Muscular Atrophy, SpinalPhase 2NCT03781479

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

A Phase 2 study testing Amifampridine Phosphate in people with Muscular Atrophy, Spinal, run by Catalyst Pharmaceuticals, Inc. at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

A two-period, two-treatment, crossover study to evaluate the safety, tolerability and efficacy of amifampridine phosphate in ambulatory patients diagnosed with spinal muscular atrophy (SMA) Type 3. Read more about this study

Who is it for?: Ages 6 to 50 years
Conditions the study is for: Muscular Atrophy, Spinal
What is being tested?: Amifampridine Phosphate
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 13 participants
Where: 1 siteItaly
Study dates: 21 Jan 2019to 23 Jul 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 6 to 50 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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.
Male or female between the ages of 6 and 50 years.
Genetically confirmed diagnosis of SMA Type 3.
Able to walk independently for at least 30 meters.
Not taking Nusinersen for the treatment of SMA (Nusinersen should be stopped at least 6 months before screening). Salbutamol is permitted only if the dose has been stable during the 6 months before screening.
Able to swallow oral medication.
Female patients of childbearing potential must have a negative pregnancy test (serum human chorionic gonadotropin [HCG] at Screening); and must practice an effective, reliable contraceptive regimen during the study and for up to 30 days following discontinuation of treatment.
Ability to participate in the study 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.

Who cannot join

Epilepsy and currently on medication for epilepsy.
Concomitant use of medicinal products with a known potential to cause QTc prolongation.
Patients with long QT syndromes.
An electrocardiogram (ECG) within 6 months before starting treatment that shows clinically significant abnormalities, in the opinion of the Investigator.
Breastfeeding or pregnant at Screening or planning to become pregnant at any time during the study.
Treatment with an investigational drug (other than amifampridine), device, or biological agent within 6 months prior to Screening or while participating in this study.

Show all 10Show fewer

Surgery for scoliosis or joint contractures within the previous 6 months.
Any medical condition that, in the opinion of the Investigator, might interfere with the patient's participation in the study, poses an added risk for the patient, or confound the assessment of the patient.
History of drug allergy to any pyridine-containing substances or any amifampridine excipient(s).
Less than a 3-point improvement in HFSME from start of the Open label Run -in period to end of Run-in (Day 0).

Trial locations and contacts

1 site in 1 country.

Italy1 site

Neurological Institute Carlo Besta
Milan, Lombardy, 20133

Other trials in Italy

About this study

Official title: 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

A two-period, two-treatment, crossover study to evaluate the safety, tolerability and efficacy of amifampridine phosphate in ambulatory patients diagnosed with spinal muscular atrophy (SMA) Type 3.

Read the detailed description

This randomized (1:1), double-blind, placebo-controlled, 2-period, 2-treatment, crossover, outpatient study is designed to evaluate the safety, tolerability and efficacy of amifampridine phosphate in ambulatory patients diagnosed with SMA Type 3. The study is planned to include approximately 12 male and female SMA Type 3 patients. The planned duration of participation for each patient is approximately 2 months, based upon length of dose titration and excluding the screening period, which can last up to 14 days. Patients should only be taking the assigned investigational product (amifampridine phosphate 10 mg tablets or matching placebo tablets), no new therapies are permitted during the study.

Conditions: Muscular Atrophy, Spinal
Being tested: Amifampridine Phosphate, Placebo Oral Tablet
Keywords: Type 3
Medical subject headings: Muscular Atrophy, Spinal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Amifampridine PhosphateDrug
Also called 3,4 diaminopyridine phosphate
Amifampridine phosphate tablets 10 mg will be provided in round, white-scored tablets, and containing amifampridine phosphate formulated to be the equivalent of 10 mg amifampridine base per tablet.
Placebo Oral TabletDrug
Placebo Oral Tablet

Study groups in NCT03781479
Study group	Role	What they receive
Amifampridine Phosphate - Placebo	Experimental	Oral tablets, 30 to 80 mg per day in divided doses 3 to 4 times a day for 4 weeks Receives: Drug: Amifampridine Phosphate; Drug: Placebo Oral Tablet
Placebo - Amifampridine Phosphate	Experimental	Oral tablets, 30 to 80 mg per day in divided doses 3 to 4 times a day for 4 weeks Receives: Drug: Amifampridine Phosphate; Drug: Placebo Oral Tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

Hammersmith Functional Motor Scale Expanded (HFMSE) Summary Statistics and Mixed Model Analysis
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.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Jan 201923 Jul 2020

First posted20 Dec 2018
Study start21 Jan 2019
Primary completion23 Jul 2020
Study completion23 Jul 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Muscular Atrophy, SpinalStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03781479
Sponsor's protocol ID: SMA-001
Status last verified: May 2021
First submitted: 18 Dec 2018
Last updated: 1 Jun 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Bonanno S, Giossi R, Zanin R, Porcelli V, Iannacone C, Baranello G, Ingenito G, Iyadurai S, Stevic Z, Peric S, Maggi L. Amifampridine safety and efficacy in spinal muscular atrophy ambulatory patients: a randomized, placebo-controlled, crossover phase 2 trial. J Neurol. 2022 Nov;269(11):5858-5867. doi: 10.1007/s00415-022-11231-7. Epub 2022 Jun 28.
PubMed 35763114

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 1 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT03781479
Acronym / sponsor ID: SMA-001
Conditions: Muscular Atrophy, Spinal
Keywords: Type 3
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 13 participants (actual)
Lead sponsor: Catalyst Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
Study start: 21 Jan 2019 (actual)
Primary completion: 23 Jul 2020 (actual)
Study completion: 23 Jul 2020 (actual)
First posted: 20 Dec 2018 (actual)
Results: Posted 1 Jun 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

A two-period, two-treatment, crossover study to evaluate the safety, tolerability and efficacy of amifampridine phosphate in ambulatory patients diagnosed with spinal muscular atrophy (SMA) Type 3.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Amifampridine Phosphate - Placebo	Experimental	Drug: Amifampridine Phosphate, Drug: Placebo Oral TabletOral tablets, 30 to 80 mg per day in divided doses 3 to 4 times a day for 4 weeks
Placebo - Amifampridine Phosphate	Experimental	Drug: Amifampridine Phosphate, Drug: Placebo Oral TabletOral tablets, 30 to 80 mg per day in divided doses 3 to 4 times a day for 4 weeks

Who may qualify

Ages: 6 to 50 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (8 listed)

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.
Male or female between the ages of 6 and 50 years.
Genetically confirmed diagnosis of SMA Type 3.
Able to walk independently for at least 30 meters.
Not taking Nusinersen for the treatment of SMA (Nusinersen should be stopped at least 6 months before screening). Salbutamol is permitted only if the dose has been stable during the 6 months before screening.

Key exclusion criteria (10 listed)

Epilepsy and currently on medication for epilepsy.
Concomitant use of medicinal products with a known potential to cause QTc prolongation.
Patients with long QT syndromes.
An electrocardiogram (ECG) within 6 months before starting treatment that shows clinically significant abnormalities, in the opinion of the Investigator.
Breastfeeding or pregnant at Screening or planning to become pregnant at any time during the study.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Amifampridine PhosphateAlso: 3,4 diaminopyridine phosphateAmifampridine phosphate tablets 10 mg will be provided in round, white-scored tablets, and containing amifampridine phosphate formulated to be the equivalent of 10 mg amifampridine base per tablet.	Drug	Amifampridine Phosphate - Placebo, Placebo - Amifampridine Phosphate
Placebo Oral TabletPlacebo Oral Tablet	Drug	Amifampridine Phosphate - Placebo, Placebo - Amifampridine Phosphate

Primary outcome

Hammersmith Functional Motor Scale Expanded (HFMSE) Summary Statistics and Mixed Model Analysis
Time frame: 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
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.

Results and safety

Results posted to the registry on 1 Jun 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Amifampridine Phosphate - Placebo	6	6
Placebo - Amifampridine Phosphate	6	6
Not Randomized	1	0

Primary outcome: Hammersmith Functional Motor Scale Expanded (HFMSE) Summary Statistics and Mixed Model Analysis

Time frame: 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. Least squares mean (Standard Error). Unit: Overall Score

Measure	Amifampridine Phosphate n = 12	Placebo n = 12
Value	0.208 (0.326)	-0.583 (0.326)

Amifampridine Phosphate vs Placebo: Mean Difference (Net): 0.792 (95% CI 0.22 to 1.37), p = 0.0083, Mixed Models Analysis

Population analysed: 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.

Adverse events

Time frame: 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.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Amifampridine	0 of 12 (0%)	5 of 12 (41.7%)	0 of 12
Placebo	0 of 12 (0%)	3 of 12 (25%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35763114Bonanno S, Giossi R, Zanin R, Porcelli V, Iannacone C, Baranello G, Ingenito G, Iyadurai S, Stevic Z, Peric S, Maggi L. Amifampridine safety and efficacy in spinal muscular atrophy ambulatory patients: a randomized, placebo-controlled, crossover phase 2 trial. J Neurol. 2022 Nov;269(11):5858-5867. doi: 10.1007/s00415-022-11231-7. Epub 2022 Jun 28.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Lorenzo Maggi, MD principal investigator

Carlo Besta Institute, Milan, Italy

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Amifampridine Phosphate in people with Muscular Atrophy, Spinal, run by Catalyst Pharmaceuticals, Inc. at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hammersmith Functional Motor Scale Expanded (HFMSE) Summary Statistics and Mixed Model Analysis (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03781479, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2021.