Study of Pyridostigmine With Ondansetron in Subjects With Anti-AchR Positive Myasthenia Gravis

A Phase II, Study to Evaluate the Safety and Tolerability of Pyridostigmine When Given With Ondansetron to Subjects With Anti-AchR Positive Myasthenia Gravis

This is a phase II, single center, randomized, double-blind, placebo-controlled, study in patients with a diagnosis of anti-AchR antibody positive myasthenia gravis.

Study Overview

• Status: Recruiting
• Conditions: Myasthenia Gravis
• Intervention / Treatment: Drug: DAS-001

Detailed Description

Methodology: This is a phase II, single center, randomized, double-blind, placebo-controlled, study in patients with a diagnosis of anti-AchR antibody positive myasthenia gravis.

Study Design: The clinical trial will be conducted over a 6-week treatment period.

• Group A: Patients currently taking pyridostigmine and experiencing pyridostigmine-related gastrointestinal (GI) adverse events (AEs) within the past 7 days
• Group B: Patients not currently taking pyridostigmine due to GI AEs or that had their dose reduced due to pyridostigmine related GI AEs Group A will be enrolled in the study and randomized to either the control (pyridostigmine+ placebo) or the test group (pyridostigmine + ondansetron) and treated for 6 weeks. Following enrolment, patients may (if needed) titrate up their pyridostigmine dose at the investigator's discretion each week to the highest dose deemed appropriate, tolerable and safe by the Investigator.

Group B patients not currently taking pyridostigmine due to GI AEs will initiate pyridostigmine at a dose determined by the investigator based on the patient's history and may titrate as deemed tolerable and safe by Investigator during screening; patients on a reduced dose due to pyridostigmine related GI AEs may titrate pyridostigmine as deemed tolerable and safe by the investigator during screening. If patients in Group B experience GI AEs that fulfil enrolment criteria, along with all other inclusion/exclusion criteria, they will be enrolled into the study at that dose and randomized to either the control (pyridostigmine+ placebo) or the test group (pyridostigmine + ondansetron) and treated for 6 weeks. Following enrolment, patients may (if needed) titrate up their pyridostigmine dose at the investigator's discretion each week to the highest dose deemed appropriate, tolerable and safe by the Investigator.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Martine Francis, BA; Phone Number: 301-343-8894; Email: martine@mafinc.com
• Study Contact Backup: Name: Christina Smith, PhD; Phone Number: 609-203-1816; Email: csmith@dastherapeutics.com

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • Recruiting
      • George Washinton University
      • Contact: Radwa Aly, M.Sc; Phone Number: 202-677-6209; Email: raly@mfa.gwu.edu
      • Principal Investigator: Henry Kaminiski, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. diagnosed with myasthenia gravis and who are currently taking pyridostigmine and experienced pyridostigmine-related GI side effects within the past 7 days.
2. GSRS rating of at least Moderate discomfort on questions 5, 11, and 12.
3. Subjects must be willing and able to complete a GI symptom diary within a consistent timeframe on a daily basis.
4. Subjects must be able to tolerate a pyridostigmine dose of 30mg TID.
5. Must be clinically stable in judgement of treating neurologists for past 3 months.
6. Must have AchR antibody positive MG.
7. Subjects must be able to swallow liquids.
8. Subjects must be in good health as determined by their medical history, physical examination, vital signs, and laboratory tests. A subject with a medical abnormality may be included only if the investigator or designee considers that the abnormality will not introduce significant additional risk to the subject's health or interfere with study objectives.
9. Subjects must have signed an informed consent form indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study and comply with the study procedures and restrictions.

Exclusion Criteria:

Key exclusion criteria:

The criteria for exclusion of a subject from enrollment in the study are as follows:

1. Any acute or chronic diseases which are associated with GI distress (such as nausea, vomiting, or diarrhea), which could interfere with the subjects' safety during the trial, expose them to undue risk, or interfere with the study objectives.
2. History or presence of hepatic, or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
3. History of substance abuse, known drug addiction, or positive test for drugs of abuse or alcohol.
4. Patients currently using marijuana for any reason (medical or recreational).
5. Known hypersensitivity to pyridostigmine, or to ondansetron or similar 5-HT3 serotonin receptor antagonists.
6. ECG changes including QT interval prolongation and congenital long QT syndrome. Electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, bradyarrhythmia's or other medicinal products that lead to QT prolongation.
7. Treatment with drugs affecting peripheral cholinergic transmission within 1 month of study entry (with the exception of pyridostigmine).
8. Subjects unlikely to co-operate during the study, and/or be questionably compliant in the opinion of the investigator.
9. Patients currently being treated with narcotics.
10. Patients being treated with aminoglycoside antibiotics, which are contraindicated in myasthenia gravis.
11. Patients unable to be contacted in case of an emergency.
12. Intake of an investigational drug within 30 days of study entry.
13. Pregnancy and women of childbearing potential not willing to follow the birth control requirements as described in the informed consent or breastfeeding.
14. History or presence of obstructive pulmonary disease or urinary obstruction (contraindication for pyridostigmine).
15. This use of selective serotonin reuptake inhibitors (SSRI's).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: treatment; ondansetron + pyridostigmine	Drug: DAS-001; ondansetron + pyridostigmine
Placebo Comparator: Placebo; placebo+ pyridostigmine	Drug: DAS-001; ondansetron + pyridostigmine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with change in the gastrointestinal (GI) side effects	difference in GI side effects as measured by the GSRS-self (Gastrointestinal System Rating Scale - self-administered)	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with change in the side effects	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0" . Incidence and nature of adverse events	6 weeks
Number of participants with change in in physical examine	physical examination changes General appearance,Head, eyes, ears, nose, and throat, Respiratory, Cardiovascular, Musculoskeletal, Abdomen, Neurologic, Extremities, Dermatologic, Lymphatic)	6 weeks
Number of participants with change in in clinical laboratory evaluations	changes in clinical laboratory evaluations (Creatinine, Potassium(K+),Sodium (Na+) , Chloride (Cl-), Magnesium (Mg++), Calcium, Inorganic phosphate, Glucose, Urea,Bilirubin (Total) ,Bilirubin (direct), AST, ALT, GGT, Alkaline phosphatase, Total Protein, Albumin,Hematocrit Hemoglobin Platelet count Red blood cell (RBC) count WBC count WBC differential Mean cell volume (MCV) Mean cell hemoglobin (MCH) MCH concentration (MCHC)	6 weeks
Number of participants with change in Electrocardiography (ECG)	ECG (standard digital 12-lead in singlicate)	6 weeks
Plasma concentrations of pyridostigmine	Cmax	6 weeks
Plasma concentrations of ondansetron	Cmax	6 weeks

Collaborators and Investigators

• Sponsor: DAS-MG, Inc

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2021
• Primary Completion (Anticipated): April 30, 2023
• Study Completion (Anticipated): April 30, 2023

Study Registration Dates

• First Submitted: January 9, 2020
• First Submitted That Met QC Criteria: January 9, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 22, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis
• Other Study ID Numbers: DAS-001-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No