Overview
Sponsor-declared trial summary
Phase
Human pharmacology (Phase I) - Other
Status
Ended
Participants planned
53
Countries
3
Sites
5
Angelman Syndrome (AS)
To assess the safety and tolerability profile of RO7248824
Key facts
- Sponsor
- F. Hoffmann-La Roche AG
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10]
- Trial duration
- 25 Aug 2020 → 31 Jul 2025
- Decision date (initial)
- 2024-12-02
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- F. Hoffmann-La Roche Ltd
External identifiers
- EU CT number
- 2024-514797-45-00
- EudraCT number
- 2019-003787-48
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacokinetic, Others, Safety
To assess the safety and tolerability profile of RO7248824
Secondary objectives 1
- To investigate the plasma pharmacokinetics (PK) of RO7248824
Conditions and MedDRA coding
Angelman Syndrome (AS)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10049004 | Angelman's syndrome | 100000004850 |
Study design 3 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Multiple Ascending Dose Part Dose escalation steps within and across cohorts with a range of 15 to 240 mg for cohorts A1 to A5 and 6 to 240 mg for cohorts B1 to B5.
|
Not Applicable | None | cohorts A1 to A5.: 15 to 240 mg cohorts B1 to B5: 6 to 240 mg |
|
| 2 | Long-Term Extension Part After Multiple Ascending Dose Part
|
Not Applicable | None | “A” cohorts: Age ≥5 to ≤12 years ∙ Participants, enrolling directly into the LTE part of the study will be included in cohort EA1 and will receive 60 mg RO7248824 every 16 weeks. ∙ Participants from MAD cohorts A1 and A2 may transition to Cohort EA2 and will receive 120 mg RO7248824 every 16 weeks. ∙ Participants from MAD cohorts A3 and A4 may transition to Cohort EA3 and will receive 180 mg RO7248824 every 24 weeks. ∙ Participants from MAD cohort A5 may transition to Cohort EA4 and will receive 240 mg RO7248824 every 24 weeks. “B” cohorts: Age ≥ 1 to ≤ 4 years ∙ Participants, enrolling directly into the LTE part of the study will be included into cohort EB1 and will receive 60 mg RO7248824 every 16 weeks. ∙ Participants from cohorts B1 and B2 may transition to Cohort EB2 and will receive 120 mg RO7248824 every 16 weeks. ∙ Participants from cohorts B3 and B4 may transition to Cohort EB3 and will receive 180 mg RO7248824 every 24 weeks. ∙ Participants from MAD cohort B5 may transition to Cohort EB4 and will receive 240 mg RO7248824 every 24 weeks. |
|
| 3 | Optional Open-Label Extension Part The dose regimens administered during the OOE part will be the same dose(s) explored during the LTE part.
Participants should start the OOE part on the same dose and dosing interval as their last dose in the LTE part of the study, unless there is a need to reduce the dose for safety or tolerability reasons.
|
Not Applicable | None |
Regulatory references
- Scientific advice from competent authorities
- European Medicines Agency
- Plan to share IPD
- No
- IPD plan description
- N/A
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- The participant has a parent, caregiver or legal representative (hereinafter “caregiver”) who is reliable, competent and at least 18 years of age. The caregiver is willing and able to accompany the participant to clinic visits and to be available to the Investigational Site by phone or email if needed and who (in the opinion of the investigator) is and will remain sufficiently knowledgeable of participant’s ongoing condition to respond to any inquiries about the participant from personnel from the Study Site
- Clinical diagnosis of AS confirmed by a molecular diagnosis with genotypic classification of either: ••Ubiquitin-protein ligase E3A (UBE3A) mutation of maternal allele Deletion on the maternally inherited chromosome 15q11q13 that includes the UBE3Agene and is less than 7 Mb in size
- Stable medical status for at least 4 weeks prior to Screening and at the time of enrollment
- Have adequate supportive psychosocial circumstances
- Able to tolerate blood draws
- Have adequate supportive psychosocial circumstances
Exclusion criteria 6
- Clinically relevant hematological, hepatic, cardiac, renal disease event, or laboratory abnormality, in the judgment of the Investigator
- Any concomitant condition that might interfere with the clinical evaluation of AS and that is not related to AS
- Known history of human immunodeficiency virus (HIV) or hepatitis B virus (HBV) or hepatitis C virus (HCV)
- Any condition that increases risk of meningitis
- History of bleeding diathesis or coagulopathy
- History of clinically significant post-lumbar-puncture headache of moderate or severe intensity and/or blood patch
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 4
- 1. Frequency and severity of adverse events, serious adverse events, treatment discontinuations due to adverse events (MAD, LTE, OOE)
- 2. Frequency of abnormal laboratory findings (blood and cerebrospinal fluid [CSF]) (MAD, LTE, OOE)
- 3. Frequency of abnormal vital signs and ECG values (MAD, LTE)
- 4. Mean changes from baseline in vital signs (temperature, systolic and diastolic blood pressure, heartrate, respiratory rate) over time (MAD, LTE)
Secondary endpoints 3
- 1. Time to maximum concentration (Tmax) (MAD, LTE, OOE)
- 2. Maximum plasma concentration observed (Cmax) (MAD, LTE, OOE)
- 3. AUC from Time 0 to time of last sampling point or last quantifiable sample, whichever comes first (AUClast), AUC from Time 0 to infinity (AUCinf) (MAD, LTE, OOE)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD7896660 · Product
- Active substance
- Rugonersen
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRATRACHEAL USE
- Authorisation status
- Not Authorised
- MA holder
- F. HOFFMANN-LA ROCHE LTD
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/20/2379
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
F. Hoffmann-La Roche AG
- Sponsor organisation
- F. Hoffmann-La Roche AG
- Address
- Grenzacherstrasse 124
- City
- Basel
- Postcode
- 4058
- Country
- Switzerland
Scientific contact point
- Organisation
- F. Hoffmann-La Roche AG
- Contact name
- Trial Information System - TISL
Public contact point
- Organisation
- F. Hoffmann-La Roche AG
- Contact name
- Trial Information System - TISL
Third parties 12
| Organisation | City, country | Duties |
|---|---|---|
| Clinical Outcomes Solutions LLC ORG-100045476
|
Tucson, United States | Other |
| Pharm Research Associates (UK) Limited ORG-100008833
|
Reading, United Kingdom | Other |
| Biotrial ORG-100006463
|
Rennes, France | Laboratory analysis |
| Eresearchtechnology Inc. ORG-100013039
|
Philadelphia, United States | Other |
| Endpoint Clinical Inc. ORG-100040567
|
San Francisco, United States | Interactive response technologies (IRT) |
| Siena Imaging S.r.l. ORG-100051846
|
Siena, Italy | Laboratory analysis |
| Bioclinica Inc. ORG-100033079
|
Princeton, United States | Laboratory analysis |
| Q Squared Solutions Limited ORG-100042527
|
Livingston, United Kingdom | Laboratory analysis |
| Greenphire LLC ORG-100041621
|
King Of Prussia, United States | Other |
| Syneos Health Netherlands B.V. ORG-100013861
|
Amsterdam, Netherlands | Data management |
| Cogstate Limited ORG-100044403
|
Melbourne, Australia | Other |
| Pharmaceutical Research Associates Group B.V. ORG-100006268
|
Assen, Netherlands | Laboratory analysis |
Locations
3 EU/EEA countries · 5 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ended | 8 | 1 |
| Netherlands | Ended | 10 | 1 |
| Spain | Ended | 10 | 3 |
| Rest of world
United States, Canada, United Kingdom
|
— | 25 | — |
Investigational sites
Ospedale Pediatrico Bambino Gesu
Dipartimento di Scienze Neurologiche e Psichiatriche, Piazza Di Sant'onofrio 4, 00165, Rome
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Pediaetric neurology, Dr. Molewaterplein 40, 3015 GD, Rotterdam
Parc Tauli Hospital Universitari
Child Neurology, Parc Del Tauli 1, 08208, Sabadell
University Hospital Virgen Del Rocio S.L.
Child Neurology, Avenida De Manuel Siurot S/n, 41013, Sevilla
Hospital Sant Joan De Deu Barcelona
Child Neurology, Passeig De Sant Joan De Deu 2, 08950, Esplugues De Llobregat
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2020-08-27 | 2025-06-27 | 2020-09-08 | 2022-06-28 | |
| Netherlands | 2021-01-05 | 2025-07-18 | 2021-01-08 | 2022-06-28 | |
| Spain | 2020-08-25 | 2025-07-02 | 2020-08-27 | 2022-06-28 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| BP41674 CTIS results summary SUM-116546
|
2026-01-27T14:18:06 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| Final Lay Person Summary results | 2026-01-29T16:09:32 | Submitted | Laypersons Summary of Results |
Documents 7 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | LPS_BP41674_TANGELO_Final results_09Dec2025_EN | 1 |
| Laypersons summary of results (for publication) | LPS_BP41674_TANGELO_Final results_09Dec2025_ESP_rev | 1 |
| Laypersons summary of results (for publication) | LPS_BP41674_TANGELO_Final results_09Dec2025_NL-NL_final | 1 |
| Laypersons summary of results (for publication) | LPS_BP41674_TANGELO_Final-results_09Dec2025_EN-1_it_IT | 1 |
| Protocol (for publication) | d1_protocol-2024-514797-45-00-redacted | 10 |
| Summary of results (for publication) | BP41674_ CTIS Final Results | N/A |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_eng_2024-514797-45-00 | N/A |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-09-11 | Netherlands | Acceptable with conditions 2024-10-10
|
2024-10-10 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-12-11 | Netherlands | Acceptable with conditions 2024-10-10
|
2024-12-11 |