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| ID | Type | Description | Link |
|---|---|---|---|
| 2022-501844-14-00 | EU Trial (CTIS) Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 Adult Alogabat Dose (Age 15-17) | Experimental | In Part 1 of the study participants will receive alogabat once a day (QD). |
|
| Part 1 Age-adjusted Dose (Age 10-14) | Experimental | In Part 1 of the study, participants will receive age-adjusted QD doses of 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. |
|
| 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. |
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| 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. |
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| Part 1 Optional Cohort |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alogabat | Drug | Alogabat will be administered QD with dose depending on cohort and age of the participant. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Parts 1 and 2: Plasma PK Parameter of Alogabat, Maximum Concentration (Cmax) | Plasma PK parameter of alogabat Cmax as derived using a population-pharmacokinetic (popPK) model | Up to 12 Weeks |
| Parts 1 and 2: Plasma PK Parameter of Alogabat, AUC |
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Inclusion Criteria:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rush Medical Center | Chicago | Illinois | 60612 | United States | ||
| Boston Children's Hospital |
For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing
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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.
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| 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. |
|
| 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. |
|
Plasma PK parameter of alogabat AUC as derived using a popPK model
| Up to 12 Weeks |
| Parts 1 and 2: Plasma PK Parameter of Alogabat, CL/F | Plasma PK parameter of alogabat CL/F derived using a popPK model | Up to 12 Weeks |
| Parts 1 and 2: Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Incidence and severity of AEs and SAEs | Up to 18 Weeks |
| Parts 1 and 2: Incidence of Treatment Discontinuations due to AEs | Incidence of treatment discontinuations due to AEs | Up to 18 Weeks |
| Parts 1 and 2: Incidence of Daytime Sleepiness Assessed With the Karolinska Sleepiness Scale (KSS), and Incidence of Sudden Onset of Sleep Assessed With Somnolence Diary | Incidence of daytime sleepiness assessed with the KSS, and incidence of sudden onset of sleep assessed with somnolence diary. | Up to 12 Weeks |
| Boston |
| Massachusetts |
| 02115 |
| United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| Carolina Institute for Development DisabilitiesUniversity of North Carolina/School of Medicine | Carrboro | North Carolina | 27510 | United States |
| Vanderbilt Children's Hospital | Nashville | Tennessee | 37232-9119 | United States |
| Multicare Institute for Research and Innovation | Tacoma | Washington | 98405 | United States |
| Queensland Children?s Hospital | South Brisbane | Queensland | 4101 | Australia |
| CHRU de Brest | Brest | 29609 | France |
| CHU Dijon Bourgogne Hôpital François Mitterand | Dijon | 21000 | France |
| Hopital la Timone Enfants | Marseille | 13005 | France |
| Groupe Hospitalier Necker Enfants Malades | Paris | 75015 | France |
| Dr. Von Haunersches Kinderspital | München | 80337 | Germany |
| Ospedale Pediatrico Bambino Gesù | Rome | Lazio | 00165 | Italy |
| IRCCS Istituto G. Gaslini | Genoa | Liguria | 16147 | Italy |
| IRCCS Eugenio Medea | Conegliano Veneto (TV) | Veneto | 31015 | Italy |
| Hospital Sant Joan de Deu | Esplugues de Llobregat · Barcelona | Barcelona | 08950 | Spain |
| Corporacio Sanitaria Parc Tauli | Sabadell | Barcelona | 08208 | Spain |
| Hospital Universitario de Navarra;Unidad de Neuropediatría | Pamploa | Navarre | 31008 | Spain |
| Hospital Universitario Puerta De Hierro Majadahonda | Madrid | 28222 | Spain |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| May 21, 2026 | Jun 18, 2026 | 43 |
| ID | Term |
|---|---|
| D017204 | Angelman Syndrome |
| ID | Term |
|---|---|
| D009069 | Movement Disorders |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D025063 | Chromosome Disorders |
| D030342 | Genetic Diseases, Inborn |
| D000096803 | Imprinting Disorders |
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