Effects of BBP-418 (ribitol) in Patients with LGMD2I

Overview

Sponsor-declared trial summary

Key facts

Sponsor

ML Bio Solutions Inc.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

12 Feb 2024 → ongoing

Decision date (initial)

2024-01-29

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

ML Bio Solutions, Inc.

External identifiers

EU CT number

2023-503379-33-01

WHO UTN

U1111-1287-7720

ClinicalTrials.gov

NCT05775848

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

To assess the clinical efficacy and safety of BBP-418 in patients with LGMD2I/ R9

Secondary objectives 2

1. To assess the clinical efficacy of BBP-418 in patients with LGMD2I/ R9
2. To assess biomarkers for clinical efficacy of BBP-418 in patients with LGMD2I/ R9

Conditions and MedDRA coding

Limb Girdle Muscular Dystrophy 2I/R9

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-002887-PIP01-20

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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 18 to 60 years of age (inclusive).
3. Have a body weight >30 kg.
4. The participant who signs the informed consent form (ICF) understands the study procedures and the participant agrees to participate in the study by giving informed consent.
5. Women of childbearing potential (WOCBP) 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.

Exclusion criteria 10

1. Evidence of clinically significant concomitant disease, including: Any significant concomitant medical condition, including cardiac, renal, pulmonary, hepatic, or endocrine disease other than that associated with LGMD2I/ R9; Moderate to severe renal impairment (eGFR < 60 mL/min/1.73 m2 based on cystatin C[CysC], as calculated by central laboratory; 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; 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. 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).
3. Presence of a platelet disorder, bleeding disorder, or other contraindication to muscle biopsy.
4. Actively on an experimental therapy or device, was on an experimental therapy or device within 90 days prior to the Screening Visit, or was on BBP-418 at any time
5. 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.
6. 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 enrol in this study provided all inclusion and no other exclusion criteria are met.)
7. 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.
8. Use of ribose or other sugar alcohol-containing supplement within 90 days of the Screening Visit.
9. 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.)
10. Previously received gene therapy to treat LGMD2I/ R9.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Change from baseline in NSAD at 36 months
2. Frequency and severity of TEAEs and TESAEs
3. Results of physical examinations including vital signs
4. Chemistry and hematology laboratory analyses
5. 12-lead ECG, including QTc intervals

Secondary endpoints 7

1. Change from baseline in 10MWT (velocity, m/s) at 36 months
2. Change from baseline in pulmonary function as measured by FVC (percent predicted, performed in a sitting position) at 36 months
3. Change from baseline in the PUL2.0 at 36 months
4. Change from baseline in NSAD at 36 months
5. Change from baseline in total glycosylated αDG expression
6. Change from baseline in glycosylated αDG/ total αDG ratio
7. Change from baseline in pre-functional assessment serum CK

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

ML Bio Solutions Inc.

Sponsor organisation

ML Bio Solutions Inc.

Address

1800 Owens Street Suite C1200

City

San Francisco

Postcode

94158-2584

Country

United States

Scientific contact point

Organisation

ML Bio Solutions Inc.

Contact name

Chief Medical Officer

Public contact point

Organisation

ML Bio Solutions Inc.

Contact name

Director, Clinical Operations

Third parties 2

Locations

5 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 46 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

15 submissions — initial application plus substantial / non-substantial modifications