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Phase 1/2a study of ATX-01 in participants with DM1
EU CTIS ID: 2023-505363-37-00
What this study is testing
To evaluate the safety and tolerability of ATX-01 in adult participants with DM1
- Human Pharmacology (Phase I)- First administration to humans
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 1. Participant must be 18 to 64 years of age inclusive, at the time of signing the informed consent.
- 10. The participant is able to complete study assessments including all muscle testing assessments without use of assistive devices such as canes, walkers, or orthoses, except for ankle-foot orthoses, or the assistance of another person, at screening and baseline.
- 2. Participants with a documented clinical diagnosis of DM1 (a CTG expansion of >150 repeats in DMPK gene measured in peripheral blood mononuclear cells [PBMCs] would support the clinical diagnosis).
- 3. Ambulatory, defined as able to complete a 10-meter walk/run test (10MWRT) at screening without the use of assistive devices such as canes, walkers, or orthoses, except for ankle-foot orthoses.
- 4. Presence for >3 seconds of grip myotonia (long/middle finger on vHOT) as confirmed by a central reader.
- 5. BMI <35 kg/m².
You likely can't join if
- 1. Participants with congenital DM1.
- 18. Contraindication to a muscle biopsy defined as: use of an anticoagulant (unless it can be temporarily stopped without undue consequence and 5 half-lives passed before the biopsy), platelet count < 50,000, or other bleeding disorder
- 19. Use of mexiletine or other agent for myotonia within 5 half-lives, prior to screening.
- 2. Prior or ongoing medical condition, medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the participant, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.
- 20. Exposure to another investigational drug within 3 months prior to start of study treatment.
- 21. Use of medications which are CCI may be restricted, any use must be discussed and confirmed acceptable with the Medical Monitor
See the full eligibility criteria
Who can join
- 1. Participant must be 18 to 64 years of age inclusive, at the time of signing the informed consent.
- 10. The participant is able to complete study assessments including all muscle testing assessments without use of assistive devices such as canes, walkers, or orthoses, except for ankle-foot orthoses, or the assistance of another person, at screening and baseline.
- 2. Participants with a documented clinical diagnosis of DM1 (a CTG expansion of >150 repeats in DMPK gene measured in peripheral blood mononuclear cells [PBMCs] would support the clinical diagnosis).
- 3. Ambulatory, defined as able to complete a 10-meter walk/run test (10MWRT) at screening without the use of assistive devices such as canes, walkers, or orthoses, except for ankle-foot orthoses.
- 4. Presence for >3 seconds of grip myotonia (long/middle finger on vHOT) as confirmed by a central reader.
- 5. BMI <35 kg/m².
- 6. Male and female participants.
- 7. Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- 8. The participant agrees not to post any personal medical data related to the study or information related to the study on any website or social media (e.g., Facebook, Twitter) or discuss the study publicly until the entire study has been completed.
- 9. The participant is able to have muscle biopsies as per the Schedule of Activities.
What rules you out
- 1. Participants with congenital DM1.
- 18. Contraindication to a muscle biopsy defined as: use of an anticoagulant (unless it can be temporarily stopped without undue consequence and 5 half-lives passed before the biopsy), platelet count < 50,000, or other bleeding disorder
- 19. Use of mexiletine or other agent for myotonia within 5 half-lives, prior to screening.
- 2. Prior or ongoing medical condition, medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the participant, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.
- 20. Exposure to another investigational drug within 3 months prior to start of study treatment.
- 21. Use of medications which are CCI may be restricted, any use must be discussed and confirmed acceptable with the Medical Monitor
- 3. Medical Research Council Muscle Scale score of ≤ 3 on ankle dorsiflexion (either ankle) or significant tibialis anterior atrophy that prevents a muscle biopsy.
- 4. Active COVID-19 infection.
- 5. a. history of pacemaker or implantable cardioverter-defibrillator; participants with pacemakers or implantable cardioverter-defibrillators implanted for solely prophylactic reasons can be included after confirmation from the medical monitor. b. atrial fibrillation or flutter or any other sustained atrial arrhythmia with a resting heart rate (HR) ≥ 100bpm. If a participant is on stable therapy (per the investigator’s judgement), and the participant has a resting HR < 100bpm, the participant can be eligible. c. ventricular tachycardia d. any other sustained ventricular arrhythmia e. undiagnosed syncope in the last year f. congestive heart failure of New York Heart Association (NYHA) functional class IIIV. If a participant with class II-IV is on stable therapy (per investigator’s judgement), participant can be eligible. g. history of myocardial infarction h. congenital heart disease, unless on stable therapy i. moderate or severe valvular heart disease
- 6. Participants with a family history of sudden cardiac death, unexplained death, long QT syndrome, or death from a primary dysrhythmia potentially associated with QT prolongation in any immediate family member (parents, siblings, children) that is not related to an underlying DM1 diagnosis.
- 7. Participants with serum electrolyte abnormalities that cannot be corrected.
- 10. Breast cancer within the past 10 years.
- 8. Participants receiving concomitant QTc prolonging medications unless on stable doses.
- 9. Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
- 22. Use of medications which are CCI, including regular use of CCI.
- 23. Participants with planned procedures requiring an CCI during the study.
- 24. Ongoing participation in any other interventional therapeutic clinical trial.
- 25. Screening systolic blood pressure > 160 mmHg systolic and/or diastolic blood pressure > 100 mmHg. Blood pressure measurements may be repeated up to 3 times if anxiety is thought to be responsible for an elevation of blood pressure.
- 26. Sustained non-sinus rhythm, any second or third degree heart block, PR interval > 240 ms, QRS duration > 120 ms, QTcF > 450 ms (males and females), on a 12-lead ECG at screening (mean or triplicate). Participants with an implantable cardioverter-defibrillators can be enrolled if their PR interval, QRS duration, or QTcF exceed these limits as long as their cardiac ejection fraction on echocardiogram does not meet criteria for exclusion #28.Participants with a PR interval >240ms may be considered eligible if: • they have had electrophysiological studies (EPS) within the 2 years prior to screening AND • their PR interval has remained stable since the EPS (in the opinion of the investigator) AND • their His-ventricular (HV) interval was ≤ 70ms in the EPS
- 27. On a 24-hour ambulatory (Holter) ECG with at least 18 hours of interpretable recordings: any sustained (> 30 seconds) of atrial or ventricular arrhythmias, non- sustained ventricular tachycardia (3 or more beats at > 100 beats per minute [BPM]), Mobitz type II 2nd or 3rd-degree heart block, mean heart rate < 50 BPM in waking hours, any rate pauses > 3.0 seconds in waking hours. For entry into Part 2 (MAD), the 24-hour Holter ECG is required for treatment naïve participants, or if the participant was in the SAD and 6 months have elapsed from the SAD screening Holter assessment.
- 28. Transthoracic Echocardiogram ejection fraction < 45% at Screening or if the participant has had an echocardiogram within the last 6 months. Any moderate or severe abnormality in chamber size, thickness, or valve function. For entry into Part 2 (MAD), if the participant was in the SAD and 6 months have elapsed from the SAD echocardiogram, the echocardiogram is required.
- 29. Participant answers “yes” to C-SSRS suicidal ideation questions 4 or 5 within 1 year before Screening, or any suicidal behavior within 2 years before Screening.
- 11. ALT or AST > 3.0× upper limit of normal (ULN) at screening.
- 12. Total bilirubin > 1.5× ULN at screening (Participants with Gilbert’s syndrome can be included with total bilirubin > 1.5× ULN as long as direct bilirubin is ≤ 1.5× ULN).
- 13. Known hepatic or biliary abnormalities (except for Gilbert’s syndrome or asymptomatic gallstones).
- 14. Chronic renal failure defined as calculated creatine clearance Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation < 60 mL/min/1.73 m² at screening.
- 15. Recent history (within the past 3 months before Screening) of acute kidney injury.
- 16. Proteinuria at screening: a urine protein-to-creatinine ratio (UPCR) ≥ 200 mg/g or a urine albumin-to-creatinine ratio (UACR) > 30 mg/g at screening requires a 24-hour urine collection and measurement of protein excretion:• values of > 150 mg per 24 hours are exclusionary • values between 150 mg to 300 mg can trigger a repeat 24-hour urine measurement of protein excretion at the discretion of the investigator. If the repeat value is also >150 mg, the participant is excluded. Participants with a UPCR of < 200mg/g or a UACR ≤ 30mg/g at screening are eligible without the need for a 24-hour urine protein excretion measurement.
- 17. Untreated non-compensated hypothyroidism.
The study team makes the final eligibility decision.
Where it's taking place
- Canada
- United Kingdom
- United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Canada; United Kingdom; United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.