An Open-Label, Expanded Access Protocol for Firdapse® (Amifampridine Phosphate; 3,4-Diaminopyridine Phosphate) Treatment in Pediatric Patients With Lambert-Eaton Myasthenic Syndrome (LEMS), and in Pediatric and Adult Patients With Congenital Myasthenic Syndromes (CMSs)

EAP-001

Primary: The primary objective of this study under the original protocol was to provide neuromuscular specialists and neurologists access to amifampridine phosphate therapy for their patients with LEMS, CMS or downbeat nystagmus until the product became commercially available. Secondary: The secondary objective of this study under the original protocol was to provide additional long-term safety data on amifampridine phosphate in patients. Primary The primary objective of this study after its fifth amendment was to provide access to amifampridine phosphate therapy to pediatric patients with LEMS, and pediatric and adult patients with CMS until the product became commercially available for these indications or development of the product for the indication was terminated. Secondary: The secondary objective of this study after its fifth amendment was to assess the long-term safety of amifampridine phosphate in pediatric patients with LEMS, and pediatric and adult patients with CMS.

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Inclusion Criteria - Amendment 5 v6 - most recent version * Male or female: * 2 years of age * Confirmed physician diagnosis of LEMS in pediatric patients or CMS in either pediatric or adult patients. * Completion of anti-cancer treatment at least 3 months (90 days) before treatment. * Negative urine pregnancy test for females of childbearing potential at Screening. * If sexually active and of childbearing potential, willing to use 2 acceptable methods of contraception from screening visit until 3 months after the last dose of investigational product. No adequate clinical data on exposed pregnancies are available for amifampridine. No nonclinical safety data are available regarding the effects of amifampridine on reproductive function. Amifampridine phosphate should not be used during pregnancy. It is unknown whether amifampridine is excreted in human breast milk. The excretion of amifampridine in milk has not been studied in animals. Amifampridine phosphate should not be used during breastfeeding. * Any subject currently participating in study CMS 001 is immediately eligible for enrollment into study EAP-001, as long as inclusion/exclusion criteria are still met. * 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. Exclusion Criteria- Amendment 5 v6 * History of epilepsy and on medication/treatment for the same. * CMS subtypes including slow-channel syndrome, LRP4 deficiency, plectin deficiency and acetylcholinesterase deficiency. * Any subject with a LEMS diagnosis and ≥18 years of age. * Known active brain metastasis. Patients with treated brain metastasis (radiotherapy and/or surgery) who have completed treatment for their brain metastasis \>90 days before Screening, are neurologically stable (neurological symptoms grade \<1), are on a stable dose of corticosteroids and have no evidence of new disease on magnetic resonance imaging (MRI) are eligible, provided they meet the other inclusion/exclusion criteria. * Current use of dalfampridine (Ampyra®; 4-aminopyridine), and any form of 3,4 DAP other than the investigational product provided, such as amifampridine base and does not agree to discontinue use for the duration of the study. * Use of guanidine hydrochloride within 7 days of starting amifampridine phosphate treatment. * History of drug allergy to any pyridine-containing substances or any amifampridine phosphate excipients (i.e. microcrystalline cellulose, colloidal silicon dioxide or calcium stearate). * Use of any other investigational product (other than 3,4 DAP or amifampridine phosphate) or investigational medical device within 30 days before starting treatment or requirement for any investigational agent before completion of all scheduled study assessments. * An electrocardiogram (ECG) within 6 months before starting treatment that shows clinically significant abnormality(ies), in the opinion of the patient's personal physician for pediatric subjects \<18 years of age. * Breastfeeding or pregnant or planning to become pregnant (self or partner). Male patients with breastfeeding partners are not excluded from the study. * Patients with end stage kidney disease on dialysis. * Any condition that, in the view of the Principal Investigator, places the patient at risk, or patients with poor treatment compliance. Inclusion Criteria: Protocol Amendment 1 ( first version IRB approved) * Male or female: * Confirmed genetic diagnosis of CMS. * Negative urine pregnancy test for females of childbearing potential at Screening. * If sexually active and of childbearing potential, willing to use 2 acceptable methods of contraception from screening visit until 3 months after the last dose of investigational product. No adequate clinical data on exposed pregnancies are available for amifampridine. No nonclinical safety data are available regarding the effects of amifampridine on reproductive function. Amifampridine phosphate should not be used during pregnancy. It is unknown whether amifampridine is excreted in human breast milk. The excretion of amifampridine in milk has not been studied in animals. Amifampridine phosphate should not be used during breastfeeding. * 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. Exclusion Criteria: Protocol Amendment 1 ( first version IRB approved) * History of epilepsy and on medication/treatment for the same. * CMS subtypes including slow-channel syndrome, LRP4 deficiency, and acetylcholinesterase deficiency. * Current use of dalfampridine (Ampyra®; 4-aminopyridine), and any form of 3,4 DAP other than the investigational product provided, such as amifampridine base and does not agree to discontinue use for the duration of the study. * Use of guanidine hydrochloride within 7 days of starting amifampridine phosphate treatment. * History of drug allergy to any pyridine-containing substances or any amifampridine phosphate excipients (i.e. microcrystalline cellulose, colloidal silicon dioxide or calcium stearate). * Use of any other investigational product (other than 3,4 DAP or amifampridine phosphate) or investigational medical device within 30 days before starting treatment or requirement for any investigational agent before completion of all scheduled study assessments. * An electrocardiogram (ECG) within 6 months before starting treatment that shows clinically significant abnormality(ies), in the opinion of the patient's personal physician. * Breastfeeding or pregnant or planning to become pregnant (self or partner). Male patients with breastfeeding partners are not excluded from the study. * Any condition that, in the view of the Principal Investigator, places the patient at high risk of poor treatment compliance or of not completing the study.

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2023-09-13