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A Study To Investigate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of RO7248824 In Participants With Angelman Syndrome

Primary Purpose

Angelman Syndrome

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
RO7248824
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Angelman Syndrome focused on measuring RO7248824; Angelman; ASO; LNA; Angelman syndrome

Eligibility Criteria

1 Year - 12 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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 LP and IT injection, under sedation or anesthesia if needed and as determined appropriate by the Investigator.
  • 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 UBE3A mutation of the maternal allele or deletion on the maternally inherited chromosome 15q11q13 that includes the UBE3A gene and is less than 7 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.

Exclusion Criteria:

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:

UBE3A missense mutation of maternal allele 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.

Medical history and concurrent disease

  • Clinically relevant hematological, hepatic, cardiac or renal disease or event, in the judgement of the investigator. Pre-existing abnormal hepatic, renal or hematology lab tests must be discussed with the Sponsor Medical Monitor.
  • 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.
  • A medical history of brain or spinal disease that would interfere with the LP process, cerebrospinal fluid (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.

Sites / Locations

  • UCLA Neuropsychiatric Institute
  • Rady Children's Hospital - San Diego
  • Rush Medical Center
  • Mayo Clinic - Rochester
  • Columbia University Medical Center
  • Carolina Institute for Development Disabilities University of North Carolina/School of Medicine
  • Baylor College of Med; Texas Child Hosp; Pediactric Dept
  • Ospedale Pediatrico Bambino Gesù; Dip. Neuroscienze e Neuroriabilitazione
  • Erasmus MC / location Sophia Kinderziekenhuis
  • Hospital Sant Joan De Deu
  • Corporacio Sanitaria Parc Tauli
  • Hospital Universitario Virgen del Rocío

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm 17

Arm 18

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

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

Cohort EA1 RO7248824

Cohort EA2 RO7248824

Cohort EA3 RO7248824

Cohort EA4 RO7248824

Cohort EB1 RO7248824

Cohort EB2 RO7248824

Cohort EB3 RO7248824

Cohort EB4 RO7248824

Arm Description

Participants 5-12 Years

Participants 5-12 Years

Participants 5-12 Years

Participants 5-12 Years

Participants 5-12 Years

Participants 1-4 Years

Participants 1-4 Years

Participants 1-4 Years

Participants 1-4 Years

Participants 1-4 Years

New participants (age 5-12) enrolling directly in the LTE part

Participants continuing from MAD cohorts A1 and A2

Participants continuing from MAD cohorts A3 and A4

Participants continuing from MAD Cohort A5

New participants (age 1-4) enrolling directly into the LTE

Participants continuing from MAD cohorts B1 and B2

Participants continuing from MAD cohorts B3 and B4

Participants continuing from MAD Cohort B5

Outcomes

Primary Outcome Measures

Frequency And Severity Of Adverse Events
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.
Frequency And Severity Of Serious Adverse Events
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.
Number of Participants Discontinued Treatment due to Adverse Events
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.
Frequency Of Abnormal Laboratory Findings (Blood And Cerebrospinal Fluid [CSF])
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.
Frequency Of Abnormal Vital Signs
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.
Frequency Of Abnormal ECG Values
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 Temperature 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.
Mean Changes From Baseline in Systolic Blood Pressure 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.
Mean Changes From Baseline In Diastolic Blood Pressure 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.
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.
Mean Changes From Baseline In Respiratory Rate 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.

Secondary Outcome Measures

Time to Maximum Concentration (Tmax) for RO7248824
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.
Maximum Plasma Concentration Observed (Cmax) for RO7248824
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.
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 (D365) or early withdrawal. LTE part: From the baseline LTE visit to final LTE visit (D1092) or early withdrawal.
AUC From Time 0 To Infinity (AUCinf) for RO7248824
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.

Full Information

First Posted
June 9, 2020
Last Updated
August 4, 2023
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT04428281
Brief Title
A Study To Investigate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of RO7248824 In Participants With Angelman Syndrome
Official Title
An Open-Label, Multicenter Study To Investigate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of RO7248824 In Participants With Angelman Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 19, 2020 (Actual)
Primary Completion Date
August 3, 2024 (Anticipated)
Study Completion Date
August 3, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a Phase I, multicenter, non-randomized, adaptive, open label, multiple ascending, intra-participant, dose-escalation study with an LTE part. The objective of the study is to investigate the safety, tolerability, PK and PD of RO7248824 in participants administered IT 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 A4 (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-A4 preceding and gating the linked cohort B1-B5 (e.g., A1 precedes B1).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Angelman Syndrome
Keywords
RO7248824; Angelman; ASO; LNA; Angelman syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Non-randomized, adaptive, open label, multiple ascending, intra-participant, dose-escalation study
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
74 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort A1 RO7248824
Arm Type
Experimental
Arm Description
Participants 5-12 Years
Arm Title
Cohort A2 RO7248824
Arm Type
Experimental
Arm Description
Participants 5-12 Years
Arm Title
Cohort A3 RO7248824
Arm Type
Experimental
Arm Description
Participants 5-12 Years
Arm Title
Cohort A4 RO7248824
Arm Type
Experimental
Arm Description
Participants 5-12 Years
Arm Title
Cohort A5 RO7248824
Arm Type
Experimental
Arm Description
Participants 5-12 Years
Arm Title
Cohort B1 RO7248824
Arm Type
Experimental
Arm Description
Participants 1-4 Years
Arm Title
Cohort B2 RO7248824
Arm Type
Experimental
Arm Description
Participants 1-4 Years
Arm Title
Cohort B3 RO7248824
Arm Type
Experimental
Arm Description
Participants 1-4 Years
Arm Title
Cohort B4 RO7248824
Arm Type
Experimental
Arm Description
Participants 1-4 Years
Arm Title
Cohort B5 RO7248824
Arm Type
Experimental
Arm Description
Participants 1-4 Years
Arm Title
Cohort EA1 RO7248824
Arm Type
Experimental
Arm Description
New participants (age 5-12) enrolling directly in the LTE part
Arm Title
Cohort EA2 RO7248824
Arm Type
Experimental
Arm Description
Participants continuing from MAD cohorts A1 and A2
Arm Title
Cohort EA3 RO7248824
Arm Type
Experimental
Arm Description
Participants continuing from MAD cohorts A3 and A4
Arm Title
Cohort EA4 RO7248824
Arm Type
Experimental
Arm Description
Participants continuing from MAD Cohort A5
Arm Title
Cohort EB1 RO7248824
Arm Type
Experimental
Arm Description
New participants (age 1-4) enrolling directly into the LTE
Arm Title
Cohort EB2 RO7248824
Arm Type
Experimental
Arm Description
Participants continuing from MAD cohorts B1 and B2
Arm Title
Cohort EB3 RO7248824
Arm Type
Experimental
Arm Description
Participants continuing from MAD cohorts B3 and B4
Arm Title
Cohort EB4 RO7248824
Arm Type
Experimental
Arm Description
Participants continuing from MAD Cohort B5
Intervention Type
Drug
Intervention Name(s)
RO7248824
Intervention Description
In the Multiple Ascending Dose 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 Long Term Extension part RO7248824 will be administered up to 10 doses as IT injection of selected dose levels with a minimum of approximately 16 weeks between each dose administration.
Primary Outcome Measure Information:
Title
Frequency And Severity Of Adverse Events
Description
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.
Time Frame
Baseline to last visit or early withdrawal
Title
Frequency And Severity Of Serious Adverse Events
Description
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.
Time Frame
Baseline to last visit or early withdrawal
Title
Number of Participants Discontinued Treatment due to Adverse Events
Description
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.
Time Frame
Baseline to last visit or early withdrawal
Title
Frequency Of Abnormal Laboratory Findings (Blood And Cerebrospinal Fluid [CSF])
Description
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.
Time Frame
Baseline to last visit or early withdrawal
Title
Frequency Of Abnormal Vital Signs
Description
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.
Time Frame
Baseline to last visit or early withdrawal
Title
Frequency Of Abnormal ECG Values
Description
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.
Time Frame
Baseline to last visit or early withdrawal
Title
Mean Changes From Baseline in Temperature Over Time
Description
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.
Time Frame
Baseline to last visit or early withdrawal
Title
Mean Changes From Baseline in Systolic Blood Pressure Over Time
Description
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.
Time Frame
Baseline to last visit or early withdrawal
Title
Mean Changes From Baseline In Diastolic Blood Pressure Over Time
Description
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.
Time Frame
Baseline to last visit or early withdrawal
Title
Mean Changes From Baseline In Heartrate Over Time
Description
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.
Time Frame
Baseline to last visit or early withdrawal
Title
Mean Changes From Baseline In Respiratory Rate Over Time
Description
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.
Time Frame
Baseline to last visit or early withdrawal
Secondary Outcome Measure Information:
Title
Time to Maximum Concentration (Tmax) for RO7248824
Description
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.
Time Frame
Baseline to last visit or early withdrawal
Title
Maximum Plasma Concentration Observed (Cmax) for RO7248824
Description
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.
Time Frame
Baseline to last visit or early withdrawal
Title
AUC From Time 0 To Time Of Last Sampling Point Or Last Quantifiable Sample, Whichever Comes First (AUC last) for RO7248824
Description
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.
Time Frame
Baseline to last visit or early withdrawal
Title
AUC From Time 0 To Infinity (AUCinf) for RO7248824
Description
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.
Time Frame
Baseline to last visit or early withdrawal

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 LP and IT injection, under sedation or anesthesia if needed and as determined appropriate by the Investigator. 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 UBE3A mutation of the maternal allele or deletion on the maternally inherited chromosome 15q11q13 that includes the UBE3A gene and is less than 7 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. Exclusion Criteria: 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: UBE3A missense mutation of maternal allele 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. Medical history and concurrent disease Clinically relevant hematological, hepatic, cardiac or renal disease or event, in the judgement of the investigator. Pre-existing abnormal hepatic, renal or hematology lab tests must be discussed with the Sponsor Medical Monitor. 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. A medical history of brain or spinal disease that would interfere with the LP process, cerebrospinal fluid (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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
UCLA Neuropsychiatric Institute
City
Los Angeles
State/Province
California
ZIP/Postal Code
90024
Country
United States
Facility Name
Rady Children's Hospital - San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Rush Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Mayo Clinic - Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Carolina Institute for Development Disabilities University of North Carolina/School of Medicine
City
Carrboro
State/Province
North Carolina
ZIP/Postal Code
27510
Country
United States
Facility Name
Baylor College of Med; Texas Child Hosp; Pediactric Dept
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Ospedale Pediatrico Bambino Gesù; Dip. Neuroscienze e Neuroriabilitazione
City
Roma
State/Province
Lazio
ZIP/Postal Code
00165
Country
Italy
Facility Name
Erasmus MC / location Sophia Kinderziekenhuis
City
Rotterdam
ZIP/Postal Code
3015 GJ
Country
Netherlands
Facility Name
Hospital Sant Joan De Deu
City
Esplugues De Llobregas
State/Province
Barcelona
ZIP/Postal Code
08950
Country
Spain
Facility Name
Corporacio Sanitaria Parc Tauli
City
Sabadell
State/Province
Barcelona
ZIP/Postal Code
08208
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocío
City
Sevilla
ZIP/Postal Code
41013
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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).

Learn more about this trial

A Study To Investigate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of RO7248824 In Participants With Angelman Syndrome

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