Trial Outcomes & Findings for Controlled Trial to Evaluate Amifampridine Phosphate in Spinal Muscular Atrophy Type 3 Patients (NCT NCT03781479)

Last Updated: 2021-06-01

Results Overview

Hammersmith Functional Motor Scale Expanded (HFMSE) assesses motor function by functional item in order of progressive difficulty, with higher values showing higher function abilities. Each item is scored on a scale of 0-2 with 2 representing item achieved unaided and 0 representing inability to achieve item. Each item was assessed by the patient at Screening, the first (Day 1) and last day (Day 0) of the Run-in period, during Period 1 at Day 7 and Day 14, and during Period 2 at Day 21 and Day 28. The total HFMSE score was calculated as the sum of each item score, with a maximum score of 66 (all items achieved unaided) and minimum score of 0 (all items failed). Change from baseline (CFB) will be assessed from Day 0 to Day 28. A mixed effects liner model was fit with the HFMSE change from baseline (CFB) scores at Day 28 as a response and treatment, sequence, and treatment by sequence as fixed effect terms and patient as a random effect.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

13 participants

Primary outcome timeframe

Screening, the first (Day 1) and last day (Day 0) of the Run-in period, during Period 1 at Day 7 and Day 14, and during Period 2 at Day 21 and Day 28

Results posted on

2021-06-01

Participant Flow

The study was conducted from 14 January 2019 - 17 September 2020 at two sites in Europe.

A screening visit was conducted to ensure that each patient met inclusion/exclusion criteria for the study. Those patients successfully completing screening had procedures/assessments conducted at the start of the Run-in period (Day 1, before starting study medication) and during Run-in, until stable dose and frequency of amifampridine was established for at least 7 days, and at least a 3-point improvement in HFMSE score was achieved from start of Run-in to be eligible for randomization (Day 0).

Participant milestones

Participant milestones
Measure	Amifampridine Phosphate - Placebo Each patient participated in an open-label unblinded drug escalation/treatment run-in phase for up to 4 weeks until stable dose and frequency of amifampridine phosphate was achieved for 7 days. After this phase, half of the subjects were randomized to receive amifampridine in Period 1 and then crossed over to receive placebo in Period 2. Each randomized treatment period was 14 days in duration. Dosing was up to 80 mg per day and frequency was between 3-4 times per day. Amifampridine Phosphate: Amifampridine phosphate tablets 10 mg were provided in round, white-scored tablets, and contained amifampridine phosphate formulated to be the equivalent of 10 mg amifampridine base per tablet. Placebo: A placebo equivalent was provided as tablets indistinguishable from the amifampridine phosphate tablets. The placebo was administered consistent with the dose and dose regimen of amifampridine phosphate.	Placebo - Amifampridine Phosphate Each patient participated in an open-label unblinded drug escalation/treatment run-in phase for up to 4 weeks until stable dose and frequency of amifampridine phosphate was achieved for 7 days. After this phase, half of the subjects were randomized to receive placebo in Period 1 and then crossed over to receive amifampridine in Period 2. Each randomized treatment period was 14 days in duration. Dosing was up to 80 mg per day and frequency was between 3-4 times per day. Placebo: A placebo equivalent was provided as tablets indistinguishable from the amifampridine phosphate tablets. The placebo was administered consistent with the dose and dose regimen of amifampridine phosphate. Amifampridine Phosphate: Amifampridine phosphate tablets 10 mg were provided in round, white-scored tablets, and contained amifampridine phosphate formulated to be the equivalent of 10 mg amifampridine base per tablet.	Not Randomized Patients receiving amifampridine during the open-label run-in period but were not randomized to receive treatment.
Overall Study STARTED	6	6	1
Overall Study COMPLETED	6	6	0
Overall Study NOT COMPLETED	0	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Controlled Trial to Evaluate Amifampridine Phosphate in Spinal Muscular Atrophy Type 3 Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Amifampridine Phosphate - Placebo n=6 Participants Each patient participated in an open-label unblinded drug escalation/treatment run-in phase for up to 4 weeks until stable dose and frequency of amifampridine phosphate was achieved for 7 days. After this phase, half of the subjects were randomized to receive amifampridine in Period 1 and then crossed over to receive placebo in Period 2. Each randomized treatment period was 14 days in duration. Dosing was up to 80 mg per day and frequency was between 3-4 times per day. Amifampridine Phosphate: Amifampridine phosphate tablets 10 mg were provided in round, white-scored tablets, and contained amifampridine phosphate formulated to be the equivalent of 10 mg amifampridine base per tablet. Placebo: A placebo equivalent was provided as tablets indistinguishable from the amifampridine phosphate tablets. The placebo was administered consistent with the dose and dose regimen of amifampridine phosphate.	Placebo - Amifampridine Phosphate n=6 Participants Each patient participated in an open-label unblinded drug escalation/treatment run-in phase for up to 4 weeks until stable dose and frequency of amifampridine phosphate was achieved for 7 days. After this phase, half of the subjects were randomized to receive placebo in Period 1 and then crossed over to receive amifampridine in Period 2. Each randomized treatment period was 14 days in duration. Dosing was up to 80 mg per day and frequency was between 3-4 times per day. Placebo: A placebo equivalent was provided as tablets indistinguishable from the amifampridine phosphate tablets. The placebo was administered consistent with the dose and dose regimen of amifampridine phosphate. Amifampridine Phosphate: Amifampridine phosphate tablets 10 mg were provided in round, white-scored tablets, and contained amifampridine phosphate formulated to be the equivalent of 10 mg amifampridine base per tablet.	Not Randomized n=1 Participants Patients receiving amifampridine during the open-label run-in period but were not randomized to receive treatment.	Total n=13 Participants Total of all reporting groups
Age, Continuous	37.2 years STANDARD_DEVIATION 8.5 • n=5 Participants	30.2 years STANDARD_DEVIATION 13.5 • n=7 Participants	45.0 years n=5 Participants	34.5 years STANDARD_DEVIATION 11.3 • n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	12 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Weight	64.7 kg STANDARD_DEVIATION 9.3 • n=5 Participants	67.8 kg STANDARD_DEVIATION 11.8 • n=7 Participants	76.9 kg n=5 Participants	67.0 kg STANDARD_DEVIATION 10.2 • n=4 Participants
Height	169.3 cm STANDARD_DEVIATION 9.0 • n=5 Participants	174.8 cm STANDARD_DEVIATION 6.1 • n=7 Participants	170.0 cm n=5 Participants	171.9 cm STANDARD_DEVIATION 7.6 • n=4 Participants
BMI	22.5 kg/m^2 STANDARD_DEVIATION 1.4 • n=5 Participants	22.3 kg/m^2 STANDARD_DEVIATION 4.3 • n=7 Participants	26.6 kg/m^2 n=5 Participants	22.7 kg/m^2 STANDARD_DEVIATION 3.1 • n=4 Participants

PRIMARY outcome

Timeframe: Screening, the first (Day 1) and last day (Day 0) of the Run-in period, during Period 1 at Day 7 and Day 14, and during Period 2 at Day 21 and Day 28

Population: The analysis of primary outcome data was based on the Full Analysis Set population, which included all randomized patients who received at least one dose of study medication (amifampridine or placebo) and had at least one post-treatment efficacy assessment. Patients are compared for efficacy according to the treatment to which they were randomized, regardless of the treatment actually received.

Outcome measures

Outcome measures
Measure	Amifampridine Phosphate n=12 Participants Each patient will participate in an open-label unblinded drug escalation/treatment run-in phase for up to 4 weeks until stable dose and frequency of amifampridine phosphate is achieved for 7 days. After this phase, half of the subjects were randomized to receive amifampridine in Period 1 and then crossed over to receive placebo in Period 2 and the other were randomized to receive placebo in Period 1 and then crossed over to receive amifampridine in Period 2. Each randomized treatment period is 14 days in duration. Dosing was up to 80 mg per day and frequency was between 3-4 times per day. Amifampridine Phosphate: Amifampridine phosphate tablets 10 mg were provided in round, white-scored tablets, and contained amifampridine phosphate formulated to be the equivalent of 10 mg amifampridine base per tablet. Placebo: A placebo equivalent was provided as tablets indistinguishable from the amifampridine phosphate tablets. The placebo was administered consistent with the dose and dose regimen of amifampridine phosphate. The Amifampridine study arm includes all patients in the FAS population who received Amifampridine during the treatment period, regardless of which Period the treatment was administered.	Placebo n=12 Participants Each patient will participate in an open-label unblinded drug escalation/treatment run-in phase for up to 4 weeks until stable dose and frequency of amifampridine phosphate is achieved for 7 days. After this phase, half of the subjects were randomized to receive amifampridine in Period 1 and then crossed over to receive placebo in Period 2 and the other were randomized to receive placebo in Period 1 and then crossed over to receive amifampridine in Period 2. Each randomized treatment period is 14 days in duration. Dosing was up to 80 mg per day and frequency was between 3-4 times per day. Amifampridine Phosphate: Amifampridine phosphate tablets 10 mg were provided in round, white-scored tablets, and contained amifampridine phosphate formulated to be the equivalent of 10 mg amifampridine base per tablet. Placebo: A placebo equivalent was provided as tablets indistinguishable from the amifampridine phosphate tablets. The placebo was administered consistent with the dose and dose regimen of amifampridine phosphate. The Placebo study arm includes all patients in the FAS population who received Placebo during the treatment period, regardless of which Period the treatment was administered.
Hammersmith Functional Motor Scale Expanded (HFMSE) Summary Statistics and Mixed Model Analysis	0.208 Overall Score Standard Error 0.326	-0.583 Overall Score Standard Error 0.326

Adverse Events

Amifampridine

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Amifampridine n=12 participants at risk Treatment administered to the patient at the time of onset of the AE.	Placebo n=12 participants at risk Treatment administered to the patient at the time of onset of the AE.
Gastrointestinal disorders Hypoaesthesia oral	8.3% 1/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.	0.00% 0/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.
Gastrointestinal disorders Paraesthesia oral	25.0% 3/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.	0.00% 0/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.
General disorders Fatigue	0.00% 0/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.	8.3% 1/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.
General disorders Gait disturbance	0.00% 0/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.	8.3% 1/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.
General disorders Influenza like illness	8.3% 1/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.	0.00% 0/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.
Infections and infestations Influenza	8.3% 1/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.	0.00% 0/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.
Injury, poisoning and procedural complications Fall	8.3% 1/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.	8.3% 1/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.
Investigations Transaminases increased	8.3% 1/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.	0.00% 0/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.	16.7% 2/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.
Nervous system disorders Headache	8.3% 1/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.	0.00% 0/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.
Nervous system disorders Paraesthesia	8.3% 1/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.	0.00% 0/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.
Respiratory, thoracic and mediastinal disorders Intranasal Paraesthesia	8.3% 1/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.	0.00% 0/12 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continued through four weeks after the last visit or at the early discontinuation visit, for a total of approximately 14 weeks. Non-serious AEs were recorded for each patient after the first administration of study drug through the termination visit or at the early termination visit, for a total of approximately 10 weeks. Serious classification based on the FDA regulatory definition of a serious AE.

Additional Information

Gary Ingenito

Catalyst Pharmaceuticals, Inc.

Phone: 3054203200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place