FRAGMENT ANTIBODY TARGETING HUMAN TFR1 CONJUGATED TO PHOSPHORODIAMIDATE MORPHOLINO OLIGOMER for Duchenne muscular dystrophy

Inclusion criteria

• {"criterion_text":"- Age 4 to 16 years inclusive, at the time of informed consent/assent."}
• {"criterion_text":"- Male with a confirmed diagnosis of DMD and with a mutation in the dystrophin gene characterized by exon deletion amenable to exon 51 skipping."}
• {"criterion_text":"- Upper extremity muscle group that is amenable to muscle biopsy."}
• {"criterion_text":"- Brooke Upper Extremity Scale score of 1 or 2."}
• {"criterion_text":"- Ambulatory or non-ambulatory. A non-ambulatory participant must have been non-ambulatory for <2 years before enrolment."}
• {"criterion_text":"- Receiving a stable dosage of glucocorticoids for at least 12 weeks prior to the start of study drug administration."}
• {"criterion_text":"- Left ventricular ejection fraction of ≥50% by echocardiogram or ≥ 55% by cardiac magnetic resonance imaging (MRI)."}

Exclusion criteria

• {"criterion_text":"- Uncontrolled clinical symptoms and signs of congestive heart failure (CHF)."}
• {"criterion_text":"- Any change in prophylaxis/treatment for CHF within 3 months prior to the start of study treatment."}
• {"criterion_text":"- History of major surgical procedure within 12 weeks prior to the start of study drug administration or an expectation of a major surgical procedure during the study."}
• {"criterion_text":"- Requirement of daytime ventilator assistance."}
• {"criterion_text":"- Percent predicted FVC <40 % (applies only for participants who are age ≥7 years)."}
• {"criterion_text":"- Receipt of eteplirsen, or alternative exon-skipping/dystrophinmodifying therapy, within 12 weeks of randomization."}
• {"criterion_text":"- Receipt of non-exon skipping investigational drug within 4 months before the start of study drug administration."}
• {"criterion_text":"- Receipt of gene therapy at any time."}

Primary endpoints

• {"endpoint_text":"- Number and proportion of participants with treatment-emergent adverse events (TEAEs), treatment emergent serious adverse events (TESAEs), TEAEs considered related to study drug, and TEAEs leading to discontinuation from study drug and discontinuation from the study.","definition_or_measurement_approach":"Counts and proportions of participants experiencing TEAEs, TESAEs, drug-related TEAEs, and TEAEs leading to discontinuation."}
• {"endpoint_text":"- Change from Baseline in dystrophin protein levels in muscle tissue as determined by Western blot analysis at Week 25","definition_or_measurement_approach":"Change from baseline measured by Western blot analysis of dystrophin protein levels in muscle tissue at Week 25."}

Secondary endpoints

• {"endpoint_text":"- Muscle Tissue Endpoints: Cohorts dosed Q4W or Q8W with a second biopsy at Week 25","definition_or_measurement_approach":"Muscle tissue assessments with second biopsy at Week 25 for cohorts dosed Q4W or Q8W."}
• {"endpoint_text":"- Change from Baseline at Week 25: -exon 51 skipping levels in muscle tissue -PDPF in muscle tissue -PMO concentration in muscle tissue","definition_or_measurement_approach":"Change from baseline at Week 25 in exon 51 skipping levels, percent dystrophin-positive fibers (PDPF), and PMO concentration in muscle tissue."}
• {"endpoint_text":"- Change from baseline up to Week 145: -blood CK levels","definition_or_measurement_approach":"Change from baseline in blood creatine kinase (CK) levels measured up to Week 145."}
• {"endpoint_text":"- Cohorts dosed Q8W with a second biopsy at Week 49 Change from Baseline at Week 49 in: -dystrophin protein levels in muscle tissue -exon 51 skipping levels in muscle tissue -PDPF in muscle tissue -PMO concentration in muscle tissue","definition_or_measurement_approach":"For Q8W cohorts, second biopsy at Week 49 with change from baseline in dystrophin, exon 51 skipping, PDPF, and PMO concentration in muscle tissue."}
• {"endpoint_text":"- Change from Baseline up to Week 145 in: -blood CK level","definition_or_measurement_approach":"Change from baseline in blood CK levels assessed up to Week 145."}
• {"endpoint_text":"- Functional Endpoints: All cohorts","definition_or_measurement_approach":"Functional assessments across all cohorts (details in protocol questionnaires)."}
• {"endpoint_text":"- Change from Baseline up to Week 145 in: -PUL scale V 2.0 score -%pFVC -NSAA total score, TTR, 10MRW, and SV95C in ambulatory participants","definition_or_measurement_approach":"Change from baseline up to Week 145 in PUL v2.0, percent predicted FVC, NSAA total score, time-to-rise (TTR), 10-meter run/walk (10MRW), and stride velocity 95th centile (SV95C) in ambulatory participants."}
• {"endpoint_text":"- Plasma Endpoints: All cohorts -Cmax -tmax -AUCtlast -AUC∞ -λZ -t½ -CL -Vz and Vss, if appropriate","definition_or_measurement_approach":"Plasma pharmacokinetic parameters (Cmax, Tmax, AUCtlast, AUC∞, λZ, t½, CL, Vz, Vss) as appropriate."}
• {"endpoint_text":"- Immunogenicity Endpoint: All cohorts -Incidence of ADAs","definition_or_measurement_approach":"Incidence of anti-drug antibodies (ADAs) across all cohorts."}

Methods

• Recruitment via participating hospital/clinic paediatric neurology departments at listed trial sites (country-specific site lists for Belgium, Italy, Spain, Ireland).
• Country-specific recruitment arrangements documents (K1 files) prepared for Belgium, Italy, Spain, and Ireland (e.g. 'K1_DYNE251-DMD-201_Recruitment-Arrangments_ES_Public' and equivalents).
• GP letters for recruitment in Italy (document 'K2_DYNE251-DMD-201_GP Letter_IT_Public').
• Use of patient recruitment materials produced by contracted third parties (Matthews Media Group Inc. listed with duty 'Patient recruitment material').
• Use of travel reimbursement and relocation support to facilitate participation (documents and third parties listed for travel reimbursement and patient travel services).

Belgium

Earliest CTIS Part Ii Submission Date

24-06-2024

Latest Decision Or Authorization Date

16-07-2024

Processing Time Days

22

Number Of Sites

3

Number Of Participants

5

Italy

Earliest CTIS Part Ii Submission Date

21-06-2024

Latest Decision Or Authorization Date

16-07-2024

Processing Time Days

25

Number Of Sites

4

Number Of Participants

3

Spain

Earliest CTIS Part Ii Submission Date

24-06-2024

Latest Decision Or Authorization Date

09-07-2024

Processing Time Days

15

Number Of Sites

2

Number Of Participants

7

Ireland

Earliest CTIS Part Ii Submission Date

24-06-2024

Latest Decision Or Authorization Date

09-07-2024

Processing Time Days

15

Number Of Sites

1

Number Of Participants

1

Primary sponsor

Full Name

Dyne Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

PPD Development LP

Name

Pharmaceutical Product Development LLC

Responsibilities

Safety Management, Medical monitoring

Name

PPD Global Central Labs

Responsibilities

Clinical Chemistry, Clinical haematology

Third parties

• {"country":"United Kingdom","full_name":"ATOM International Limited","duties_or_roles":"Functional Assessment QC (Inter-site reliability and quality)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Canada","full_name":"AGADA Biosciences Inc.","duties_or_roles":"Muscle Biopsy Sample Management","organisation_type":"Health care"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Perkinelmer Genetics Inc.","duties_or_roles":"DMD Genomics Assay","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"Clinical Chemistry, Clinical haematology","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Flagship Biosciences Inc.","duties_or_roles":"Histopathology","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Casimir LLC","duties_or_roles":"Duchenne Video Assessment","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pharma Start LLC","duties_or_roles":"Home nursing service provider","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Central reading for ECG (cardiac safety)","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Charles River Laboratories Montreal ULC","duties_or_roles":"Immunogenecity/ADA assay","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Matthews Media Group Inc.","duties_or_roles":"Patient recruitment material","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Chillibean Limited","duties_or_roles":"Clinical Trial Video Services: Video file storage, Functional assessment videos","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"Safety Management, Medical monitoring","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Sysnav","duties_or_roles":"providing a patient wearable device to collect stride velocity 95th centile (SV95C) data","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical image analysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Myriad RBM Inc.","duties_or_roles":"Clinical chemistry","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"Muscle DMPK and Splicing","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Arup Laboratories Inc.","duties_or_roles":"Clinical chemistry","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient travel and patient reimbursement services","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"Patient Reported Outcome licensing, validation, translation","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"IVRS – treatment randomisation","organisation_type":"Pharmaceutical company"}