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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05630066




Registration number
NCT05630066
Ethics application status
Date submitted
9/11/2022
Date registered
29/11/2022

Titles & IDs
Public title
Study to Investigate the Pharmacokinetics 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.
Scientific title
A Phase IIa Multicenter, Open-Label, 12-Week Study to Investigate the Pharmacokinetics 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
Secondary ID [1] 0 0
2022-501844-14-00
Secondary ID [2] 0 0
BP41315
Universal Trial Number (UTN)
Trial acronym
Aldebaran
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Angelman Syndrome 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Other neurological disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 60 mg QD Alogabat
Treatment: Drugs - 40 mg QD Alogabat
Treatment: Drugs - 7 mg QD Alogabat
Treatment: Drugs - Part 2 Adult Alogabat High Dose (aged 15-17)
Treatment: Drugs - Alogabat
Treatment: Drugs - Alogabat
Treatment: Drugs - Part 2 Optional Cohort

Experimental: Part 1 Adult Alogabat High Dose (aged 15-17) - In Part 1 of the study, participants will receive age-adjusted dose 60 mg QD alogabat

Experimental: Part 1 Age adjusted high dose (age 10-14) - In Part 1 of the study, participants will receive age-adjusted dose 60 mg QD alogabat.

Experimental: Part 1 Age Adjusted Low Dose (age 5-9) - In Part 1 of the study, participants will receive age-adjusted dose 20 mg QD alogabat.

Experimental: Part 2 Cohort 1 - In Part 2 of the study, the dosing will depend upon the results of Part 1, with age-adjusted dose equivalents of up to 100 mg being administered.

Experimental: Part 2 Cohort 2 - In Part 2 of the study, the dosing will depend upon the results of Part 1, with age-adjusted dose equivalents of up to 100 mg being administered.

Experimental: 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.

Experimental: Part 2 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, participants from any of the 3 age-groups may enroll 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.


Treatment: Drugs: 60 mg QD Alogabat
Participants aged 15-17 years or above receiving the adult 60 mg of alogabat dose.

I

Treatment: Drugs: 40 mg QD Alogabat
Participants aged 10-14 years receiving the equivalent of the adult 60 mg alogabat dose.

Treatment: Drugs: 7 mg QD Alogabat
Participants aged 5-9 years receiving the equivalent of the adult 20 mg alogabat dose.

Treatment: Drugs: Part 2 Adult Alogabat High Dose (aged 15-17)
In Part 2 of the study, the dosing will depend upon the results of Part 1, with age-adjusted dose equivalents of up to 100 mg being administered.

Treatment: Drugs: Alogabat
In Part 2 of the study, the dosing will depend upon the results of Part 1, with age-adjusted dose equivalents of up to 100 mg being administered.

Treatment: Drugs: Alogabat
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.

Treatment: Drugs: Part 2 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, participants from any of the 3 age-groups may enroll 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Age-group based ratio of plasma PK parameter, area under the concentration-time curve (AUC)
Timepoint [1] 0 0
Up to 12 Weeks
Primary outcome [2] 0 0
Age-group based ratio of plasma PK parameter, apparent clearance (CL/F)
Timepoint [2] 0 0
Up to 12 Weeks
Primary outcome [3] 0 0
Change from baseline to Week 2, 4, and 12 in resting state EEG power in the beta band
Timepoint [3] 0 0
Week 2, 4, and 12
Secondary outcome [1] 0 0
Plasma pharmacokinetic parameter of alogabat, maximum concentration (Cmax)
Timepoint [1] 0 0
Up to 12 Weeks
Secondary outcome [2] 0 0
Plasma pharmacokinetic parameters of alogabat area under the concentration-time curve (AUC)
Timepoint [2] 0 0
Up to 12 Weeks
Secondary outcome [3] 0 0
Plasma pharmacokinetic parameter of alogabat, apparent clearance (CL/F)
Timepoint [3] 0 0
Up to 12 Weeks
Secondary outcome [4] 0 0
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs).
Timepoint [4] 0 0
Up to 18 Weeks
Secondary outcome [5] 0 0
Incidence of treatment discontinuations due to AEs
Timepoint [5] 0 0
Up to 18 Weeks
Secondary outcome [6] 0 0
Incidence of daytime sleepiness assessed with the Karolinska Sleepiness Scale (KSS), and incidence of sudden onset of sleep assessed with somnolence diary
Timepoint [6] 0 0
Up to 21 Weeks

Eligibility
Key inclusion criteria
* Clinical diagnosis of AS and a genetic subtype of deletion on the maternally inherited chromosome 15q11q13 confirmed by a historical molecular diagnosis. The deletion must include UBE3A, GABRB3, GABRA5, and GABRG3 genes, and be less than 7 Mb in size.
* Body mass index (BMI) below the 97th percentile and above the 3rd percentile for the same age and sex
* 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
Minimum age
5 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 within 12 months of screening or uncompensated heart failure
* Confirmed clinically significant abnormality on 12-lead ECG, including:
* a QTcF of >/= 450 ms (based on the average of 3 consecutive measurements) for participants older than 10 years old
* a 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 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 RNA may be considered eligible for entry into the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/07/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
12/09/2025
Actual
Sample size
Target
56
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA
Recruitment hospital [1] 0 0
Queensland Children?s Hospital - South Brisbane
Recruitment hospital [2] 0 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
5042 - Bedford Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
France
State/province [9] 0 0
Brest
Country [10] 0 0
France
State/province [10] 0 0
Marseille
Country [11] 0 0
France
State/province [11] 0 0
Paris
Country [12] 0 0
Germany
State/province [12] 0 0
München
Country [13] 0 0
Italy
State/province [13] 0 0
Lazio
Country [14] 0 0
Italy
State/province [14] 0 0
Liguria
Country [15] 0 0
Italy
State/province [15] 0 0
Veneto
Country [16] 0 0
Spain
State/province [16] 0 0
Barcelona
Country [17] 0 0
Spain
State/province [17] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: BP41315 https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. Only)
Fax 0 0
Email 0 0
global-roche-genentech-trials@gene.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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/ourmember/roche/). 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).

Supporting document/s available: Study protocol
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05630066