Table 1 Feedback on key considerations for trial selection, protocol elements, and study visits

Considerations for enrollment in clinical trials

• The DM1 and DMD communities are willing to participate in trials because of the significant need for therapies

Advisory participants were supportive of efforts to reduce the considerable travel burden for participants and families:

 • The proximity of the trial site to the home is attractive; car and train travel are significantly preferred over air travel

 • A low frequency of clinic visits/clinic site travel is preferred

Advisory participants were supportive of the following:

 • A shorter placebo duration and asymmetrical study design (2:1 or 3:1) are preferable

 • Input and support from medical care providers and other families living with disease to help make trial participation decisions

 • Patient advocacy organization communication to create visibility and access to trial information is important to support decision making

 • Access to thorough trial inclusion/exclusion criteria to help make initial eligibility determinations and trial assessments easier

Trial participation decisions were positively impacted by the following:

 • An understanding of the investigational medicines’ mechanisms of action

 • An understanding of relevant, non-clinical, translational data

 • A clear explanation of the study design and outcomes

 • The opportunity to receive the active drug in an open-label extension of the study

Clinical trial protocol elements (DMD advisory workshop participants and duchenne CAB feedback)

• Care providers primarily valued functional assessments that measure improvements in the ability to perform an activity; they also prefer video assessments

Advisory participants:

 • Helped Dyne identify appropriate measures to mitigate anxiety that younger participants may experience with certain clinical assessments including MRI, biopsies, and blood draws

 • Required a clear rationale for the need for biopsies, provided advice on how best to educate on the reasons for such a procedure, and were supportive of providing detailed information to trial participants

 • Were supportive of endpoints related to activities of daily living as illustrative and useful in assessing the impact of an investigational therapeutic

The CAB:

 • Supported proposed plans to minimize the number of placebo participants as much as possible, recognizing that the decision depends on several factors

 • Endorsed the approaches to define a sequential order of assessments for all outcome measures for consistency and intentions for modifying endpoint and outcome measures

Clinical trial protocol elements (DM1 advisory workshop specific feedback)

Advisory participants helped dyne:

 • Identify the multiple factors (e.g., temperature, activity, sleep) that impact accurate quantification of myotonia

 • Identify specific opportunities for education regarding assessments that could be considered more challenging (e.g., where recovery and healing many be needed)

 • Consider the factors such as travel and time of day that influence disease manifestations (including fatigue level, strength, GI symptoms, and overall performance) in order to optimize the design and interpretation of test results

 • Better understand the challenges of performing functional assessments in the clinic

Advisory participants:

 • Considered pulmonary testing important

 • Considered muscle needle biopsies important to provide accurate assessment of potential therapeutics

Study visits (DMD and DM advisory workshop participants and duchenne CAB feedback)

Advisory participants recommended that Dyne:

 • Provide a detailed itinerary and schedule to ensure a smooth clinic visit

 • Build flexibility in the timing of assessments to help with individual participant needs

 • Minimize travel burden through financial and organizational support (critically important): have travel and patient support programs that provide fit-for-purpose, long-distance and cross-border travel, meals, housing, insurance, and related support programs

 • Provide age-appropriate communication to engage participants

 • Communicate trial status information through research coordinators