Frequently Asked Questions

LEAD-IN STUDY (also referred to as the Natural History Study)

ML Bio Solutions, Inc (ML Bio) has begun a non-interventional study for LGMD2I (LGMD R9-FRKP related), enrolling patients at sites across the United States and in Europe. The primary goal of the lead-in study is to understand how LGMD2I affects people with the disease over time. By measuring biomarkers (biological measures that assess health and disease such as blood tests, MRI and muscle biopsy), mobility, strength and other factors we can then determine which assessments would be most appropriate endpoints for future clinical trials of BBP-418 (Ribitol).

This is an observational study and does not involve study drug. Instead, the study is an opportunity for researchers to understand the course of the disease by evaluating the most meaningful and sensitive outcome measures.

The lead-in study will precede the clinical trials involving BBP-418, called an interventional clinical trial. Participants in the lead-in study will have an opportunity to participate in the interventional clinical trials (as long as it is safe to do so).

Please see the illustrations on the ML Bio website that explain the drug development process and the status of the BBP-418 studies in the context of that process.

LGMD2I natural history studies and LGMD disease registries provide valuable information that contribute to our understanding of the disease.

Where the ML Bio sponsored lead-in study differs is that it also is designed to collect outcome and biomarker information at up to 6 months intervals, that can help to accelerate roll-out of an interventional trial that is designed to be as efficient (e.g., as short) as possible. The ML Bio lead-in study will assess the potential of muscle tissue biopsy and MRI, as well as more routine functional outcome measures, to demonstrate measurable changes over time. The lead-in study will precede the interventional clinical trials involving BBP-418. The lead-in study will precede the clinical trials involving BBP-418, called an interventional clinical trial. Participants in the lead-in study will have an opportunity to participate in the interventional clinical trials (as long as it is safe to do so).

Ongoing natural history studies, including the ML Bio sponsored lead-in study, and disease registry datasets are designed to collect similar information from patients, such as age at diagnosis, current age, gender, genotype, etc. The ML Bio lead-in study is additionally collecting molecular and functional outcome data that is not being collected by other natural history studies and registries. Without this information, it is unlikely that such an interventional trial could be designed to meet the standards of the FDA or other regulatory agencies.

You must be at least 10 years old but not older than 65 years old at the time you enroll in the study (18-65 in Denmark) and have genetic confirmation of a mutation in the gene FKRP (LGMD-2I). A predefined number of patients with different levels of ambulatory ability, including a certain number of non-ambulatory patients, will be enrolled to ensure that the lead-in patient panel represent both moderate and more advanced stages of LGMD2I disease.

Patients enrolled in the lead-in study will undergo baseline evaluation for several clinical measures and imaging or laboratory measures of the disease course in LGMD2I:

  • Muscle biopsy obtained using a needle (fine needle aspiration biopsy)
  • Muscle MRI of the legs will measure the amount of scarring (“fibrosis”) and fat
  • Potential clinical trial endpoints such as: 10-meter walk test, 100-meter walk test, 4- stair climb test, timed up and go test, and the Modified North Star Assessment for Limb Girdle Muscular Dystrophy
  • Pulmonary (lung) function
  • Assessment of quality of life and activities of daily living using patient reported outcomes

For these clinical measures and potential biomarkers, it is important to measure repeatedly at 0, 6 and 12-month timepoints in order to establish firstly that they can be measured in a consistent and standardized way, and secondly to determine how stable these measures are over time. Both the reproducibility of the measurement and its change over time in an observational (non-interventional) study can help determine if they can robustly be used to show the same in an interventional trial.

ML Bio uses a variety of patient-reported outcomes to measure day-to-day activities.

There is a total of 5 visits for this study. The Baseline assessments are collected over 2 consecutive days. The third visit is a one-day visit 6 months after you enroll in the study and then there are 2 additional one-day visits every 3 months with the last visit at month 12.

The COVID-19 associated restrictions on patient travel to sites for research study visits, as well as on-site research staffing, have together delayed enrollment in the lead-in study and also prompted the consideration of remote (not in-person) assessments for active sites.

With respect to enrollment, the study sites nevertheless have been working to be ready to enroll when restrictions are lifted on a site by site basis. On the ML Bio website there is a map of study sites, which are color-coded to show activation status (yellow for pending activation; green for active).

With respect to challenges on travel to active sites, ML Bio is developing a protocol addendum that may permit enrollment and monitoring of selected clinical endpoints to be performed remotely (on a site by site basis).

Your participation in this study will help the ML Bio and other researchers learn more about Limb Girdle Muscular Dystrophy and facilitate the drug development process.

There are no direct benefits you can expect to receive as a result of participating in the ML Bio lead-in study. The lead-in study will precede the clinical trials involving BBP-418, called an interventional clinical trial. Participants in the lead-in study will have an opportunity to participate in the interventional clinical trials (as long as it is safe to do so).

The cost of travel as well as a personal stipend will be covered by ML Bio.

SUBSEQUENT CLINICAL TRIAL AND ACCESS TO TREATMENT

Participation in any clinical trial is voluntary. Participants in the lead-in study will be invited to participate in the interventional clinical trials (as long as it is safe to do so).

The exact structure of our interventional clinical trials has not yet been determined. Details (study protocol, inclusion and exclusion criteria, etc.) will be subjected to guidance and approval by the FDA and other regulatory agencies. This information will be made available as it is finalized.

Your child can participate in a clinical trial if they meet enrollment requirements that ML Bio has included in the clinical trial protocol. You and your child will need to consent to trial participation. (You may need to provide consent for your child depending on his/her age.) The FDA has guidelines to support trials that involve children and ML Bio will need to comply with these guidelines.

As d-ribose is a similar chemical formulation as Ribitol, use of this over-the-counter supplement could confound the results. Therefore, a “washout” period, during which a study participant stops taking d-ribose, will be required before being able to enroll.