institute Carlo Besta-Myasthenia Gravis (NICB-MG) scale; <br>oFatigue measured by Fatigue Severity Scale (FSS);<br>;Primary end point(s): Incidence of TEAEs and SAEs in MuSK-MG patients treated with amifampridine as compared with placebo;;Timepoint(s) of evaluation of this end point: during all treatment

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Difference in MGC of 3 points from baseline; and<br>•Proportion of patients with at least a 3-point reduction in the MGC total score from baseline.<br>•Difference in the NICB-MG total score;<br>•Difference in the FSS mean score;<br>•Difference in the MG-ADL of at least 2 points from baseline;<br>•Difference in the MG-QoL 15 total score; and<br>•Difference in the QMG score.<br>;Timepoint(s) of evaluation of this end point: at the end of the study