Evidence map›Paper›PMID 35763114›Full record

Trial reportJournal of neurology2022

Amifampridine safety and efficacy in spinal muscular atrophy ambulatory patients: a randomized, placebo-controlled, crossover phase 2 trial.

Silvia Bonanno, Riccardo Giossi, Riccardo Zanin, Valentina Porcelli, Claudio Iannacone, Giovanni Baranello, Gary Ingenito, Stanley Iyadurai, Zorica Stevic, Stojan Peric and 1 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03781479 (A Randomized, Placebo-Controlled, Crossover Study to Evaluate the Safety and Efficacy of Amifampridine Phosphate in Ambulatory Patients With Spinal Muscular Atrophy), which is not on this map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.8field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03781479 phase2completednot on this map

A Randomized, Placebo-Controlled, Crossover Study to Evaluate the Safety and Efficacy of Amifampridine Phosphate in Ambulatory Patients With Spinal Muscular Atrophy (SMA) Type 3

TypeinterventionalSponsorCatalyst Pharmaceuticals, Inc.Ran2019 to 2020Enrolled13ConditionsMuscular Atrophy, SpinalArmsAmifampridine Phosphate, Placebo Oral Tablet
3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 7 institutions in 4 countries.

Silvia Bonanno *Neuroimmunology and Neuromuscular Disease Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133, Milan, Italy.ORCID http://orcid.org/0000-0002-8823-6821
Riccardo Giossi *Neuroimmunology and Neuromuscular Disease Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133, Milan, Italy.ORCID http://orcid.org/0000-0002-7352-9445
Riccardo ZaninDevelopmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Valentina PorcelliDepartment of Clinical Research and Innovation, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Claudio IannaconeSPARC Consulting, Milan, Italy.
Giovanni BaranelloDevelopmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Gary IngenitoCatalyst Pharmaceuticals, Inc., Coral Gables, USA.
Stanley IyaduraiCatalyst Pharmaceuticals, Inc., Coral Gables, USA.
Zorica StevicFaculty of Medicine, Neurology Clinic, University Clinical Center of Serbia, University of Belgrade, Dr Subotica 6, 11000, Belgrade, Serbia.
Stojan PericFaculty of Medicine, Neurology Clinic, University Clinical Center of Serbia, University of Belgrade, Dr Subotica 6, 11000, Belgrade, Serbia.
Lorenzo MaggiNeuroimmunology and Neuromuscular Disease Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133, Milan, Italy. lorenzo.maggi@istituto-besta.it.ORCID http://orcid.org/0000-0002-0932-5173
Fondazione IRCCS Istituto Neurologico Carlo Besta · ITUniversity of Belgrade · RSCatalyst Pharmaceuticals (United States) · USFIT Consulting (Italy) · ITGreat Ormond Street Hospital · GBJohns Hopkins University · USUniversity of Milan · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSpinal muscular atrophy (SMA) is an autosomal recessive disease where a deficient amount of SMN protein leads to progressive lower motor neuron degeneration. SMN-enhancing therapies are now available. Yet, fatigue and signs of impaired neuromuscular junction (NMJ) transmission could contribute to SMA phenotype. Amifampridine prolongs presynaptic NMJ terminal depolarization, enhancing neuromuscular transmission.

methodsSMA-001 was a phase 2, 1:1 randomized, double-blind, placebo-controlled crossover study. Ambulatory (walking unaided at least 30 m) SMA Type 3 patients, untreated with SMN-enhancing medications, entered a run-in phase where amifampridine was titrated up to an optimized stable dose. Patients achieving at least three points improvement in Hammersmith Functional Motor Score Expanded (HFMSE) were randomized to amifampridine or placebo, alternatively, in the 28-day double-blind crossover phase. Safety was evaluated by adverse events (AE) collection. Primary efficacy measure was the HFMSE change from randomization. Secondary outcomes included timed tests and quality of life assessment. Descriptive analyses and a mixed effects linear model were used for statistics.

resultsFrom 14 January 2019, 13 patients, mean age 34.5 years (range 18-53), with 5/13 (38.5%) females, were included. No serious AE were reported. Transient paresthesia (33.3%) was the only amifampridine-related AE. Six patients for each treatment sequence were randomized. Amifampridine treatment led to a statistically significant improvement in HFMSE (mean difference 0.792; 95% CI from 0.22 to 1.37; p = 0.0083), compared to placebo, but not in secondary outcomes. DISCUSSION: SMA-001 study provided Class II evidence that amifampridine was safe and effective in treating ambulatory SMA type 3 patients. CLINICAL

trial registrationNCT03781479; EUDRACT 2017-004,600-22.

Indexed as

Muscular Atrophy, SpinalSpinal Muscular Atrophies of ChildhoodAmifampridineCross-Over StudiesFemaleHumansMaleQuality of LifeAmifampridine3,4-diaminopyridineAmifampridineFatigueHammersmith functional motor score expandedRandomized controlled trialSpinal muscular atrophy

Identifiers

PMID35763114
PMCPMC9243784
OpenAlexW4283701095

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.