A phase 1, open-label trial to assess the safety and pharmacokinetics of multiple ascending doses of DT-818 in healthy volunteers and participants with myotonic dystrophy type 1
Myotonic dystrophy (DM1)
DT-818 will be administered in an open-label fashion to healthy participants (Cohort 1) and then to participants with myotonic dystrophy type 1 (DM1, Cohorts 2-6). Each sequential Cohort will receive weekly administrations of DT-818, intravenously or subcutaneously, in a 28-day cycle. The first and 5th doses will require an overnight stay for full PK analysis. Other doses will be administered as an outpatient in the research unit. The dose and subsequent dose escalations will be determined by a safety review committee. DM1 participants will undergo a muscle biopsy before and at the end of treatment to look for the impact of DT-818 on splicing. Total study participation duration is estimated to be approximately four months.
Healthy Volunteers (Cohort 1) 1. Male or female participants, 18–55 years of age, inclusive. 2. Medically healthy with no clinically significant abnormalities based on medical history, physical exam, vital signs, ECG, and clinical laboratory tests at screening. 3. Negative tests for drugs of abuse, alcohol, hepatitis B surface antigen, hepatitis C antibody, and HIV. 4. Willing and able to comply with study restrictions and provide written informed consent. 5. Women of childbearing potential must use highly effective contraception from screening through the end of the study; men must use contraception and refrain from sperm donation for the same period. DM1 Participants (Cohort 2 and beyond) 1. Adults 18–65 years of age with genetically confirmed Myotonic Dystrophy Type 1 (DM1). 2. Stable clinical status and medications for ≥1 month prior to screening. 3. Able and willing to comply with study visits, assessments, and treatment requirements. 4. Provides written informed consent (and caregiver consent, if applicable).
1. History or presence of any clinically significant cardiovascular, hepatic, renal, gastrointestinal, respiratory, hematologic, or neurologic disease (other than DM1 for patient cohorts). 2. Clinically significant ECG findings per protocol defined limits 3. Abnormal laboratory values at screening or per protocol-defined laboratory limits. 4. Participation in another investigational drug or device study within 90 days prior to dosing. 5. Positive test for alcohol or drugs of abuse at screening or admission. 6. Pregnant or breastfeeding women. 7. Any condition that, in the opinion of the investigator, would make the participant unsuitable for the study.