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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05686551




Registration number
NCT05686551
Ethics application status
Date submitted
16/12/2022
Date registered
17/01/2023

Titles & IDs
Public title
GENERATION HD2. A Study to Evaluate the Safety, Biomarkers, and Efficacy of Tominersen Compared With Placebo in Participants With Prodromal and Early Manifest Huntington's Disease.
Scientific title
A Phase II, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study to Evaluate the Safety, Biomarkers, and Efficacy of Tominersen in Individuals With Prodromal and Early Manifest Huntington's Disease
Secondary ID [1] 0 0
Other
Secondary ID [2] 0 0
BN42489
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Huntington Disease 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tominersen 60 mg
Treatment: Drugs - Placebo
Treatment: Drugs - Tominersen 100 mg

Experimental: Tominersen 60 mg -

Placebo comparator: Placebo -

Experimental: Tominersen 100 mg -


Treatment: Drugs: Tominersen 60 mg
60 mg tominersen administered intrathecally every 16 weeks

Treatment: Drugs: Placebo
Matching placebo administered intrathecally every 16 weeks

Treatment: Drugs: Tominersen 100 mg
100 mg tominersen administered intrathecally every 16 weeks
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence and severity of adverse events, with severity determined according to the Adverse Event Severity Grading Scale
Timepoint [1] 0 0
Up to Approximately 24 Months
Primary outcome [2] 0 0
Change from baseline in clinical laboratory results - Cerebrospinal fluid (CSF) White Blood Cell (WBC) (1/uL)
Timepoint [2] 0 0
From Baseline Visit (Day 1), and Months 4, 8, 9, 12, 16
Primary outcome [3] 0 0
Change from baseline in clinical laboratory results Cerebrospinal fluid (CSF) protein (g/L)
Timepoint [3] 0 0
From Baseline Visit (Day 1), and Months 4, 8, 9, 12, 16
Primary outcome [4] 0 0
Change in baseline in structural MRI assessing any new abnormalities including radiographic features consistent with hydrocephalus and other relevant MRI safety findings
Timepoint [4] 0 0
From Baseline, Months 4, 8, 12, 16 and Up to Approximately Month 24
Primary outcome [5] 0 0
Percentage change from baseline in geometric means of CSF mHTT protein levels at Month 9
Timepoint [5] 0 0
Baseline and Month 9
Primary outcome [6] 0 0
Change from baseline in composite Unified Huntington's Disease Rating Scale (cUHDRS) Scores (non-U.S. sites) at 16 months
Timepoint [6] 0 0
Baseline to 16 Months
Primary outcome [7] 0 0
Change from baseline in Total Functional Capacity (TFC) Scores (U.S. sites) at 16 months
Timepoint [7] 0 0
Baseline to 16 Months
Secondary outcome [1] 0 0
Change from baseline in MoCA Scores
Timepoint [1] 0 0
From Baseline, Months 4, 8, 12, 16 and up to approximately Month 24
Secondary outcome [2] 0 0
Percentage of participants with suicidal ideation or behavior as assessed by C-SSRS score at each visit, including detailed focus on any individual cases identified as having severe ideation or behavior during the study conduct
Timepoint [2] 0 0
Up to Approximately 24 Months
Secondary outcome [3] 0 0
Change from baseline at 16 months for the assessments of TFC (non-U.S. sites) Scores
Timepoint [3] 0 0
Baseline to 16 Months
Secondary outcome [4] 0 0
Change from baseline at 16 months for the assessments of cUHDRS (U.S. sites) Scores
Timepoint [4] 0 0
Baseline to 16 Months
Secondary outcome [5] 0 0
Change from baseline at 16 months for the assessments of Symbol Digit Modalities Test (SDMT) Scores
Timepoint [5] 0 0
Baseline to 16 Months
Secondary outcome [6] 0 0
Change from Baseline at 16 Months for the Assessments of Stroop Word Reading (SWR) Scores
Timepoint [6] 0 0
Baseline to 16 Months
Secondary outcome [7] 0 0
Change from baseline at 16 months for the assessments of Total Motor Score (TMS)
Timepoint [7] 0 0
Baseline to 16 Months
Secondary outcome [8] 0 0
Change from baseline in CSF Neurofilament light Chain (NfL) levels at 16 months
Timepoint [8] 0 0
Baseline to 16 Months
Secondary outcome [9] 0 0
Incidence of anti-drug antibodies (ADAs) at specified timepoints relative to the prevalence of ADAs at baseline
Timepoint [9] 0 0
From Baseline, Months 4, 8, 12, 16 and Up to Approximately Month 24
Secondary outcome [10] 0 0
Titers determined if ADAs are identified
Timepoint [10] 0 0
From Baseline, Months 4, 8, 12, 16 and Up to Approximately Month 24

Eligibility
Key inclusion criteria
Key Inclusion Criteria

-Huntington's disease (HD) gene expansion mutation carrier status with a CAP score of 400-500 inclusive

Either:

* Prodromal HD (defined as DCL 2 to 3, Independence Scale (IS) ?70, and ?TFC8); or
* Early manifest HD (defined as DCL 4, Independence Scale (IS) ?70, and ?TFC8);
* Total body weight > 40 kg and a body mass index within the range of 18-32 kg/m2
* Study Companion

Key
Minimum age
25 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

* Current or previous use of an ASO (including small interfering RNA) or any HTT lowering therapy (including tominersen)
* Anti-platelet or anticoagulant therapy within 14 days prior to screening or anticipated use during the study, including, but not limited to, aspirin (unless </= 81 mg/day), clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban, apixaban, and heparin
* History of gene therapy, cell transplantation, or brain surgery
* Hydrocephalus
* Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 5 months after the final dose of study drug
* History of attempted suicide or suicidal ideation with plan (i.e., active suicidal ideation) that required hospital visit and/or change in level of care within 12 months prior to screening

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
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
3/02/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2027
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
WESTMEAD HOSPITAL; Deparment of Neurology - Westmead
Recruitment hospital [2] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [3] 0 0
Royal Melbourne Hospital; Department of Neurology - Parkville
Recruitment hospital [4] 0 0
Perron Institute for Neurological and Translational Science - Nedlands
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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California
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Colorado
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District of Columbia
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Florida
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Illinois
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Iowa
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Maryland
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Massachusetts
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Michigan
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Texas
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Washington
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Argentina
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Buenos Aires
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Argentina
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Caba
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Argentina
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Capital Federal
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Argentina
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Ciudad Autonoma Buenos Aires
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Austria
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Innsbruck
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Canada
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Alberta
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Bochum
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Bonn
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Germany
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Germany
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Lübeck
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Germany
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Taufkirchen
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Germany
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Ulm
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Emilia-Romagna
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Lazio
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Italy
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Christchurch
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Hamilton
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Gda?sk
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Krakow
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Lisboa
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Vizcaya
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Basel
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Gümligen
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Birmingham
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Cambridge
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Chinnor
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Leeds
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London
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United Kingdom
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Southampton

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: BN42489. 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/NCT05686551