16-base single stranded RNA targeting miR-23b linked to oleic acid for Myotonic dystrophy type 1

Inclusion criteria

• {"criterion_text":"- 1. Participant must be 18 to 64 years of age inclusive, at the time of signing the informed consent."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 4. Presence for >3 seconds of grip myotonia (long/middle finger on vHOT) as confirmed by a central reader."}
• {"criterion_text":"- 5. BMI <35 kg/m²."}
• {"criterion_text":"- 6. Male and female participants."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 9. The participant is able to have muscle biopsies as per the Schedule of Activities."}

Exclusion criteria

• {"criterion_text":"- 1. Participants with congenital DM1."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 19. Use of mexiletine or other agent for myotonia within 5 half-lives, prior to screening."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 20. Exposure to another investigational drug within 3 months prior to start of study treatment."}
• {"criterion_text":"- 21. Use of medications which are CCI may be restricted, any use must be discussed and confirmed acceptable with the Medical Monitor"}
• {"criterion_text":"- 3. Medical Research Council Muscle Scale score of ≤ 3 on ankle dorsiflexion (either ankle) or significant tibialis anterior atrophy that prevents a muscle biopsy."}
• {"criterion_text":"- 4. Active COVID-19 infection."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 7. Participants with serum electrolyte abnormalities that cannot be corrected."}
• {"criterion_text":"- 10. Breast cancer within the past 10 years."}
• {"criterion_text":"- 8. Participants receiving concomitant QTc prolonging medications unless on stable doses."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 22. Use of medications which are CCI, including regular use of CCI."}
• {"criterion_text":"- 23. Participants with planned procedures requiring an CCI during the study."}
• {"criterion_text":"- 24. Ongoing participation in any other interventional therapeutic clinical trial."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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: •\tthey have had electrophysiological studies (EPS) within the 2 years prior to screening AND •\ttheir PR interval has remained stable since the EPS (in the opinion of the investigator) AND •\ttheir His-ventricular (HV) interval was ≤ 70ms in the EPS"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 11. ALT or AST > 3.0× upper limit of normal (ULN) at screening."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 13. Known hepatic or biliary abnormalities (except for Gilbert’s syndrome or asymptomatic gallstones)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 15. Recent history (within the past 3 months before Screening) of acute kidney injury."}
• {"criterion_text":"- 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:•\tvalues of > 150 mg per 24 hours are exclusionary •\tvalues 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."}
• {"criterion_text":"- 17. Untreated non-compensated hypothyroidism."}

Primary endpoints

• {"endpoint_text":"- Incidence of Serious Adverse Events (SAEs)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incidence of Adverse Events of Special Interest (AESIs)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incidence of AEs leading to discontinuation of treatment","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incidence of Treatment Emergent Adverse Events (TEAEs)","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Absolute values and changes from baseline in clinical safety laboratory tests and electrocardiogram (ECG) parameters","definition_or_measurement_approach":"Laboratory safety tests and ECG parameter changes from baseline"}
• {"endpoint_text":"- Absolute values and changes from baseline in urine kidney biomarkers (individual and Kidney Safety Composite Measure [KSCM])","definition_or_measurement_approach":"Urine kidney biomarkers measured individually and as Kidney Safety Composite Measure; changes from baseline"}
• {"endpoint_text":"- Absolute values and changes from baseline in vital signs","definition_or_measurement_approach":"Vital sign measurements (e.g., blood pressure, heart rate) and change from baseline"}
• {"endpoint_text":"- Suicidal ideation and behavior assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)","definition_or_measurement_approach":"Assessment using the C-SSRS instrument"}
• {"endpoint_text":"- PK parameters of ATX-01 in plasma (including, but not limited to, area under the curve [AUC], maximum observed plasma concentration [Cmax], time from first dose at which Cmax was apparent [Tmax], apparent elimination half-life [t1/2])","definition_or_measurement_approach":"Plasma pharmacokinetic parameters (AUC, Cmax, Tmax, t1/2, etc.)"}
• {"endpoint_text":"- PK parameters of ATX-01 in urine (including but not limited to amount excreted, CLR, excretion rate)","definition_or_measurement_approach":"Urine pharmacokinetic parameters including amount excreted, renal clearance (CLR), excretion rate"}
• {"endpoint_text":"- PD biomarkers in the tibialis anterior: • Change from baseline in MBNL1 expression (target engagement) • Change from baseline in the RNA Splice Index","definition_or_measurement_approach":"Muscle biopsy PD biomarkers in tibialis anterior measuring change from baseline in MBNL1 expression and RNA Splice Index"}
• {"endpoint_text":"- Change from baseline in video hand opening time (vHOT)","definition_or_measurement_approach":"vHOT measurement from video assessments; change from baseline"}
• {"endpoint_text":"- Change from baseline in ankle dorsiflexion strength by quantitative myometry","definition_or_measurement_approach":"Quantitative myometry of ankle dorsiflexion strength; change from baseline"}
• {"endpoint_text":"- Change from baseline in impact on ADL of myotonia, mobility, upper extremity function, breathing, stamina, GI symptoms (Impact on ADL questionnaire)","definition_or_measurement_approach":"Patient-reported Impact on ADL questionnaire assessing specified domains; change from baseline"}

France

Earliest CTIS Part Ii Submission Date

30-04-2024

Latest Decision Or Authorization Date

12-03-2026

Processing Time Days

681

Number Of Sites

1

Number Of Participants

8

Spain

Earliest CTIS Part Ii Submission Date

25-04-2024

Latest Decision Or Authorization Date

20-02-2026

Processing Time Days

666

Number Of Sites

1

Number Of Participants

8

Italy

Earliest CTIS Part Ii Submission Date

17-06-2024

Latest Decision Or Authorization Date

19-02-2026

Processing Time Days

612

Number Of Sites

2

Number Of Participants

4

Netherlands

Earliest CTIS Part Ii Submission Date

27-05-2025

Latest Decision Or Authorization Date

18-02-2026

Processing Time Days

267

Number Of Sites

1

Number Of Participants

8

Primary sponsor

Full Name

Arthex Biotech S.L.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain

Contract research organisations

Name

Almac Clinical Services Limited

Responsibilities

Packaging and labelling, relabeling, storage and distribution of IMP, ancillary supplies.

Name

Worldwide Clinical Trials

Responsibilities

Vendor Management; Pharmacovigilance; multiple clinical operations responsibilities

Name

Scout Clinical

Responsibilities

Patient reimbursement

Name

Cross Research S.A.

Responsibilities

PK Analysis

Name

Labcorp Early Development Laboratories Limited

Responsibilities

Validation and analysis; PK (blood & urine) assay development

Name

Eresearchtechnology Inc.

Responsibilities

Electronic Clinical Outcome Assess (eCOA); Cardiac Safety (ECG, Holter)

Name

Suvoda LLC

Responsibilities

Responsibilities indicated by code 3 (no descriptive 'value' provided)

Name

Medidata Solutions Inc.

Responsibilities

Responsibilities indicated by code 7 (no descriptive 'value' provided)

Third parties

• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"Packaging and labelling, relabeling, storage and distribution of IMP, ancillary supplies.","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Electronic Clinical Outcome Assess (eCOA)","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Alira Health","duties_or_roles":"Codes with no descriptive 'value' provided (codes: 10; 6)","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Cross Research S.A.","duties_or_roles":"PK Analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Labcorp Early Development Laboratories Limited","duties_or_roles":"validation and analysis; PK (blood & urine) assay development","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"Code 3 (responsibility value not provided)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Croatia","full_name":"Worldwide Clinical Trials","duties_or_roles":"Clinical operations: multiple duties including vendor management; pharmacovigilance; IMP-related responsibilities and others (codes: 1,11,12,15 Vendor Management; 15 Pharmacovigilance; 2; 5; 8).","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Aerverl Medical LLC","duties_or_roles":"Spanish Site equipment - QMA software & hardware","organisation_type":"Industry"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Code 7 (responsibility value not provided)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc. (duplicate entry)","duties_or_roles":"Cardiac Safety (ECG, Holter)","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"IGTP - Instituto de Investigación Germans Trias i Pujol","duties_or_roles":"DNA in blood analysis","organisation_type":"Industry"}
• {"country":"United Kingdom","full_name":"Chillibean Limited","duties_or_roles":"Recording vHOT","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"GenomeScan B.V.","duties_or_roles":"RNA sequencing from RNA extracted from the muscle biopsies","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"France","full_name":"Quipment SAS","duties_or_roles":"Spanish Site equipment - Spirometer, stairs, 9 hole peg test & Infusion pumps and lines","organisation_type":"Industry"}
• {"country":"Germany","full_name":"FyoniBio GmbH","duties_or_roles":"Antidrug antibody assay development; validation and analysis","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Mlm Medical Labs GmbH","duties_or_roles":"Safety labs (blood & urine); Blood store (determination of myostatin levels)","organisation_type":"Laboratory/Research/Testing facility"}