Clinical trial • Phase II • Neurology
risdiplam for Spinal muscular atrophy
Phase II trial of risdiplam for Spinal muscular atrophy. open-label, none/not specified-controlled, adaptive. 8 participants.
Overview
- Trial Therapeutic Area
- Neurology
- Trial Disease
- Spinal muscular atrophy
- Trial Stage
- Phase II
- Drug Modality
- Small molecule
- Paediatric Trial
- Yes
Key dates
- Initial CTIS Submission Date
- 20-07-2023
- First CTIS Authorization Date
- 06-02-2024
Trial design
open-label, none/not specified-controlled, adaptive Phase II trial across 10 sites in Italy, Belgium, Germany and others.
- Open Label
- Yes
- Comparator
- None/Not specified
- Adaptive
- True, dose may be adjusted during the study upon review of PK data
- Target Sample Size
- 8
- Trial Duration For Participant
- 28
Eligibility
Recruits 8 paediatric patients.
- Vulnerable Population
- Vulnerable population: newborn infants (neonates). Informed consent must be obtained from parent/caregiver prior to first study screening assessment; consent may be obtained after prenatal diagnosis and before participant's birth. Subject information and informed consent forms are provided for parents and breastfeeding partners (multiple ICF documents listed). No assent procedures for minors are specified in the available text.
Inclusion criteria
- {"criterion_text":"- Male or female newborn infant aged <20 days at first dose.\n- Newborn infants with genetic diagnosis of 5q-autosomal recessive SMA or newborn infants identified as positive for SMA via newborn screening or via prenatal testing.\n- Gestational age equal to or greater than 37 weeks.\n- Receiving adequate nutrition and hydration at the time of screening.\n- Adequately recovered from any acute illness at baseline and considered well enough to participate in the study.\n- Parent/caregiver is willing to consider nasogastric, nasojejunal, or gastrostomy tube placement during the study to maintain safe hydration, nutrition, and treatment delivery, if recommended by the investigator."}
Exclusion criteria
- {"criterion_text":"- Presence of clinical symptoms or signs consistent with SMA Type 0.\n- In the opinion of the investigator, inadequate venous or capillary blood access for the study procedures.\n- Systolic blood pressure or diastolic blood pressure or heart rate abnormalities or presence of clinically relevant electrocardiogram (ECG) abnormalities.\n- The infant (or the person breastfeeding the infant) taking any of the following: any inhibitor of CYP3A4 taken within 2 weeks (or within 5 times the elimination half-life, whichever is longer) prior to dosing, any inducer of CYP3A4 taken within 4 weeks (or within 5 times the elimination half-life, whichever is longer prior to dosing, and/or use of any multidrug and toxin extrusion (MATE) substrates taken within 2 weeks (or within 5 times the elimination half-life, whichever is longer) prior to dosing.\n- Concurrent or previous administration of nusinersen or onasemnogene abeparvovec.\n- Clinically significant abnormalities in laboratory test."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Plasma concentration of risdiplam and metabolite(s) as applicable at specified timepoints\n- AUC\n- Concentration at the end of a dosing interval to assess steady-state\n- Other PK parameters as appropriate\n- Risdiplam free fraction\n- Incidence and severity of adverse events, with severity determined according to the NCI CTCAE v5.0\n- Incidence and severity of serious adverse events\n- Incidence of treatment discontinuation due to adverse events\n- Incidence of abnormal laboratory values\n- Incidence of abnormal ECG values\n- Vital signs abnormalities, including body temperature, systolic and diastolic blood pressure, heart rate, respiratory rate\n- Physical examination, including detailed examination of the skin and mouth","definition_or_measurement_approach":"PK measurements: plasma concentrations of risdiplam and metabolites at specified timepoints; AUC and other PK parameters and concentration at end of dosing interval to assess steady-state. Risdiplam free fraction measured in plasma. Safety assessments: incidence and severity of adverse events graded using NCI CTCAE v5.0; incidence of serious adverse events; treatment discontinuations due to AEs; abnormal laboratory values and abnormal ECG values recorded by clinical laboratory and ECG assessments; vital signs measured (temperature, blood pressure, heart rate, respiratory rate); physical examinations including skin and mouth."}
Recruitment
- Digital Remote Recruitment
- True, PatientGO app and associated digital materials (EULA, Privacy Policy, Payment card) and PatientGO supplemental ICFs are listed among subject information materials indicating a digital/remote participant engagement platform
- Planned Sample Size
- 8
- Recruitment Window Months
- 31
- Consent Approach
- Informed consent must be obtained from the parent/caregiver prior to the first study screening assessment; consent may be obtained after prenatal diagnosis and before the participant's birth. Subject information and informed consent forms are provided for parents and for breastfeeding partners. No separate assent process for infants is described.
Methods
- K1_Recruitment arrangements documents present (country-specific K1 documents listed) - recruitment arrangements documentation available for multiple Member States.
- GP Letter (L2 Other subject information material GP Letter) - use of primary care/GP letters as recruitment/support material (document listed).
- PatientGO App materials (PatientGO App Copy, PatientGO EULA, PatientGO Payment card, PatientGO Privacy Policy) - use of PatientGO digital platform for participant engagement / administration (documents listed).
- Mobile Nursing materials (L1_SIS and ICF Mobile Nursing) - provision of mobile nursing services as described in study documents (documents listed).
- Travel and Reimbursement Policy and Payment card documents to support participant participation (documents listed).
Geography
- Total Number Of Sites
- 10
- Total Number Of Participants
- 8
Italy
- Earliest CTIS Part Ii Submission Date
- 18-07-2023
- Latest Decision Or Authorization Date
- 26-03-2026
- Processing Time Days
- 982
- Number Of Sites
- 2
- Number Of Participants
- 1
Sites
- Site Name
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Department Name
- Department of Women’s Child and Public Health Sciences
- Contact Person Name
- Eugenio Maria Mercuri
- Contact Person Email
- eugeniomaria.mercuri@policlinicogemelli.it
- Site Name
- Centro Clinico Nemo
- Department Name
- Nemo Center in Milan
- Contact Person Name
- Valeria Sansone
- Contact Person Email
- valeria.sansone@centrocliniconemo.it
Belgium
- Earliest CTIS Part Ii Submission Date
- 16-02-2024
- Latest Decision Or Authorization Date
- 30-01-2026
- Processing Time Days
- 714
- Number Of Sites
- 3
- Number Of Participants
- 2
Sites
- Site Name
- Centre Hospitalier Regional De La Citadelle
- Department Name
- Pediatric neurology
- Contact Person Name
- Aurore Daron
- Contact Person Email
- Aurore.daron@chrcitadelle.be
- Site Name
- Association Hospitaliere De Bruxelles Hopital Universitaire Des Enfants Reine Fabiola
- Department Name
- Pediatric neurology
- Contact Person Name
- Pauline Dontaine
- Contact Person Email
- Pauline.dontaine@huderf.be
- Site Name
- Antwerp University Hospital
- Department Name
- Pediatric neurology
- Contact Person Name
- Diane Deysen
- Contact Person Email
- Diane.beysen@uza.be
Germany
- Earliest CTIS Part Ii Submission Date
- 29-01-2024
- Latest Decision Or Authorization Date
- 26-03-2026
- Processing Time Days
- 787
- Number Of Sites
- 1
- Number Of Participants
- 2
Sites
- Site Name
- Universitaetsklinikum Essen AöR
- Department Name
- Department of Pediatrics I
- Contact Person Name
- Heike Koelbel
- Contact Person Email
- Heike.Koelbel@uk-essen.de
Poland
- Earliest CTIS Part Ii Submission Date
- 13-02-2024
- Latest Decision Or Authorization Date
- 26-03-2026
- Processing Time Days
- 772
- Number Of Sites
- 2
- Number Of Participants
- 1
Sites
- Site Name
- Instytut Pomnik Centrum Zdrowia Dziecka
- Department Name
- Department of Neurology and Epileptology
- Contact Person Name
- Katarzyna Kotulska-Jozwiak
- Contact Person Email
- K.Kotulska@IPCZD.PL
- Site Name
- Uniwersyteckie Centrum Kliniczne
- Department Name
- Klinika Neurologii Rozwojowej
- Contact Person Name
- Maria Mazurkiewicz-Beldzinska
- Contact Person Email
- mmazur@gumed.edu.pl
Netherlands
- Earliest CTIS Part Ii Submission Date
- 29-02-2024
- Latest Decision Or Authorization Date
- 26-03-2026
- Processing Time Days
- 756
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- Universitair Medisch Centrum Utrecht
- Department Name
- Department of Neurology & Neurosurgery
- Contact Person Name
- Ludo van der Pol
- Contact Person Email
- W.L.vanderPol@umcutrecht.nl
Norway
- Earliest CTIS Part Ii Submission Date
- 02-02-2024
- Latest Decision Or Authorization Date
- 30-01-2026
- Processing Time Days
- 728
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- Oslo University Hospital HF
- Department Name
- Pediatric Department for Neurosciences
- Contact Person Name
- Sean Ciaran Wallace
- Contact Person Email
- seawal@ous-hf.no
Sponsor
Primary sponsor
- Full Name
- F. Hoffmann-La Roche AG
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Switzerland
Contract research organisations
- Name
- Syneos Health Netherlands B.V.
- Responsibilities
- Global CRO
Third parties
- {"country":"Netherlands","full_name":"Syneos Health Netherlands B.V.","duties_or_roles":"Global CRO","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Other Third Party Duty","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- RO7034067
- Active Substance
- risdiplam
- Modality
- Small molecule
- Routes Of Administration
- ORAL; NASOGASTRIC TUBE OR PERCUTANEOUS ENDOSCOPIC GASTROSTOMY TUBE USE
- Route
- oral (or via nasogastric/nasojejunal/gastrostomy tube)
- Authorisation Status
- prodAuthStatus: 1 (no marketing authorisation indicated)
- Starting Dose
- 0.15 mg/kg once daily
- Dose Levels
- 0.15 mg/kg
- Frequency
- once daily
- Maximum Dose
- maxDailyDoseAmount 0.15 mg/kg; maxTotalDoseAmount 1 mg/kg (per product record)
- Dose Escalation Increase
- Initial dose 0.15 mg/kg; dose may be adjusted during the study upon review of PK data.
- Investigational Product Name
- Evrysdi 0.75 mg/mL powder for oral solution
- Active Substance
- risdiplam
- Modality
- Small molecule
- Routes Of Administration
- ORAL; NASOGASTRIC TUBE OR PERCUTANEOUS ENDOSCOPIC GASTROSTOMY TUBE USE
- Route
- oral (or via nasogastric/nasojejunal/gastrostomy tube)
- Authorisation Status
- Marketing authorisation present: marketingAuthNumber EU/1/21/1531/001; prodAuthStatus: 2
- Starting Dose
- 0.15 mg/kg once daily
- Dose Levels
- 0.15 mg/kg
- Frequency
- once daily
- Maximum Dose
- maxDailyDoseAmount 0.15 mg/kg; maxTotalDoseAmount 1 mg/kg (per product record)
- Dose Escalation Increase
- Initial dose 0.15 mg/kg; dose may be adjusted during the study upon review of PK data.
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