Clinical trial • Phase III • Musculoskeletal
TALDEFGROBEP ALFA for Spinal muscular atrophy
Phase III trial of TALDEFGROBEP ALFA for Spinal muscular atrophy.
Overview
- Trial Therapeutic Area
- Musculoskeletal
- Trial Disease
- Spinal muscular atrophy
- Trial Stage
- Phase III
- Drug Modality
- Peptide/protein/enzyme
- Paediatric Trial
- Yes
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 17-06-2024
- First CTIS Authorization Date
- 09-07-2024
Trial design
Randomised, placebo solution for injection in pre-filled syringe (placebo arm).-controlled Phase III trial across 21 sites in Belgium, Spain, Poland and others.
- Randomised
- Yes
- Comparator
- Placebo Solution for injection in pre-filled syringe (placebo arm).
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 76
- Trial Duration For Participant
- 336
Eligibility
Recruits 76 paediatric patients.
- Vulnerable Population
- The trial includes vulnerable populations (paediatric participants/minors). Multiple age-appropriate subject information sheets, consent and assent forms are provided (examples include ICFs and assent forms for ages 4-11, 6-11, 7-12, 8-11, 12-16/12-17 and versions for Parents/Legal Guardians). Genetic testing assent documents are provided. Consent is obtained from adults and from parents/legal guardians for minors, with assent forms for children/adolescents as appropriate; documents are available in multiple languages (examples in the dossier: Dutch, English, French, Spanish, Polish, Italian, German, Czech).
Inclusion criteria
- {"criterion_text":"- Spinal Muscular Atrophy confirmed by genetic diagnosis of 5q-autosomal recessive SMA as well as SMN2 copy number\n- Ambulant or Non-ambulant\n- Treated with an SMA disease-modifying therapy and anticipated to remain on that same treatment regimen dose throughout the trial including nusinersen, risdiplam and/or history of onasemnogene abeparvovec"}
Exclusion criteria
- {"criterion_text":"- Cannot have previously taken anti-myostatin therapies\n- Must weigh at least 15 kg\n- Respiratory insufficiency, defined by the medical necessity for invasive or non-invasive ventilation for daytime treatment while awake (use overnight or during daytime naps is acceptable).\n- History of Spinal Fusion within 6 months of Screening. MAGEC rod non-surgical adjustments are allowed during the study\n- Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system (CNS) catheter"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Change from baseline in the MFM-32 at Week 48","definition_or_measurement_approach":"Change in the 32-item Motor Function Measure (MFM-32) total score between Baseline and Week 48."}
Secondary endpoints
- {"endpoint_text":"- Change from baseline in the RULM at Week 48","definition_or_measurement_approach":"Change from baseline in the Revised Upper Limb Module (RULM) total score at Week 48."}
- {"endpoint_text":"- Change from baseline in the RHS at Week 48","definition_or_measurement_approach":"Change from baseline in the Revised Hammersmith Scale (RHS) total score at Week 48."}
- {"endpoint_text":"- Safety and tolerability assessments including change in lean body mass and bone mineral density on DXA scan from baseline at Week 48 and Tanner staging for puberty monitoring, monitoring of injection acceptability assessments, and frequency of unique subjects with: new or worsening lab abnormalities, treatment related adverse events, serious adverse events, and adverse events leading to discontinuation.","definition_or_measurement_approach":"Safety and tolerability assessed by change from baseline in lean body mass and bone mineral density (DXA) at Week 48, Tanner staging, injection acceptability assessments, and counts/frequency of lab abnormalities, treatment-related AEs, serious AEs and AEs leading to discontinuation."}
- {"endpoint_text":"- Trough plasma concentrations of taldefgrobep alfa and pharmacokinetic parameters estimated with population PK modeling","definition_or_measurement_approach":"Measurement of trough plasma concentrations and estimation of PK parameters using population pharmacokinetic (PK) modeling."}
Recruitment
- Digital Remote Recruitment
- Yes
- Planned Sample Size
- 76
- Recruitment Window Months
- 32
- Consent Approach
- Informed consent obtained from adult participants; for minors consent is obtained from parents/legal guardians with age-appropriate assent forms for children/adolescents (multiple ICF and assent templates are included for age bands such as 4-11, 6-11, 7-12, 8-11, 12-16/12-17 and 13-AOM). Genetic-testing-specific assent/consent documents are provided. Documents are available in multiple languages across Member States (examples include Dutch, English, French, Spanish, Polish, Italian, German, Czech).
Methods
- Science37 Platform (decentralised/remote platform) — materials and platform start-up guides are listed in documents
- Sponsor/Study Website materials (BHV2000-301_WEBSITE_Study Medication / Activities / Participate / RESILIENT) — web channel
- Email communications to potential participants (L2_Other subject information material_Email Comm)
- Direct mail/postcards (Postcard for patients)
- Scout/Specialist patient engagement (Scout ICF, Scout Study Brochure, Patient Concierge Services) and ScoutPass Mailer/Reloadable Brochures
- GP-to-specialist / specialist letters (GP-Specialist Letter)
- Patient study brochures, explainer video and multimedia (Explainer video transcript, Live Stream Video)
- Local site recruitment via participating hospitals/neuromuscular centres (country site lists in Part II)
Geography
- Total Number Of Sites
- 21
- Total Number Of Participants
- 104
Belgium
- Earliest CTIS Part Ii Submission Date
- 05-07-2024
- Latest Decision Or Authorization Date
- 16-07-2024
- Processing Time Days
- 11
- Number Of Sites
- 3
- Number Of Participants
- 11
Sites
- Site Name
- Antwerp University Hospital
- Principal Investigator Name
- Diane Beysen
- Principal Investigator Email
- diane.beysen@uza.be
- Contact Person Name
- Diane Beysen
- Contact Person Email
- diane.beysen@uza.be
- Site Name
- Universiteit Gent
- Principal Investigator Name
- Nicolas Deconinck
- Principal Investigator Email
- nicolas.deconinck@huderf.be
- Contact Person Name
- Nicolas Deconinck
- Contact Person Email
- nicolas.deconinck@huderf.be
- Site Name
- UZ Leuven
- Principal Investigator Name
- Liesbeth De Waele
- Principal Investigator Email
- liesbeth.dewaele@uzleuven.be
- Contact Person Name
- Liesbeth De Waele
- Contact Person Email
- liesbeth.dewaele@uzleuven.be
Spain
- Earliest CTIS Part Ii Submission Date
- 05-07-2024
- Latest Decision Or Authorization Date
- 16-07-2024
- Processing Time Days
- 11
- Number Of Sites
- 4
- Number Of Participants
- 25
Sites
- Site Name
- Hospital Universitario Donostia
- Principal Investigator Name
- Roberto Fernandez Torron
- Principal Investigator Email
- roberto.fernandeztorron@osakidetza.eus
- Contact Person Name
- Roberto Fernandez Torron
- Contact Person Email
- roberto.fernandeztorron@osakidetza.eus
- Site Name
- Hospital Universitario Y Politecnico La Fe
- Principal Investigator Name
- Inmaculada Pitarch Castellano
- Principal Investigator Email
- neuromuscularpediatrico_lafe@gva.es
- Contact Person Name
- Inmaculada Pitarch Castellano
- Contact Person Email
- neuromuscularpediatrico_lafe@gva.es
- Site Name
- Hospital Sant Joan De Deu Barcelona
- Principal Investigator Name
- Andres Nascimento
- Principal Investigator Email
- andres.nascimento@sjd.es
- Contact Person Name
- Andres Nascimento
- Contact Person Email
- andres.nascimento@sjd.es
- Site Name
- Hospital Universitario Regional De Malaga
- Department Name
- Department of Pediatric Neurology
- Principal Investigator Name
- Rocio Calvo Medina
- Principal Investigator Email
- rrro@hotmail.com
- Contact Person Name
- Rocio Calvo Medina
- Contact Person Email
- rrro@hotmail.com
Poland
- Earliest CTIS Part Ii Submission Date
- 05-07-2024
- Latest Decision Or Authorization Date
- 06-08-2024
- Processing Time Days
- 32
- Number Of Sites
- 4
- Number Of Participants
- 22
Sites
- Site Name
- Uniwersytecki Szpital Kliniczny W Poznaniu
- Principal Investigator Name
- Barbara Steinborn
- Principal Investigator Email
- bstein@ump.edu.pl
- Contact Person Name
- Barbara Steinborn
- Contact Person Email
- bstein@ump.edu.pl
- Site Name
- Dolnoslaski Szpital Specjalistyczny Im. T.Marciniaka-Centrum Medycyny Ratunkowej
- Department Name
- Department of Pediatric Neurology
- Principal Investigator Name
- Barbara Ujma-Czapska
- Principal Investigator Email
- ujma_czapska@gazeta.pl
- Contact Person Name
- Barbara Ujma-Czapska
- Contact Person Email
- ujma_czapska@gazeta.pl
- Site Name
- Instytut Pomnik Centrum Zdrowia Dziecka
- Department Name
- Department of Neurology and Epileptology
- Principal Investigator Name
- Katarzyna Kotulsta-Jozwiak
- Principal Investigator Email
- k.kotulska@ipczd.pl
- Contact Person Name
- Katarzyna Kotulsta-Jozwiak
- Contact Person Email
- k.kotulska@ipczd.pl
- Site Name
- Uniwersyteckie Centrum Kliniczne
- Department Name
- Department of Developmental Neurology
- Principal Investigator Name
- Maria Mazurkiewicz-Beldzinska
- Principal Investigator Email
- maria.mazurkiewicz-beldzinska@gumed.edu.pl
- Contact Person Name
- Maria Mazurkiewicz-Beldzinska
- Contact Person Email
- maria.mazurkiewicz-beldzinska@gumed.edu.pl
Netherlands
- Earliest CTIS Part Ii Submission Date
- 05-07-2024
- Latest Decision Or Authorization Date
- 09-07-2024
- Processing Time Days
- 4
- Number Of Sites
- 1
- Number Of Participants
- 8
Sites
- Site Name
- Universitair Medisch Centrum Utrecht
- Principal Investigator Name
- Ludo Van der Pol
- Principal Investigator Email
- w.l.vanderpol@umcutrecht.nl
- Contact Person Name
- Ludo Van der Pol
- Contact Person Email
- w.l.vanderpol@umcutrecht.nl
Germany
- Earliest CTIS Part Ii Submission Date
- 05-07-2024
- Latest Decision Or Authorization Date
- 11-07-2024
- Processing Time Days
- 6
- Number Of Sites
- 3
- Number Of Participants
- 16
Sites
- Site Name
- Universitaetsklinikum Essen AöR
- Department Name
- Department of Pediatrics
- Principal Investigator Name
- Andrea Gangfuss
- Principal Investigator Email
- andrea.gangfuss@uk-essen.de
- Contact Person Name
- Andrea Gangfuss
- Contact Person Email
- andrea.gangfuss@uk-essen.de
- Site Name
- Medical Center - University Of Freiburg
- Department Name
- Department of Neuropediatrics
- Principal Investigator Name
- Astrid Pechmann
- Principal Investigator Email
- astrid.pechmann@uniklinik-freiburg.de
- Contact Person Name
- Astrid Pechmann
- Contact Person Email
- astrid.pechmann@uniklinik-freiburg.de
- Site Name
- Klinikum der Universitaet Muenchen AöR
- Principal Investigator Name
- Astrid Blaschek
- Principal Investigator Email
- astrid.blaschek@med.uni-muenchen.de
- Contact Person Name
- Astrid Blaschek
- Contact Person Email
- astrid.blaschek@med.uni-muenchen.de
Italy
- Earliest CTIS Part Ii Submission Date
- 05-07-2024
- Latest Decision Or Authorization Date
- 12-08-2024
- Processing Time Days
- 38
- Number Of Sites
- 4
- Number Of Participants
- 11
Sites
- Site Name
- Azienda Unita Sanitaria Locale Di Bologna
- Principal Investigator Name
- Antonella Pini
- Principal Investigator Email
- antonella.pini@isnb.it
- Contact Person Name
- Antonella Pini
- Contact Person Email
- antonella.pini@isnb.it
- Site Name
- Fondazione Istituto Neurologico Nazionale Casimiro Mondino
- Principal Investigator Name
- Angela Lucia Berardinelli
- Principal Investigator Email
- angela.berardinelli@mondino.it
- Contact Person Name
- Angela Lucia Berardinelli
- Contact Person Email
- angela.berardinelli@mondino.it
- Site Name
- Ospedale Pediatrico Bambino Gesu
- Department Name
- Department of Neuroscience
- Principal Investigator Name
- Adele D'Amico
- Principal Investigator Email
- adele2.damico@opbg.net
- Contact Person Name
- Adele D'Amico
- Contact Person Email
- adele2.damico@opbg.net
- Site Name
- Centro Clinico Nemo
- Principal Investigator Name
- Massimiliano Filosto
- Principal Investigator Email
- massimiliano.filosto@unibs.it
- Contact Person Name
- Massimiliano Filosto
- Contact Person Email
- massimiliano.filosto@unibs.it
Czechia
- Earliest CTIS Part Ii Submission Date
- 05-07-2024
- Latest Decision Or Authorization Date
- 28-08-2024
- Processing Time Days
- 54
- Number Of Sites
- 2
- Number Of Participants
- 11
Sites
- Site Name
- Fakultni Nemocnice Brno
- Department Name
- Department of Pediatric Neurology
- Principal Investigator Name
- Lenka Jurikova
- Principal Investigator Email
- jurikova.lenka@fnbrno.cz
- Contact Person Name
- Lenka Jurikova
- Contact Person Email
- jurikova.lenka@fnbrno.cz
- Site Name
- Fakultni Nemocnice V Motole
- Principal Investigator Name
- Jana Haberlova
- Principal Investigator Email
- jana.haberlova@fnmotol.cz
- Contact Person Name
- Jana Haberlova
- Contact Person Email
- jana.haberlova@fnmotol.cz
Sponsor
Primary sponsor
- Full Name
- Biohaven Pharmaceuticals Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- ATOM International Limited
- Responsibilities
- Raters' trainings
- Name
- Clario
- Responsibilities
- DXA examination assessment
- Name
- Clario
- Responsibilities
- Cardiac safety monitoring (ECG)
- Name
- Suvoda LLC
- Name
- eResearchTechnology GmbH
- Responsibilities
- Spirometry central assessment
- Name
- Ppd Inc.
- Name
- Eurofins Central Laboratory B.V.
- Name
- Fulgent Genetics Inc.
- Name
- PCI Pharma Services Germany GmbH
- Name
- Rho Inc.
- Name
- Dokumeds SIA
- Name
- Scout Clinical
- Responsibilities
- Patient Concierge Services
- Name
- Chillibean Limited
- Responsibilities
- Video Recording Central Storage
Third parties
- {"country":"United Kingdom","full_name":"ATOM International Limited","duties_or_roles":"Raters' trainings","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Clario","duties_or_roles":"DXA examination assessment","organisation_type":"Industry"}
- {"country":"United States","full_name":"Clario","duties_or_roles":"Cardiac safety monitoring (ECG)","organisation_type":"Industry"}
- {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
- {"country":"Germany","full_name":"eResearchTechnology GmbH","duties_or_roles":"Spirometry central assessment","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient Concierge Services","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"United Kingdom","full_name":"Chillibean Limited","duties_or_roles":"Video Recording Central Storage","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Ppd Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"France","full_name":"MFM Aide Aux Familles D'Enfants Handicapes Moteurs","duties_or_roles":"MFM-32 scale","organisation_type":"Health care"}
- {"country":"Netherlands","full_name":"Eurofins Central Laboratory B.V.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Fulgent Genetics Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Rho Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"Latvia","full_name":"Dokumeds SIA","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Taldefgrobep
- Active Substance
- TALDEFGROBEP ALFA
- Modality
- Peptide/protein/enzyme
- Routes Of Administration
- SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
- Route
- SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
- Orphan Designation
- Yes
- Starting Dose
- 35 mg
- Dose Levels
- 35 mg
- Maximum Dose
- 35 mg
- Investigational Product Name
- Taldefgrobep
- Active Substance
- TALDEFGROBEP ALFA
- Modality
- Peptide/protein/enzyme
- Routes Of Administration
- SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
- Route
- SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
- Orphan Designation
- Yes
- Starting Dose
- 50 mg
- Dose Levels
- 50 mg
- Maximum Dose
- 50 mg
- Combination Treatment
- Yes
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