Myasthenia GravisPhase 3IMPACT-MGNCT05919407
Pyridostigmine and Amifampridine for Myasthenia Gravis
A Phase 3 study testing Pyridostigmine and Amifampridine (base) with modified release in people with Myasthenia Gravis, run by Leiden University Medical Center at 1 site in Netherlands.
Trial summary
A randomized, double-blind, placebo controlled, crossover intervention study evaluating the effect of pyridostigmine (part 1) and amifampridine (part 2) in Myasthenia Gravis (MG). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myasthenia Gravis
- What is being tested?
- Pyridostigmine and Amifampridine (base) with modified release
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- 22 Mar 2023to 22 Sep 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >18 years
- AChR positive myasthenia gravis (ocular or generalized)
- Current use of pyridostigmine
- MGFA Clinical Classification I-IV
- Receiving a stable dose of MG treatment (other than pyridostigmine). If applicable:
- A stable steroid regimen for 1 month
Show all 9Show fewer
- Nonsteroidal immunosuppressants: i. Azathioprine, mycophenolate mofetil, cyclosporine or other nonsteroid immunosuppressive agents start > 3 months ago and a stable regimen for 1 month. ii. Rituximab start > 6 months ago, complement inhibitors and Fc receptor inhibitors start > 6 months ago and a stable regimen for 3 months.
- Additional inclusion criteria for part 2 To be eligible for participation in part 2 of the study patients must score >10 points on the MGII questionnaire at inclusion.
- We will include a maximum of 5 patients with a MGFA class I (i.e. 20 percent of the total number of included patients) to ensure that this study accurately reflects the clinical population.
Who cannot join
- Use of intravenous immunoglobulin or plasma exchange <4 weeks or planned during the trial.
- Thymectomy < 6 months, or thymectomy (expected) to take place during the trial
- Use of other acetylcholinesterase inhibitors than pyridostigmine
- Pregnancy, lactation or intention to become pregnant during the study
- Treatment with amifampridine is contraindicated. Contraindications include a history of epilepsy, uncontrolled asthma, inherited QT syndrome / a prolonged QT interval (as indicated by ECG), any drug known to cause QT c-prolongation, any drug known to lower the epileptic threshold, a known hypersensitivity reaction to the active substance or to any of the excipients.
- The patient is unable to fill out the study questionnaires or be interviewed in Dutch, or is unable to undergo the tests needed for the study, or is unable to give informed consent for participation in the study.
- The investigator can exclude patients for this trial which are deemed not suitable for any reason.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Leiden University Medical Center
Leiden, South Holland, 2333 ZA
Martijn R. Tannemaat, MD, PhD, +31 71 5262197, m.r.tannemaat@lumc.nl
About this study
Official title: IMproving Symptomatic Treatment With Pyridostigmine and Amifampridine: a Randomized Double-blinded, Placebo Controlled Crossover Trial in Patients With Myasthenia Gravis (IMPACT-MG)
A randomized, double-blind, placebo controlled, crossover intervention study evaluating the effect of pyridostigmine (part 1) and amifampridine (part 2) in Myasthenia Gravis (MG).
Read the detailed description
In the first part of the study, patients who are currently using pyridostigmine will be randomly allocated to one of two consecutive treatment periods in which patients either first receive placebo and then their usual dose of pyridostigmine, or vice versa. Each treatment period lasts 5 days with a 2-day wash-out period between each treatment period. Measurements will be performed at every last day of a treatment period (day 5 and day 12).
In the second part of the study the effect of two doses of amifampridine as add-on to pyridostigmine will be studied. Patients will be randomly assigned to either one of three treatment sequences; 1) amifampridine 30 mg - amifampridine 60 mg - placebo or 2) amifampridine 60 mg - placebo - amifampridine 30 mg or 3) placebo - amifampridine 30 mg - amifampridine 60 mg. Again, each treatment period consists of 5 days and will be separated by a 2-day wash-out period. Measurements will be performed at every last day of treatment (day 19, day 26 and day 33).
Patients will have the option to participate in a substudy to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of amifampridine in AChR positive MG patients.
- Conditions
- Myasthenia Gravis
- Being tested
- Pyridostigmine, Amifampridine (base) with modified release, Placebo
- Medical subject headings
- Myasthenia Gravis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PyridostigmineDrug
Participants will receive pyridostigmine 10 mg tablets.
Amifampridine (base) with modified releaseDrug
Participants will receive amifampridine (base) with modified release 15 mg or 30 mg tablets.
PlaceboDrug
The placebo tablets will be identical apart from the active substance (pyridostigmine)
PlaceboDrug
The placebo tablets will be identical apart from the active substance (amifampridine base)
| Study group | Role | What they receive |
|---|---|---|
| Pyridostigmine | Experimental | The dose of pyridostigmine will be based on the patient's prior experience with pyridostigmine under the assumption that the patient already gained sufficient experience during their disease course to know which dose is effective for them as patients are advised by their treating neurologist to continually adjust their dose based on their symptoms and side effects. Receives: Drug: Pyridostigmine |
| Placebo (pyridostigmine) | Placebo comparator | Same as "Experimental", however capsules contain placebo. Receives: Drug: Placebo |
| Amifampridine (base) with modified release | Experimental | Patients will receive amifampridine 2 dd 15 mg and amifampridine 2 dd 30 mg as add-on to the pre-study dose of pyridostigmine. Receives: Drug: Amifampridine (base) with modified release |
| Placebo (amifampridine) | Placebo comparator | Same as "Experimental", however capsules contain placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
A clinically relevant change in Myasthenia Gravis Impairment Index (MGII) compared to placebo.
Measured: Assessed on Day 1, Day 5, Day 12, Day 19, Day 26 and Day 33 (cross-over),
Secondary outcomes (16)
Change on 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) compared to placebo
Measured: Assessed on Day 5, Day 12, Day 19, Day 26 and Day 33 (cross-over),
Change on the 15-item revised version of the Myasthenia Gravis Quality of Life questionnaire (MG-QoL15r) compared to placebo
Measured: Assessed on Day 1, Day 5, Day 12, Day 19, Day 26 and Day 33 (cross-over),
A clinically relevant change (≥2 points change) on the Myasthenia Gravis Activities of Daily Living (MG-ADL) score compared to placebo.
Measured: Assessed on Day 1, Day 5, Day 12, Day 19, Day 26 and Day 33 (cross-over),
A clinically relevant change (≥3 points change) on the Quantitative Myasthenia Gravis (QMG) score compared to placebo.
Measured: Assessed on Day 1, Day 5, Day 12, Day 19, Day 26 and Day 33 (cross-over),
Number of patients not able to complete first wash-out period due to an increase in myasthenic symptoms.
Measured: Assessed on Day 1 (crossover)
Number of times escape medication is used (including effect on symptoms)
Measured: Assessed on Day 1, Day 5 and Day 12 (cross-over),
Trough concentrations of pyridostigmine and amifampridine
Measured: Assessed on Day 1, Day 5, Day 12, Day 19, Day 26 and Day 33 (cross-over),
Peak Plasma Concentration (Cmax)
Measured: Assessed on Day 19, Day 26 and Day 33 (cross-over),
Area under the concentration-time curve (AUC0-8)
Measured: Assessed on Day 19, Day 26 and Day 33 (cross-over),
Time of maximum concentration (Tmax)
Measured: Assessed on Day 19, Day 26 and Day 33 (cross-over),
Serum half-life (T1/2)
Measured: Assessed on Day 19, Day 26 and Day 33 (cross-over),
Trough concentration (Ctrough)
Measured: Assessed on Day 19, Day 26 and Day 33 (cross-over),
Dose-response between serum concentrations of amifampridine and hand grip strength as measured with hand-held dynamometer.
Measured: Assessed on Day 19, Day 26 and Day 33 (cross-over),
Utility as assessed by the 5-level EQ-5D (EQ-5D-5L)
Measured: Assessed on Day 1, Day 5, Day 12, Day 19, Day 26 and Day 33
Healthcare use as assessed by the adapted iMCQ (iMTA Medical Consumption Questionnaire)
The iMCQ is adapted by omitting the modules on medication and travel. The recall period for the iMCQ is set to 12 months.
Measured: Assessed on Day 1
Productivity as assessed by the adapted iPCQ (iMTA Productivity Cost Questionnaire)
The recall period for the iPCQ is set to 3 months.
Measured: Assessed on Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2023
- Study start22 Mar 2023
- Primary completion22 Sep 2024 (estimated)
- Study completion22 Sep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Myasthenia GravisStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- NMD Pharma A/S
- Responsible party
- Principal investigator, Martijn R. Tannemaat, MD PhD, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05919407
- Sponsor's protocol ID
- NL78666.058.21
- Acronym
- IMPACT-MG
- Status last verified
- Jun 2023
- First submitted
- 6 Jun 2023
- Last updated
- 26 Jun 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Remijn-Nelissen L, Bakker WR, van den Hout WB, van Gelder T, Ruiter AM, Campman YJM, Badrising UA, Straathof CSM, Verschuuren JJGM, Tannemaat MR. Efficacy of Pyridostigmine in Myasthenia Gravis: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial. Neurology. 2026 Apr 28;106(8):e214865. doi: 10.1212/WNL.0000000000214865. Epub 2026 Apr 7.
PubMed 41945881Remijn-Nelissen L, Bakker WR, van Gelder T, Moes DJAR, Ruiter AM, Campman YJM, Badrising UA, Straathof CSM, Verschuuren JJGM, Tannemaat MR. Efficacy and Safety of Amifampridine in Myasthenia Gravis: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial. Neurology. 2026 Apr 28;106(8):e214715. doi: 10.1212/WNL.0000000000214715. Epub 2026 Apr 7.
PubMed 41945880
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IMproving Symptomatic Treatment With Pyridostigmine and Amifampridine: a Randomized Double-blinded, Placebo Controlled Crossover Trial in Patients With Myasthenia Gravis (IMPACT-MG)
- ClinicalTrials.gov ID
- NCT05919407
- Acronym / sponsor ID
- IMPACT-MG / NL78666.058.21
- Conditions
- Myasthenia Gravis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- NMD Pharma A/S
- Study start
- 22 Mar 2023 (actual)
- Primary completion
- 22 Sep 2024 (estimated)
- Study completion
- 22 Sep 2024 (estimated)
- First posted
- 26 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomized, double-blind, placebo controlled, crossover intervention study evaluating the effect of pyridostigmine (part 1) and amifampridine (part 2) in Myasthenia Gravis (MG).
Detailed description
In the first part of the study, patients who are currently using pyridostigmine will be randomly allocated to one of two consecutive treatment periods in which patients either first receive placebo and then their usual dose of pyridostigmine, or vice versa. Each treatment period lasts 5 days with a 2-day wash-out period between each treatment period. Measurements will be performed at every last day of a treatment period (day 5 and day 12).
In the second part of the study the effect of two doses of amifampridine as add-on to pyridostigmine will be studied. Patients will be randomly assigned to either one of three treatment sequences; 1) amifampridine 30 mg - amifampridine 60 mg - placebo or 2) amifampridine 60 mg - placebo - amifampridine 30 mg or 3) placebo - amifampridine 30 mg - amifampridine 60 mg. Again, each treatment period consists of 5 days and will be separated by a 2-day wash-out period. Measurements will be performed at every last day of treatment (day 19, day 26 and day 33).
Patients will have the option to participate in a substudy to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of amifampridine in AChR positive MG patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Pyridostigmine | Experimental | Drug: PyridostigmineThe dose of pyridostigmine will be based on the patient's prior experience with pyridostigmine under the assumption that the patient already gained sufficient experience during their disease course to know which dose is effective for them as patients are advised by their treating neurologist to continually adjust their dose based on their symptoms and side effects. |
| Placebo (pyridostigmine) | Placebo comparator | Drug: PlaceboSame as "Experimental", however capsules contain placebo. |
| Amifampridine (base) with modified release | Experimental | Drug: Amifampridine (base) with modified releasePatients will receive amifampridine 2 dd 15 mg and amifampridine 2 dd 30 mg as add-on to the pre-study dose of pyridostigmine. |
| Placebo (amifampridine) | Placebo comparator | Drug: PlaceboSame as "Experimental", however capsules contain placebo. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age >18 years
- AChR positive myasthenia gravis (ocular or generalized)
- Current use of pyridostigmine
- MGFA Clinical Classification I-IV
- Receiving a stable dose of MG treatment (other than pyridostigmine). If applicable:
Key exclusion criteria (7 listed)
- Use of intravenous immunoglobulin or plasma exchange <4 weeks or planned during the trial.
- Thymectomy < 6 months, or thymectomy (expected) to take place during the trial
- Use of other acetylcholinesterase inhibitors than pyridostigmine
- Pregnancy, lactation or intention to become pregnant during the study
- Treatment with amifampridine is contraindicated. Contraindications include a history of epilepsy, uncontrolled asthma, inherited QT syndrome / a prolonged QT interval (as indicated by ECG), any drug known to cause QT c-prolongation, any drug known to lower the epileptic threshold, a known hypersensitivity reaction to the active substance or to any of the excipients.
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 |
|---|---|---|
| PyridostigmineParticipants will receive pyridostigmine 10 mg tablets. | Drug | Pyridostigmine |
| Amifampridine (base) with modified releaseParticipants will receive amifampridine (base) with modified release 15 mg or 30 mg tablets. | Drug | Amifampridine (base) with modified release |
| PlaceboThe placebo tablets will be identical apart from the active substance (pyridostigmine) | Drug | Placebo (pyridostigmine) |
| PlaceboThe placebo tablets will be identical apart from the active substance (amifampridine base) | Drug | Placebo (amifampridine) |
Primary outcome
A clinically relevant change in Myasthenia Gravis Impairment Index (MGII) compared to placebo.
Time frame: Assessed on Day 1, Day 5, Day 12, Day 19, Day 26 and Day 33 (cross-over),
16 secondary outcomes
Change on 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) compared to placebo
Time frame: Assessed on Day 5, Day 12, Day 19, Day 26 and Day 33 (cross-over),
Change on the 15-item revised version of the Myasthenia Gravis Quality of Life questionnaire (MG-QoL15r) compared to placebo
Time frame: Assessed on Day 1, Day 5, Day 12, Day 19, Day 26 and Day 33 (cross-over),
A clinically relevant change (≥2 points change) on the Myasthenia Gravis Activities of Daily Living (MG-ADL) score compared to placebo.
Time frame: Assessed on Day 1, Day 5, Day 12, Day 19, Day 26 and Day 33 (cross-over),
A clinically relevant change (≥3 points change) on the Quantitative Myasthenia Gravis (QMG) score compared to placebo.
Time frame: Assessed on Day 1, Day 5, Day 12, Day 19, Day 26 and Day 33 (cross-over),
Number of patients not able to complete first wash-out period due to an increase in myasthenic symptoms.
Time frame: Assessed on Day 1 (crossover)
Number of times escape medication is used (including effect on symptoms)
Time frame: Assessed on Day 1, Day 5 and Day 12 (cross-over),
Trough concentrations of pyridostigmine and amifampridine
Time frame: Assessed on Day 1, Day 5, Day 12, Day 19, Day 26 and Day 33 (cross-over),
Peak Plasma Concentration (Cmax)
Time frame: Assessed on Day 19, Day 26 and Day 33 (cross-over),
Area under the concentration-time curve (AUC0-8)
Time frame: Assessed on Day 19, Day 26 and Day 33 (cross-over),
Time of maximum concentration (Tmax)
Time frame: Assessed on Day 19, Day 26 and Day 33 (cross-over),
Serum half-life (T1/2)
Time frame: Assessed on Day 19, Day 26 and Day 33 (cross-over),
Trough concentration (Ctrough)
Time frame: Assessed on Day 19, Day 26 and Day 33 (cross-over),
Dose-response between serum concentrations of amifampridine and hand grip strength as measured with hand-held dynamometer.
Time frame: Assessed on Day 19, Day 26 and Day 33 (cross-over),
Utility as assessed by the 5-level EQ-5D (EQ-5D-5L)
Time frame: Assessed on Day 1, Day 5, Day 12, Day 19, Day 26 and Day 33
Healthcare use as assessed by the adapted iMCQ (iMTA Medical Consumption Questionnaire)
Time frame: Assessed on Day 1
Productivity as assessed by the adapted iPCQ (iMTA Productivity Cost Questionnaire)
Time frame: Assessed on Day 1
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2023.
- Derived from this study: PubMed 41945881Remijn-Nelissen L, Bakker WR, van den Hout WB, van Gelder T, Ruiter AM, Campman YJM, Badrising UA, Straathof CSM, Verschuuren JJGM, Tannemaat MR. Efficacy of Pyridostigmine in Myasthenia Gravis: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial. Neurology. 2026 Apr 28;106(8):e214865. doi: 10.1212/WNL.0000000000214865. Epub 2026 Apr 7.
- Derived from this study: PubMed 41945880Remijn-Nelissen L, Bakker WR, van Gelder T, Moes DJAR, Ruiter AM, Campman YJM, Badrising UA, Straathof CSM, Verschuuren JJGM, Tannemaat MR. Efficacy and Safety of Amifampridine in Myasthenia Gravis: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial. Neurology. 2026 Apr 28;106(8):e214715. doi: 10.1212/WNL.0000000000214715. Epub 2026 Apr 7.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pyridostigmine and Amifampridine (base) with modified release in people with Myasthenia Gravis, run by Leiden University Medical Center at 1 site in Netherlands.
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 9 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 26 Jun 2023. 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 Netherlands. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Martijn R. Tannemaat, MD, PhD (+31715262197, m.r.tannemaat@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
A clinically relevant change in Myasthenia Gravis Impairment Index (MGII) compared to placebo. (time frame: Assessed on Day 1, Day 5, Day 12, Day 19, Day 26 and Day 33 (cross-over),). 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 NCT05919407, which also lists 2 linked publications.
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 26 Jun 2023.