A Study to Investigate the Pharmacokinetics (PK) and Safety and to Provide Proof of Mechanism of Alogabat in Children and Adolescents Aged 5-17 Years With Angelman Syndrome (AS) With Deletion Genotype.

NCT ID: NCT05630066

Last Updated: 2025-12-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-27
• Study Completion Date: 2025-12-02

Brief Summary

This is a two-part, Phase IIa, multicenter, 12-week, open-label study. Up to 56 participants with deletion AS aged 5-17 years (inclusive) will be enrolled in the study.

Detailed Description

The study will have Part 1-dose confirmations and Part 2 with dose levels to be decided based on the cumulative PK, electroencephalography (EEG), and safety data emerging from Part 1.

The dose levels for the first cohort of Part 2 will be decided based on the cumulative PK, EEG, and safety data emerging from Part 1.

Part 2 will explore the change in EEG beta-band power relative to baseline at Week 2, Week 4 (i.e., approximately 2 weeks after the start of the Dose B), and at the end of the 12-week treatment period after daily administration of alogabat.

Conditions

Angelman Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1 Adult Alogabat Dose (Age 15-17)

In Part 1 of the study participants will receive alogabat once a day (QD).

Group Type: EXPERIMENTAL

Alogabat

Intervention Type: DRUG

Alogabat will be administered QD with dose depending on cohort and age of the participant.

Part 1 Age-adjusted Dose (Age 10-14)

In Part 1 of the study, participants will receive age-adjusted QD doses of alogabat.

Group Type: EXPERIMENTAL

Alogabat

Intervention Type: DRUG

Alogabat will be administered QD with dose depending on cohort and age of the participant.

Part 1 Age-adjusted Dose (Age 5-9)

In Part 1 of the study, participants will receive age-adjusted QD doses of alogabat.

Group Type: EXPERIMENTAL

Alogabat

Intervention Type: DRUG

Alogabat will be administered QD with dose depending on cohort and age of the participant.

Part 2 Cohort 1

In Part 2 of the study, the dosing will depend upon the results of Part 1 with two different dose levels per cohort. Doses can be age-adjusted.

Group Type: EXPERIMENTAL

Alogabat

Intervention Type: DRUG

Alogabat will be administered QD with dose depending on cohort and age of the participant.

Part 2 Cohort 2

In Part 2 of the study, the dosing will depend upon the interim results with two different dose levels per cohort. Doses can be age-adjusted.

Group Type: EXPERIMENTAL

Alogabat

Intervention Type: DRUG

Alogabat will be administered QD with dose depending on cohort and age of the participant.

Part 1 Optional Cohort

If dose adjustments (e.g., increase or decrease in dose) are required, particularly due to uncertainty of the clearance estimates (e.g., due to high variability) or over-/underprediction of the pediatric clearance versus adult clearance, additional participants may be recruited in any of the of the 3 age-groups in order to confirm the exposure equivalence. A total of two optional cohorts may be utilized in this study, allocated to Part 1 and/or Part 2.

Group Type: EXPERIMENTAL

Alogabat

Intervention Type: DRUG

Alogabat will be administered QD with dose depending on cohort and age of the participant.

Part 2 Optional Cohort

In Part 2 of the study, the dosing will depend upon the interim results with two different dose levels per cohort. Doses can be age-adjusted.

Group Type: EXPERIMENTAL

Alogabat

Intervention Type: DRUG

Alogabat will be administered QD with dose depending on cohort and age of the participant.

Interventions

Alogabat

Alogabat will be administered QD with dose depending on cohort and age of the participant.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Clinical diagnosis of AS and a genetic subtype of deletion on chromosome 15q11q13 confirmed by a historical molecular diagnosis
• The participant's general health status, in the context of the disease under study, allows them to participate in a clinical trial in the opinion of the investigator
• 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
• Female participants:

A female participant is eligible to participate if she is not pregnant, not breastfeeding, and non-childbearing or remain abstinent and/or Hormonal contraceptive methods must be supplemented

-Male participants: Male contraception is not required in this study because of the minimal seminal dose transmitted through sexual intercourse

Exclusion Criteria

• A molecular diagnosis of AS with genotypic classification of any type besides the molecular diagnosis as specified in Inclusion Criterion
• Concurrent cardiovascular disease considered not well controlled by drug treatment, including participants with clinically significant hypertension, bradycardia and arrhythmias, myocardial infarction (MI) within 12 months of screening or uncompensated heart failure
• Confirmed clinically significant abnormality on 12-lead electrocardiogram (ECG), including:
• a QT corrected for heart rate using the Fridericia's correction factor (QTcF) of >/= 450 ms (based on the average of 3 consecutive measurements) for participants older than 10 years old
• a QT corrected for heart rate using Bazett's formula (QTcB) of >/= 450 ms (based on the average of 3 consecutive measurements) for participants up to, and including, the age of 10 years old
• Congenital heart diseases not treated and congenital QT corrected for heart rate (QTc) prolongation or family history of Long QT Syndrome
• Medical history of malignancy if not considered cured or if occurred within the last 5 years with the exception of fully excised non-melanoma skin cancers or in-situ carcinoma of the cervix that has been successfully treated
• Concomitant disease, condition, or treatment that would either interfere with the conduct of the study or pose an unacceptable risk to the participant in the opinion of the investigator
• Known active or uncontrolled bacterial, viral, or other infection (excluding fungal infections of nail beds) or any major episode of infection or hospitalization (relating to the completion of the course of antibiotics) within 6 weeks prior to the start of drug administration. Rescreening is allowed once the infection is cured and if the rescreening criteria are met
• 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)
• Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study. Rescreening is allowed not earlier than 12 weeks after the surgery and if the rescreening criteria are met.
• Use of prohibited medications within 6 weeks or 5 half-lives (t1/2) prior to start of study medication on Day 1 (whichever is longer)
• Clinically significant loss of blood within 3 months prior to screening defined by participant age and weight per recommendations from Duke University (2012)
• Any prior or current treatment with an investigational study drug within 6 weeks or 5 times the t1/2 of the investigational molecule (whichever is longer) prior to baseline or prior or current use of an investigational medical device within 6 weeks prior to baseline or if the device is still active. Concurrent or planned concurrent participation in any clinical study (including observational and non-interventional studies) without approval of the Investigator.
• Previous participation in a cellular therapy, gene therapy, or gene editing clinical study
• Clinically significant vital sign or ECG abnormalities at Screening
• Confirmed clinically significant abnormality in hematological, chemistry or coagulation laboratory parameters
• Uncorrected hypokalemia or hypomagnesaemia
• Positive test result at screening for hepatitis B surface antigen (HBsAg), HCV (untreated), or HIV-1/2. Participants with HCV who have been successfully treated and who test negative for HCV ribonucleic acid (HCV RNA) may be considered eligible for entry into the study

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Dr. Von Haunersches Kinderspital

München, , Germany

Ospedale Pediatrico Bambino Gesù

Rome, Lazio, Italy

IRCCS Istituto G. Gaslini

Genoa, Liguria, Italy

IRCCS Eugenio Medea

Conegliano Veneto (TV), Veneto, Italy

Groupe Hospitalier Necker Enfants Malades

Paris, , France

Rush Medical Center

Chicago, Illinois, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Columbia University Medical Center

New York, New York, United States

Carolina Institute for Development DisabilitiesUniversity of North Carolina/School of Medicine

Carrboro, North Carolina, United States

Vanderbilt Children's Hospital

Nashville, Tennessee, United States

Multicare Institute for Research and Innovation

Tacoma, Washington, United States

Queensland Children?s Hospital

South Brisbane, Queensland, Australia

CHRU de Brest

Brest, , France

CHU Dijon Bourgogne Hôpital François Mitterand

Dijon, , France

Hopital la Timone Enfants

Marseille, , France

Hospital Sant Joan de Deu

Esplugues de Llobregat · Barcelona, Barcelona, Spain

Corporacio Sanitaria Parc Tauli

Sabadell, Barcelona, Spain

Hospital Universitario de Navarra;Unidad de Neuropediatría

Pamploa, Navarre, Spain

Hospital Universitario Puerta De Hierro Majadahonda

Madrid, , Spain

Countries

United States; Australia; France; Germany; Italy; Spain

Other Identifiers

2022-501844-14-00

Identifier Type: CTIS

Identifier Source: secondary_id

BP41315

Identifier Type: -

Identifier Source: org_study_id