Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05775848




Registration number
NCT05775848
Ethics application status
Date submitted
16/02/2023
Date registered
20/03/2023
Date last updated
7/06/2024

Titles & IDs
Public title
Study to Evaluate the Efficacy and Safety of BBP-418 (Ribitol) in Patients With Limb Girdle Muscular Dystrophy 2I (LGMD2I)
Scientific title
A Phase 3 Randomized, Placebo-controlled, Double-blind Study to Evaluate the Efficacy and Safety of BBP-418 (Ribitol) in Patients With Limb Girdle Muscular Dystrophy 2I (LGMD2I)
Secondary ID [1] 0 0
MLB-01-005
Universal Trial Number (UTN)
Trial acronym
Fortify
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Limb-Girdle Muscular Dystrophy Type 2I (LGMD2I) 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BBP-418 (ribitol)
Other interventions - Placebo

Active Comparator: BBP-418 - BBP-418 Granules for Oral Solution will be supplied as granules in tri-ply PET/Aluminum/PE sachets for unit dose. The number of sachets to reconstitute will depend on the applicable dose to be delivered, 9 g BID or 12 g BID, as determined by the weight of the participant. The granules will be reconstituted in water for oral administration.

Placebo Comparator: Placebo to Match BBP-418 - The placebo will be identical to the BBP-418 Granules for Oral Solution in appearance, packaging, labeling, and storage conditions.


Treatment: Drugs: BBP-418 (ribitol)
The BBP-418 drug product is provided as Granules for Oral solution consisting of BBP-418 drug substance and silicon dioxide in a multilaminate sachet with a foil barrier. Silicon dioxide is generally regarded as safe and listed in the FDA IIAD. Silicon dioxide is a compendial excipient and is commonly used in pharmaceutical dosage forms. The BBP-418 Granules for Oral Solution are provided in sachets to provide 3 g BBP-418 per sachet. The BBP-418 Granules for Oral Solution are reconstituted in water for oral administration.

Other interventions: Placebo
A placebo matched for similar taste and appearance was compounded at the clinical pharmacy with sucralose as a 0.35 mg/mL oral solution in purified water (USP) in a glass container. Sucralose is similar in taste to the compounded drug product.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from baseline in North Star Assessment for Limb Girdle Muscular Dystrophy following 36 months of treatment to assess efficacy of BBP-418 or placebo
Timepoint [1] 0 0
36 months
Primary outcome [2] 0 0
Frequency and severity of treatment-emergent adverse events following 36 months of treatment to assess safety of BBP-418 or placebo
Timepoint [2] 0 0
36 months
Secondary outcome [1] 0 0
Change from baseline in 10 meter walk test velocity to assess the clinical efficacy of BBP-418 in patients with LGMD2I/R9
Timepoint [1] 0 0
36 months
Secondary outcome [2] 0 0
Change from baseline in pulmonary function as measured by FVC (percent predicted, performed in a sitting position) to assess the clinical efficacy of BBP-418 in patients with LGMD2I/R9
Timepoint [2] 0 0
36 months
Secondary outcome [3] 0 0
Change from baseline in the Performance of Upper Limb scale 2.0 to assess the clinical efficacy of BBP-418 in patients with LGMD2I/R9
Timepoint [3] 0 0
36 months

Eligibility
Key inclusion criteria
Participants must meet all the following criteria to be enrolled:

1. Have a genetically confirmed diagnosis of LGMD2I/R9 (including review of records of
previous molecular genetic testing) and be clinically affected (defined as
demonstrating clinical weakness on bedside evaluation in either a limb-girdle pattern,
or in a distal extremity).

2. Male or female participants 12 to 60 years of age (inclusive).

3. Have a body weight >30 kg.

4. The participant (or parent/guardian) who signs the ICF understands the study
procedures and the participant agrees to participate in the study by giving informed
consent (and assent, if <18 years of age).

5. Female participants of childbearing potential and male participants of reproductive
potential must be willing to use a highly effective method of contraception from time
of consent through 12 weeks after last dose.

6. Willing and able to complete all study procedures, including biopsies, according to
the Schedule of Assessments (see Appendix 1).

Participants must not meet any of the following criteria to be enrolled:

1. Evidence of clinically significant concomitant disease, including:

1. Any significant concomitant medical condition, including mental, cardiac, renal,
pulmonary, hepatic, or endocrine disease other than that associated with
LGMD2I/R9.

2. Moderate to severe renal impairment (estimated glomerular filtration rate [eGFR]
of < 60 mL/min/1.73 m2 based on cystatin C [CysC]), as calculated by the central
laboratory.

3. Any other laboratory, vital sign, ECG abnormality, clinical history, or finding
that, in the Investigator's opinion, is likely to unfavorably alter the
risk-benefit of study participation, confound study results, or interfere with
study conduct or compliance.

4. Surgery for scoliosis or other indication that will significantly impact the
participant's ability to execute clinical assessments planned or expected to be
required to manage curvature within 12 months following the Screening Visit.

2. A participant with a score of zero on any one or more of the primary or key secondary
endpoints at the time of screening. (Participants who previously completed
participation in Study MLB-01-001 and would be excluded due to this criterion may
enroll in this study provided all inclusion and no other exclusion criteria are met.)

3. If pregnant and/or breastfeeding or planning to conceive children within the projected
duration of the study through 12 weeks after the last dose of study treatment.

4. Use of ribose or other sugar alcohol-containing supplement within 90 days of the
Screening Visit.

5. Use of a systemic corticosteroid for the treatment of muscular dystrophy within 90
days of the Screening Visit. (An inhaled corticosteroid or bronchodilator for reactive
airway disease is allowed if the participant is on a stable dose for 30 days prior to
study entry.)

6. Previously received gene therapy to treat LGMD2I/R9.

7. Participants with active suicidal ideation as measured by Columbia-Suicide Severity
Rating Scale during screening with most severe suicide ideation score of 4 (Active
Suicidal Ideation with Some Intent to Act, without Specific Plan) or 5 (Active
Suicidal Ideation with Specific Plan and Intent).

8. Presence of a platelet disorder, bleeding disorder, or other contraindication to
muscle biopsy.

9. Actively on an experimental therapy or device or was on an experimental therapy or
device within 90 days of the Screening Visit.

10. In the judgment of the Investigator or Medical Monitor, has any clinically important
ongoing medical condition or laboratory abnormality or condition that might jeopardize
the participant's safety, increase their risk from participation, or interfere with
the study. For COVID-19 infections, Investigator should refer to local guidance.
Minimum age
12 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/05/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2027
Actual
Sample size
Target
81
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Royal Brisbane and Women's Hospital, - Brisbane
Recruitment postcode(s) [1] 0 0
- Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Iowa
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
Denmark
State/province [15] 0 0
Copenhagen
Country [16] 0 0
Italy
State/province [16] 0 0
Milan
Country [17] 0 0
Netherlands
State/province [17] 0 0
Leiden
Country [18] 0 0
Norway
State/province [18] 0 0
Tromsø
Country [19] 0 0
United Kingdom
State/province [19] 0 0
London
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Newcastle Upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ML Bio Solutions, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate the safety and efficacy of long-term administration of BBP-418 in
patients with LGMD2I/R9. The study will include patients ages 12 to 60, consistent with the
existing preclinical toxicology profile. This will encompass the significant majority of
existing diagnosed patients based upon the established epidemiology of the disease.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05775848
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
ML Bio Soultions Patient Information
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
info@mlbiosolutions.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05775848