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.

NCT05630066 | Completed Phase 2 FDA Drug

• 2 other identifiers: BP413152022-501844-14-00
• Study Type: interventional
• Target: 48
• Locations: 6 countries
• Sites: 19

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.

Conditions

Angelman Syndrome

Outcome Measures

Primary Outcomes (3)

• Part 1: Age-group Based Ratio of Plasma PK Parameter, Area Under the Concentration-time Curve (AUC)

  Age-group based ratio of plasma PK parameters in pediatric participants with AS versus data collected from adult healthy volunteers and participants with autism spectrum disorder (ASD) (AUC)

  Up to 12 Weeks

• Part 1: Age-group Based Ratio of Plasma PK Parameter, Apparent Clearance (CL/F)

  Age-group based ratio of plasma PK parameters in pediatric participants with AS versus data collected from adult healthy volunteers and participants with ASD (CL/F)

  Up to 12 Weeks

• Part 2: Change From Baseline to Week 2, 4, and 12 in Resting State EEG Power in the Beta Band

  Week 2, 4, and 12

Secondary Outcomes (6)

• Parts 1 and 2: Plasma PK Parameter of Alogabat, Maximum Concentration (Cmax)

  Up to 12 Weeks

• Parts 1 and 2: Plasma PK Parameter of Alogabat, AUC

  Up to 12 Weeks

• Parts 1 and 2: Plasma PK Parameter of Alogabat, CL/F

  Up to 12 Weeks

• Parts 1 and 2: Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to 18 Weeks

• Parts 1 and 2: Incidence of Treatment Discontinuations due to AEs

  Up to 18 Weeks

Study Arms (7)

Part 1 Adult Alogabat Dose (Age 15-17)

EXPERIMENTAL

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

Drug: Alogabat

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

EXPERIMENTAL

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

Drug: Alogabat

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

EXPERIMENTAL

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

Drug: Alogabat

Part 2 Cohort 1

EXPERIMENTAL

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.

Drug: Alogabat

Part 2 Cohort 2

EXPERIMENTAL

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.

Drug: Alogabat

Part 1 Optional Cohort

EXPERIMENTAL

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.

Drug: Alogabat

Part 2 Optional Cohort

EXPERIMENTAL

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.

Drug: Alogabat

Interventions

Alogabat DRUG

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

Part 1 Adult Alogabat Dose (Age 15-17); Part 1 Age-adjusted Dose (Age 10-14); Part 1 Age-adjusted Dose (Age 5-9); Part 1 Optional Cohort; Part 2 Cohort 1; Part 2 Cohort 2; Part 2 Optional Cohort

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (19)

Rush Medical Center

Chicago, Illinois, 60612, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

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

Carrboro, North Carolina, 27510, United States

Location

Vanderbilt Children's Hospital

Nashville, Tennessee, 37232-9119, United States

Location

Multicare Institute for Research and Innovation

Tacoma, Washington, 98405, United States

Location

Queensland Children?s Hospital

South Brisbane, Queensland, 4101, Australia

Location

CHRU de Brest

Brest, 29609, France

Location

CHU Dijon Bourgogne Hôpital François Mitterand

Dijon, 21000, France

Location

Hopital la Timone Enfants

Marseille, 13005, France

Location

Groupe Hospitalier Necker Enfants Malades

Paris, 75015, France

Location

Dr. Von Haunersches Kinderspital

München, 80337, Germany

Location

Ospedale Pediatrico Bambino Gesù

Rome, Lazio, 00165, Italy

Location

IRCCS Istituto G. Gaslini

Genoa, Liguria, 16147, Italy

Location

IRCCS Eugenio Medea

Conegliano Veneto (TV), Veneto, 31015, Italy

Location

Hospital Sant Joan de Deu

Esplugues de Llobregat · Barcelona, Barcelona, 08950, Spain

Location

Corporacio Sanitaria Parc Tauli

Sabadell, Barcelona, 08208, Spain

Location

Hospital Universitario de Navarra;Unidad de Neuropediatría

Pamploa, Navarre, 31008, Spain

Location

Hospital Universitario Puerta De Hierro Majadahonda

Madrid, 28222, Spain

Location

MeSH Terms

Conditions

Angelman Syndrome

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: There will be up to 7 cohorts. The adolescents aged 15-17 will receive the adult dose. Dosing in Part 1 is pre-specified. Cohorts in Part 1 enroll a specific age range (15-17, 10-14, 5-9), with older cohorts being initiated prior to younger ones. Part 2 features mixed-age cohorts, with age-adjusted doses. Within each Part 2 cohort, two different doses of alogabat may be used: one up to Week 2 (Dose A), and the other from Week 3 to Week 12 (Dose B). Part 2 opens enrolment for ages 10-17 years following analysis of the 2-week data from the Part 1 cohorts aged 15-17 years and 10-14 years. Ages 5-9 years may enroll in Part 2 following analysis of the 2-week data from the Part 1 cohort with participants aged 5-9 years. Part 2 Cohort 2 will open enrollment across ages following the review of Week 2 and Week 4 data in Part 2 Cohort 1. A total of two optional cohorts may be utilized in this study, allocated to Part 1 and/or Part 2.

Study Record Dates

• First Submitted: November 9, 2022
• First Posted: November 29, 2022
• Study Start: July 27, 2023
• Primary Completion: December 2, 2025
• Study Completion: December 2, 2025
• Last Updated: December 4, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

IT (3); FR (4); ES (4); AU (1); DE (1); US (6)