Angelman SyndromePhase 1NCT04428281
A Study to Investigate the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of RO7248824 in Participants With Angelman Syndrome (AS)
A Phase 1 study testing RO7248824 in people with Angelman Syndrome, run by Hoffmann-La Roche at 12 sites in 4 countries.
Trial summary
This is a phase I, multicenter, non-randomized, adaptive, open-label, multiple ascending, intra-participant, dose-escalation study with a long-term extension (LTE) part and an optional open-label extension (OOE) part. Read more about this study
- Who is it for?
- Ages 1 year to 12 years
- Conditions the study is for
- Angelman Syndrome
- What is being tested?
- RO7248824
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 12 sitesin 4 countries
- Study dates
- 19 Aug 2020to 31 Jul 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
- A caregiver must be able to consent for the participant according to International Council on Harmonisation (ICH) and local regulations.
- Ability to comply with all study requirements.
- Have adequate supportive psychosocial circumstances.
- Able to tolerate blood draws.
- Able to undergo lumbar puncture (LP) and IT injection, under sedation or anesthesia if needed and as determined appropriate by the Investigator.
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- Stable medical status for at least 4 weeks prior to Screening and at the time of enrollment.
- Body weight of ≥ 7 kg
- Participant must be ≥ 1 to ≤ 12 years of age at the time of signing of the informed consent by the caregiver.
- Clinical diagnosis of AS confirmed by a molecular diagnosis with genotypic classification of either Ubiquitin-protein ligase E3A (UBE3A) mutation of the maternal allele or deletion on the maternally inherited chromosome 15q11q13 that includes the UBE3A gene and is less than 7 megabyte (Mb) in size.
- Reproductive Status:
- Some of the provisions that follow may have limited applicability based on the age range of study participants (i.e., up to the age of 12) and the nature of the disease understudy. These provisions are nonetheless included for purposes of completeness in order:
- Female Participants
- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
- Women of non-childbearing potential.
- Women of childbearing potential who agree to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods during the treatment period and for at least 6 months after the final dose of RO7248824 (RG6091). The following are acceptable contraceptive methods: bilateral tubal occlusion/ ligation, male sexual partner who is sterilized, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices and copper intrauterine devices, male or female condom with or without spermicide; and cap, diaphragm, or sponge with spermicide.
- Male Participants
- During the treatment period and for at least 6 months after the final dose of RO7248824 (RG6091), consent has to be provided to:
- Remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures such as a condom, with a female partner of childbearing potential, or pregnant female partner, to avoid exposing the embryo.
- The reliability of sexual abstinence for male and/or female enrollment eligibility needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of preventing drug exposure.
- Current or prior participations in the LTE part of Study BP41674.
Who cannot join
- Diagnostic Assessments
- Clinically-significant laboratory, vital sign or electrocardiography (ECG) abnormalities at Screening
- Type of Participants and Disease Characteristics
- Molecular diagnosis of AS with genotypic classification: Paternal Uniparental Disomy (UPD) of 15q11-13; UBE3A Imprinting center defect (ID); A partial molecular diagnosis of AS, that cannot exclude (UPD)or ID despite appropriate genetic testing.
- Clinically relevant hematological, hepatic, cardiac or renal disease or event, in the judgement of the Investigator.
- Any concomitant condition that might interfere with the clinical evaluation of AS and that is not related to AS.
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- 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.
- A medical history of brain or spinal disease that would interfere with the LP process, CSF circulation or safety assessment
- History of clinically significant post-lumbar-puncture headache of moderate or severe intensity and/or blood patch
- Malignancy within 5 years of Screening
- Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study
- Have any other conditions, which, in the opinion of the Investigator, would make the participant unsuitable for inclusion or could interfere with the participant participating in or completing the study, including any contraindication to administration of intrathecal therapy.
- Premature birth with gestational age at birth below 34 weeks.
- History of hypersensitivity to the investigational medicinal product (IMP), antisense oligonucleotides, or any excipients.
- Prior Therapy
- Allowed sleep medications have not been stable for 4 weeks prior to screening and at the time of enrollement.
- Allowed medications for treatment of epilepsy have not been stable for 12 weeks prior to screening and at the time of enrollment.
- Use of antiplatelet or anticoagulant therapy for 2 weeks prior to screening and at the time of enrollment.
- Concurrent psychotropic medications have not been stable for 4 weeks prior to screening and at the time of enrollment.
- Other Exclusion Criteria: Prior/Concurrent Clinical Study Experience
- Received an investigational drug within 90 days or 5 times the half-life of the investigational drug (whichever is longer) or participation in a study testing an investigational medical device within 90 days prior to first dosing or if the device is still active.
- Concurrent or planned concurrent participation in any clinical study (including observational, non-drug and non-interventional studies) without a signed data sharing agreement in place between the other clinical study and the Sponsor.
- Previous participation in a cellular therapy, or gene therapy, or gene editing clinical study.
- Participants who never enrolled in Study BP41674, or who discontinued participation due to safety reasons, are not eligible for the OOE part.
Trial locations and contacts
12 sites in 4 countries.
12 sites in 4 countries
United States7 sites
Carolina Institute for Development DisabilitiesUniversity of North Carolina/School of Medicine
Carrboro, North Carolina, 27510
Rush Medical Center
Chicago, Illinois, 60612
Baylor College of Med
Houston, Texas, 77030
UCLA Neuropsychiatric Institute
Los Angeles, California, 90024
Columbia University Medical Center
New York, New York, 10032
Mayo Clinic - Rochester
Rochester, Minnesota, 55905
Rady Children's Hospital - San Diego
San Diego, California, 92123
Spain3 sites
Hospital Sant Joan De Deu
Esplugues de Llobregas, Barcelona, 08950
Corporacio Sanitaria Parc Tauli
Sabadell, Barcelona, 08208
Hospital Universitario Virgen del Rocío
Seville, 41013
Netherlands1 site
Erasmus MC / location Sophia Kinderziekenhuis
Rotterdam, 3015 GJ
About this study
Official title: An Open-label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7248824 in Participants With Angelman Syndrome
This is a phase I, multicenter, non-randomized, adaptive, open-label, multiple ascending, intra-participant, dose-escalation study with a long-term extension (LTE) part and an optional open-label extension (OOE) part. The objective of the study is to investigate the safety, tolerability, PK and PD of RO7248824 administered intrathecally (IT) in participants with AS. Two linked sets of dose escalation cohorts are planned based on two different age groups, namely participants with AS aged ≥ 5 to ≤ 12 years in cohorts A1 to A5 (with at least 2 participants ≤ 8 years old in each cohort) and AS participants aged ≥ 1 to ≤ 4 years in cohorts B1 to B5. The two sets of cohorts will be run in parallel, with each cohort A1 to A5 preceding and gating the linked cohort B1 to B5 (e.g., A1 precedes B1).
- Conditions
- Angelman Syndrome
- Being tested
- RO7248824
- Keywords
- RO7248824; Angelman; ASO; LNA; Angelman syndrome
- Medical subject headings
- Angelman Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RO7248824Drug
In the MAD part, RO7248824 will be administered as IT injection of varing dose levels over a period of 8 weeks, with a minimum of approximately 4 weeks between each dose administration. In the LTE part, RO7248824 will be administered as IT injection of varying dose levels over a period of 144 weeks, with a minimum of approximately 16 weeks between each dose administration. In the OOE part, participants will receive RO7248824 as an IT injection with the same dosing regime as the LTE part over a period of up to 48 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A1 RO7248824 | Experimental | Participants 5-12 years Receives: Drug: RO7248824 |
| Cohort A2 RO7248824 | Experimental | Participants 5-12 years Receives: Drug: RO7248824 |
| Cohort A3 RO7248824 | Experimental | Participants 5-12 years Receives: Drug: RO7248824 |
| Cohort A4 RO7248824 | Experimental | Participants 5-12 years Receives: Drug: RO7248824 |
| Cohort A5 RO7248824 | Experimental | Participants 5-12 years Receives: Drug: RO7248824 |
| Cohort B1 RO7248824 | Experimental | Participants 1-4 years Receives: Drug: RO7248824 |
| Cohort B2 RO7248824 | Experimental | Participants 1-4 years Receives: Drug: RO7248824 |
| Cohort B3 RO7248824 | Experimental | Participants 1-4 years Receives: Drug: RO7248824 |
| Cohort B4 RO7248824 | Experimental | Participants 1-4 years Receives: Drug: RO7248824 |
| Cohort B5 RO7248824 | Experimental | Participants 1-4 years Receives: Drug: RO7248824 |
| LTE: Cohort EA1 RO7248824 | Experimental | New participants (age 5-12) enrolling directly in the LTE part Receives: Drug: RO7248824 |
| LTE: Cohort EA2 RO7248824 | Experimental | Participants continuing from multiple ascending dose (MAD) cohorts A1 and A2 Receives: Drug: RO7248824 |
| LTE: Cohort EA3 RO7248824 | Experimental | Participants continuing from MAD cohorts A3 and A4 Receives: Drug: RO7248824 |
| LTE: Cohort EA4 RO7248824 | Experimental | Participants continuing from MAD Cohort A5 Receives: Drug: RO7248824 |
| LTE: Cohort EB1 RO7248824 | Experimental | New participants (age 1-4) enrolling directly into the LTE Receives: Drug: RO7248824 |
| LTE: Cohort EB2 RO7248824 | Experimental | Participants continuing from MAD cohorts B1 and B2 Receives: Drug: RO7248824 |
| LTE: Cohort EB3 RO7248824 | Experimental | Participants continuing from MAD cohorts B3 and B4 Receives: Drug: RO7248824 |
| LTE: Cohort EB4 RO7248824 | Experimental | Participants continuing from MAD Cohort B5 Receives: Drug: RO7248824 |
| OOE: RO7248824 | Experimental | Participants in the LTE part of the study will be given the opportunity to participate in the OOE part. Receives: Drug: RO7248824 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency and Severity of Adverse Events (AEs)
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal.
LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
OOE part: From baseline OOE visit to final OOE visit (Day 420) or early termination.
Measured: Baseline to last visit or early withdrawal
Frequency and Severity of Serious Adverse Events (SAEs)
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal.
LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
OOE part: From baseline OOE visit to final OOE visit (Day 420) or early termination.
Measured: Baseline to last visit or early withdrawal
Number of Participants Discontinued Treatment due to AEs
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal.
LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
OOE part: From baseline OOE visit to final OOE visit (Day 420) or early termination.
Measured: Baseline to last visit or early withdrawal
Frequency of Abnormal Laboratory Findings (Blood, Cerebrospinal Fluid [CSF] and Urinalysis)
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal.
LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
OOE part: From baseline OOE visit to final OOE visit (Day 420) or early termination.
Measured: Baseline to last visit or early withdrawal
Frequency of Abnormal Vital Signs
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal.
LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
Measured: Baseline to last visit or early withdrawal
Frequency of Abnormal Electrocardiography (ECG) Values
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal.
LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
Measured: Baseline to last visit or early withdrawal
Mean Changes From Baseline in Temperature Over Time
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal.
LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
Measured: Baseline to last visit or early withdrawal
Mean Changes From Baseline in Systolic Blood Pressure Over Time
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal.
LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
Measured: Baseline to last visit or early withdrawal
Mean Changes From Baseline in Diastolic Blood Pressure Over Time
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal.
LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
Measured: Baseline to last visit or early withdrawal
Mean Changes From Baseline in Heartrate Over Time
MAD part: From the baseline MAD visit to the final MAD visit (D365) or early withdrawal.
LTE part: From the baseline LTE visit to final LTE visit (D1092) or early withdrawal.
Measured: Baseline to last visit or early withdrawal
Mean Changes From Baseline in Respiratory Rate Over Time
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal.
LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
Measured: Baseline to last visit or early withdrawal
Secondary outcomes (4)
Time to Maximum Concentration (Tmax) for RO7248824
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal.
LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
Measured: Baseline to last visit or early withdrawal
Maximum Plasma Concentration Observed (Cmax) for RO7248824
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal.
LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
Measured: Baseline to last visit or early withdrawal
Area Under Curve (AUC) From Time 0 to Time of Last Sampling Point or Last Quantifiable Sample, Whichever Comes First (AUC last) for RO7248824
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal.
LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
Measured: Baseline to last visit or early withdrawal
AUC From Time 0 to Infinity (AUCinf) for RO7248824
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal.
LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
Measured: Baseline to last visit or early withdrawal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start19 Aug 2020
- Primary completion31 Jul 2025
- Study completion31 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Angelman SyndromeStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Non-randomized, adaptive, open label, multiple ascending, intra-participant, dose-escalation study
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04428281
- Sponsor's protocol ID
- BP41674
- Other IDs
- 2019-003787-48, RG6091, 2019
- Status last verified
- Aug 2025
- First submitted
- 9 Jun 2020
- Last updated
- 24 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).
Publications
Hipp JF, Bacino CA, Bird LM, Bruenig-Traebert I, Chan D, de Wit MC, Fontoura P, Hooper G, Jagasia R, Krishnan ML, Murtagh L, Noci A, Martinez AR, Schwab D, Serrano M, Shen MD, Tillmann J, Tjeertes J, Vincenzi B, Berry-Kravis E, Bonni A; Rugonersen Study Group; all TANGELO investigators. The UBE3A-ATS antisense oligonucleotide rugonersen in children with Angelman syndrome: a phase 1 trial. Nat Med. 2025 Sep;31(9):2936-2945. doi: 10.1038/s41591-025-03784-7. Epub 2025 Jul 11.
PubMed 40646322
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7248824 in Participants With Angelman Syndrome
- ClinicalTrials.gov ID
- NCT04428281
- Acronym / sponsor ID
- BP41674
- Conditions
- Angelman Syndrome
- Keywords
- RO7248824; Angelman; ASO; LNA; Angelman syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 19 Aug 2020 (actual)
- Primary completion
- 31 Jul 2025 (actual)
- Study completion
- 31 Jul 2025 (actual)
- First posted
- 11 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase I, multicenter, non-randomized, adaptive, open-label, multiple ascending, intra-participant, dose-escalation study with a long-term extension (LTE) part and an optional open-label extension (OOE) part. The objective of the study is to investigate the safety, tolerability, PK and PD of RO7248824 administered intrathecally (IT) in participants with AS. Two linked sets of dose escalation cohorts are planned based on two different age groups, namely participants with AS aged ≥ 5 to ≤ 12 years in cohorts A1 to A5 (with at least 2 participants ≤ 8 years old in each cohort) and AS participants aged ≥ 1 to ≤ 4 years in cohorts B1 to B5. The two sets of cohorts will be run in parallel, with each cohort A1 to A5 preceding and gating the linked cohort B1 to B5 (e.g., A1 precedes B1).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 19
- Model description
- Non-randomized, adaptive, open label, multiple ascending, intra-participant, dose-escalation study
| Arm | Type | Receives |
|---|---|---|
| Cohort A1 RO7248824 | Experimental | Drug: RO7248824Participants 5-12 years |
| Cohort A2 RO7248824 | Experimental | Drug: RO7248824Participants 5-12 years |
| Cohort A3 RO7248824 | Experimental | Drug: RO7248824Participants 5-12 years |
| Cohort A4 RO7248824 | Experimental | Drug: RO7248824Participants 5-12 years |
| Cohort A5 RO7248824 | Experimental | Drug: RO7248824Participants 5-12 years |
| Cohort B1 RO7248824 | Experimental | Drug: RO7248824Participants 1-4 years |
| Cohort B2 RO7248824 | Experimental | Drug: RO7248824Participants 1-4 years |
| Cohort B3 RO7248824 | Experimental | Drug: RO7248824Participants 1-4 years |
| Cohort B4 RO7248824 | Experimental | Drug: RO7248824Participants 1-4 years |
| Cohort B5 RO7248824 | Experimental | Drug: RO7248824Participants 1-4 years |
| LTE: Cohort EA1 RO7248824 | Experimental | Drug: RO7248824New participants (age 5-12) enrolling directly in the LTE part |
| LTE: Cohort EA2 RO7248824 | Experimental | Drug: RO7248824Participants continuing from multiple ascending dose (MAD) cohorts A1 and A2 |
| LTE: Cohort EA3 RO7248824 | Experimental | Drug: RO7248824Participants continuing from MAD cohorts A3 and A4 |
| LTE: Cohort EA4 RO7248824 | Experimental | Drug: RO7248824Participants continuing from MAD Cohort A5 |
| LTE: Cohort EB1 RO7248824 | Experimental | Drug: RO7248824New participants (age 1-4) enrolling directly into the LTE |
| LTE: Cohort EB2 RO7248824 | Experimental | Drug: RO7248824Participants continuing from MAD cohorts B1 and B2 |
| LTE: Cohort EB3 RO7248824 | Experimental | Drug: RO7248824Participants continuing from MAD cohorts B3 and B4 |
| LTE: Cohort EB4 RO7248824 | Experimental | Drug: RO7248824Participants continuing from MAD Cohort B5 |
| OOE: RO7248824 | Experimental | Drug: RO7248824Participants in the LTE part of the study will be given the opportunity to participate in the OOE part. |
Who may qualify
- Ages
- 1 year to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (21 listed)
- 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.
- A caregiver must be able to consent for the participant according to International Council on Harmonisation (ICH) and local regulations.
- Ability to comply with all study requirements.
- Have adequate supportive psychosocial circumstances.
- Able to tolerate blood draws.
Key exclusion criteria (26 listed)
- Diagnostic Assessments
- Clinically-significant laboratory, vital sign or electrocardiography (ECG) abnormalities at Screening
- Type of Participants and Disease Characteristics
- Molecular diagnosis of AS with genotypic classification: Paternal Uniparental Disomy (UPD) of 15q11-13; UBE3A Imprinting center defect (ID); A partial molecular diagnosis of AS, that cannot exclude (UPD)or ID despite appropriate genetic testing.
- Clinically relevant hematological, hepatic, cardiac or renal disease or event, in the judgement of the Investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RO7248824In the MAD part, RO7248824 will be administered as IT injection of varing dose levels over a period of 8 weeks, with a minimum of approximately 4 weeks between each dose administration. In the LTE part, RO7248824 will be administered as IT injection of varying dose levels over a period of 144 weeks, with a minimum of approximately 16 weeks between each dose administration. In the OOE part, participants will receive RO7248824 as an IT injection with the same dosing regime as the LTE part over a period of up to 48 weeks. | Drug | Cohort A1 RO7248824, Cohort A2 RO7248824, Cohort A3 RO7248824, Cohort A4 RO7248824, Cohort A5 RO7248824, Cohort B1 RO7248824, Cohort B2 RO7248824, Cohort B3 RO7248824, Cohort B4 RO7248824, Cohort B5 RO7248824, LTE: Cohort EA1 RO7248824, LTE: Cohort EA2 RO7248824, LTE: Cohort EA3 RO7248824, LTE: Cohort EA4 RO7248824, LTE: Cohort EB1 RO7248824, LTE: Cohort EB2 RO7248824, LTE: Cohort EB3 RO7248824, LTE: Cohort EB4 RO7248824, OOE: RO7248824 |
Primary outcome
Frequency and Severity of Adverse Events (AEs)
Time frame: Baseline to last visit or early withdrawal
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal. LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal. OOE part: From baseline OOE visit to final OOE visit (Day 420) or early termination.
Frequency and Severity of Serious Adverse Events (SAEs)
Time frame: Baseline to last visit or early withdrawal
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal. LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal. OOE part: From baseline OOE visit to final OOE visit (Day 420) or early termination.
Number of Participants Discontinued Treatment due to AEs
Time frame: Baseline to last visit or early withdrawal
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal. LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal. OOE part: From baseline OOE visit to final OOE visit (Day 420) or early termination.
Frequency of Abnormal Laboratory Findings (Blood, Cerebrospinal Fluid [CSF] and Urinalysis)
Time frame: Baseline to last visit or early withdrawal
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal. LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal. OOE part: From baseline OOE visit to final OOE visit (Day 420) or early termination.
Frequency of Abnormal Vital Signs
Time frame: Baseline to last visit or early withdrawal
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal. LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
Frequency of Abnormal Electrocardiography (ECG) Values
Time frame: Baseline to last visit or early withdrawal
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal. LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
Mean Changes From Baseline in Temperature Over Time
Time frame: Baseline to last visit or early withdrawal
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal. LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
Mean Changes From Baseline in Systolic Blood Pressure Over Time
Time frame: Baseline to last visit or early withdrawal
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal. LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
Mean Changes From Baseline in Diastolic Blood Pressure Over Time
Time frame: Baseline to last visit or early withdrawal
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal. LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
Mean Changes From Baseline in Heartrate Over Time
Time frame: Baseline to last visit or early withdrawal
MAD part: From the baseline MAD visit to the final MAD visit (D365) or early withdrawal. LTE part: From the baseline LTE visit to final LTE visit (D1092) or early withdrawal.
Mean Changes From Baseline in Respiratory Rate Over Time
Time frame: Baseline to last visit or early withdrawal
MAD part: From the baseline MAD visit to the final MAD visit (Day 365) or early withdrawal. LTE part: From the baseline LTE visit to final LTE visit (Day 1092) or early withdrawal.
4 secondary outcomes
Time to Maximum Concentration (Tmax) for RO7248824
Time frame: Baseline to last visit or early withdrawal
Maximum Plasma Concentration Observed (Cmax) for RO7248824
Time frame: Baseline to last visit or early withdrawal
Area Under Curve (AUC) From Time 0 to Time of Last Sampling Point or Last Quantifiable Sample, Whichever Comes First (AUC last) for RO7248824
Time frame: Baseline to last visit or early withdrawal
AUC From Time 0 to Infinity (AUCinf) for RO7248824
Time frame: Baseline to last visit or early withdrawal
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2025.
- Derived from this study: PubMed 40646322Hipp JF, Bacino CA, Bird LM, Bruenig-Traebert I, Chan D, de Wit MC, Fontoura P, Hooper G, Jagasia R, Krishnan ML, Murtagh L, Noci A, Martinez AR, Schwab D, Serrano M, Shen MD, Tillmann J, Tjeertes J, Vincenzi B, Berry-Kravis E, Bonni A; Rugonersen Study Group; all TANGELO investigators. The UBE3A-ATS antisense oligonucleotide rugonersen in children with Angelman syndrome: a phase 1 trial. Nat Med. 2025 Sep;31(9):2936-2945. doi: 10.1038/s41591-025-03784-7. Epub 2025 Jul 11.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Related trials for Angelman Syndrome
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
12 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RO7248824 in people with Angelman Syndrome, run by Hoffmann-La Roche at 12 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Spain, Italy, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency and Severity of Adverse Events (AEs) (time frame: Baseline to last visit or early withdrawal). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04428281, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2025.