Lambert-Eaton Myasthenic SyndromePhase 3NCT02970162
Phase 3 Study to Evaluate Efficacy of Amifampridine Phosphate in Lambert-Eaton Myasthenic Syndrome (LEMS)
A Phase 3 study testing Amifampridine Phosphate in people with Lambert-Eaton Myasthenic Syndrome, run by Catalyst Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
This study evaluates the effect of withdrawing amifampridine phosphate treatment from patients with LEMS. One half of the patients will continue to receive amifampridine phosphate and the other half will receive placebo, during this double-blind study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lambert-Eaton Myasthenic Syndrome
- 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
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2016to Oct 2017
- Phase
- Phase 3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female ≥18 years of age and currently receiving amifampridine phosphate for LEMS.
- Diagnosis of LEMS by antibody testing or electromyography (EMG).
- Completion of anti-cancer treatment at least 3 months (90 days) prior to Screening.
- If receiving peripherally acting cholinesterase inhibitors (e.g. pyridostigmine), a stable dose of cholinesterase inhibitors is required for at least 7 days prior to randomization and throughout the study.
- If receiving permitted oral immunosuppressants (prednisone or other corticosteroid), a stable dose is required for at least 30 days prior to randomization and throughout the study.
- Female patients of childbearing potential must practice an effective, reliable contraceptive regimen during the study.
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- Able to perform all study procedures and assessments.
- Willing and able to travel to study site and attend all clinic study visits.
- Willing and able to provide written informed consent.
Who cannot join
- Clinically significant long corrected QT (QTc) interval on ECG in previous 12 months.
- Seizure disorder.
- Active brain metastases.
- Unable to ambulate.
- Pregnant or lactating females.
- Any other condition which, in the opinion of the Investigator, might interfere with the patient's participation in the study or confound the assessment of the patient.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 3, Double-Blind, Placebo-controlled, Randomized, Parallel-Group Study to Evaluate the Efficacy and Safety of Amifampridine Phosphate in Patients With Lambert-Eaton Myasthenic Syndrome
This study evaluates the effect of withdrawing amifampridine phosphate treatment from patients with LEMS. One half of the patients will continue to receive amifampridine phosphate and the other half will receive placebo, during this double-blind study.
Read the detailed description
This was a randomized (1:1), double-blind, placebo-controlled, parallel-group, withdrawal study designed to evaluate the efficacy and safety of amifampridine phosphate in patients diagnosed with LEMS. The study was planned to include approximately 28 male and female patients.
Prior to the study, patients were receiving unblinded treatment in the expanded access program (EAP-001). Patients had to be on a stable dose and frequency of amifampridine phosphate for at least 1 week prior to randomization into LMS-003. Screening and randomization (Day 0) may have been into a single visit.
Patients who met eligibility criteria were randomized 1:1 to amifampridine phosphate (at the patient's optimal dose) or placebo on Day 0.
Baseline assessments were obtained on Study Day 0, while the patient has been on open-label amifampridine phosphate and in relationship to the usual dosing schedule. Patients took blinded study medication on Day 1 through Day 3. On Day 4, a dose of blinded study medication was administered by the site study personnel. This was the same medication that the patient took on Day 1 through Day 3. The assessments listed below were performed following either the second, third, or fourth dose of medication taken on Day 4, and this should be the same dose after which Day 0 assessments were performed. For example, if the patient took their second dose of amifampridine in the clinic on Day 0 and had assessments started 40 minutes later, then on Day 4, that patient should be assessed after taking their second dose of investigational product (IP).
Beginning with the next dose after all Day 0 baseline assessments were completed, the patient received IP through Day 4, with a clinic visit on the last day (Day 4) for assessments.
The planned duration of participation for each patient was up to 12 days, including screening (up to 7 days), Day 0 assessments and randomization, and IP administration (Day 1 through Day 4).
- Conditions
- Lambert-Eaton Myasthenic Syndrome
- Being tested
- Amifampridine Phosphate, Placebo Oral Tablet
- Keywords
- LEMS
- Medical subject headings
- Lambert-Eaton Myasthenic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amifampridine PhosphateDrug
Placebo Oral TabletDrug
| Study group | Role | What they receive |
|---|---|---|
| amifampridine phosphate | Experimental | amifampridine phosphate 10 mg (amifampridine equivalent) by mouth, 30 to 80 mg total daily dose, 3 to 4 times per day for 4 days Receives: Drug: Amifampridine Phosphate |
| placebo (for amifampridine phosphate) | Placebo comparator | placebo by mouth 3 to 4 times per day for 4 days Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quantitative Myasthenia Gravis (QMG) Score
The QMG is a physician-rated test including 13 assessments such as facial strength, swallowing, grip strength, and duration of time that limbs can be maintained in outstretched positions. Each assessment is graded as 0 (none), 1 (mild), 2 (moderate), or 3 (severe), for a total range of 0-39. A higher total score indicates a worse outcome.
Measured: change from baseline in QMG score at end of day 4
Subject Global Impression (SGI) Score
The SGI is a 7-point scale on which the patient rates their global impression of the effects of a study treatment (1=terrible to 7=delighted). The SGI was assessed by the patient or the patient's parent/guardian/caregiver if the patient was unable to complete the SGI. The SGI has demonstrated concordance with the physician's assessment of improvement.
Measured: change from baseline in SGI score at end of day 4
Secondary outcomes (1)
Change in Clinician's Global Impression of Improvement (CGI-I) at Day 4 Compared to Baseline
The CGI-I captures the Investigator's global impression of the patient's improvement or worsening from baseline status. The 7-point scale is scored by the Investigator based on changes in symptoms, behavior, and functional abilities. Each symptom is rated as 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), or 7 (very much worse). The total score can range from 0 to 49. A higher score indicates a worse outcome.
Measured: change from baseline in CGI-I score at end of day 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2016 (estimated)
- Study startNov 2016
- Primary completionOct 2017
- Study completionOct 2017
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.
- Other trials for Lambert-Eaton Myasthenic SyndromeStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Catalyst Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Perry Shieh, MD, PhD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02970162
- Sponsor's protocol ID
- LMS-003
- Status last verified
- Dec 2018
- First submitted
- 16 Nov 2016
- Last updated
- 24 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Double-Blind, Placebo-controlled, Randomized, Parallel-Group Study to Evaluate the Efficacy and Safety of Amifampridine Phosphate in Patients With Lambert-Eaton Myasthenic Syndrome
- ClinicalTrials.gov ID
- NCT02970162
- Acronym / sponsor ID
- LMS-003
- Conditions
- Lambert-Eaton Myasthenic Syndrome
- Keywords
- LEMS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Catalyst Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Nov 2016
- Primary completion
- Oct 2017 (actual)
- Study completion
- Oct 2017 (actual)
- First posted
- 21 Nov 2016 (estimated)
- Results
- Posted 24 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the effect of withdrawing amifampridine phosphate treatment from patients with LEMS. One half of the patients will continue to receive amifampridine phosphate and the other half will receive placebo, during this double-blind study.
Detailed description
This was a randomized (1:1), double-blind, placebo-controlled, parallel-group, withdrawal study designed to evaluate the efficacy and safety of amifampridine phosphate in patients diagnosed with LEMS. The study was planned to include approximately 28 male and female patients.
Prior to the study, patients were receiving unblinded treatment in the expanded access program (EAP-001). Patients had to be on a stable dose and frequency of amifampridine phosphate for at least 1 week prior to randomization into LMS-003. Screening and randomization (Day 0) may have been into a single visit.
Patients who met eligibility criteria were randomized 1:1 to amifampridine phosphate (at the patient's optimal dose) or placebo on Day 0.
Baseline assessments were obtained on Study Day 0, while the patient has been on open-label amifampridine phosphate and in relationship to the usual dosing schedule. Patients took blinded study medication on Day 1 through Day 3. On Day 4, a dose of blinded study medication was administered by the site study personnel. This was the same medication that the patient took on Day 1 through Day 3. The assessments listed below were performed following either the second, third, or fourth dose of medication taken on Day 4, and this should be the same dose after which Day 0 assessments were performed. For example, if the patient took their second dose of amifampridine in the clinic on Day 0 and had assessments started 40 minutes later, then on Day 4, that patient should be assessed after taking their second dose of investigational product (IP).
Beginning with the next dose after all Day 0 baseline assessments were completed, the patient received IP through Day 4, with a clinic visit on the last day (Day 4) for assessments.
The planned duration of participation for each patient was up to 12 days, including screening (up to 7 days), Day 0 assessments and randomization, and IP administration (Day 1 through Day 4).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| amifampridine phosphate | Experimental | Drug: Amifampridine Phosphateamifampridine phosphate 10 mg (amifampridine equivalent) by mouth, 30 to 80 mg total daily dose, 3 to 4 times per day for 4 days |
| placebo (for amifampridine phosphate) | Placebo comparator | Drug: Placebo Oral Tabletplacebo by mouth 3 to 4 times per day for 4 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female ≥18 years of age and currently receiving amifampridine phosphate for LEMS.
- Diagnosis of LEMS by antibody testing or electromyography (EMG).
- Completion of anti-cancer treatment at least 3 months (90 days) prior to Screening.
- If receiving peripherally acting cholinesterase inhibitors (e.g. pyridostigmine), a stable dose of cholinesterase inhibitors is required for at least 7 days prior to randomization and throughout the study.
- If receiving permitted oral immunosuppressants (prednisone or other corticosteroid), a stable dose is required for at least 30 days prior to randomization and throughout the study.
Key exclusion criteria (6 listed)
- Clinically significant long corrected QT (QTc) interval on ECG in previous 12 months.
- Seizure disorder.
- Active brain metastases.
- Unable to ambulate.
- Pregnant or lactating females.
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 Phosphate | Drug | amifampridine phosphate |
| Placebo Oral Tablet | Drug | placebo (for amifampridine phosphate) |
Primary outcome
Quantitative Myasthenia Gravis (QMG) Score
Time frame: change from baseline in QMG score at end of day 4
The QMG is a physician-rated test including 13 assessments such as facial strength, swallowing, grip strength, and duration of time that limbs can be maintained in outstretched positions. Each assessment is graded as 0 (none), 1 (mild), 2 (moderate), or 3 (severe), for a total range of 0-39. A higher total score indicates a worse outcome.
Subject Global Impression (SGI) Score
Time frame: change from baseline in SGI score at end of day 4
The SGI is a 7-point scale on which the patient rates their global impression of the effects of a study treatment (1=terrible to 7=delighted). The SGI was assessed by the patient or the patient's parent/guardian/caregiver if the patient was unable to complete the SGI. The SGI has demonstrated concordance with the physician's assessment of improvement.
1 secondary outcome
Change in Clinician's Global Impression of Improvement (CGI-I) at Day 4 Compared to Baseline
Time frame: change from baseline in CGI-I score at end of day 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Perry Shieh, MD, PhD principal investigator
University of California, Los Angeles
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 Amifampridine Phosphate in people with Lambert-Eaton Myasthenic Syndrome, run by Catalyst Pharmaceuticals, Inc. at 1 site in United States.
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 6 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 24 Dec 2018. 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 United States. 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?
Yes. Results are posted in the registry (first posted 24 Dec 2018). 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?
Quantitative Myasthenia Gravis (QMG) Score (time frame: change from baseline in QMG score at end of day 4). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Dec 2018.