ClinicalTrials.gg
Sign In
CompletedNCT03342053Updated Mar 24, 2022Results posted

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7234292 (ISIS 443139) in Huntington's Disease Patients Who Participated in Prior Investigational Studies of RO7234292 (ISIS 443139)

A Phase 2 interventional study of RO7234292 (RG6042) in Huntington's Disease, sponsored by Hoffmann-La Roche. Completed at 9 sites in 3 countries. Open to participants aged 25 Years and older. Per ClinicalTrials.gov, last updated 2022-03-24.

Sponsored by Hoffmann-La Roche · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
46
Allocation
Randomized
Ages
25 Years and older
Sex
All
01

Study summary

This study will test the safety, tolerability, pharmacokinetics and pharmacodynamics of RO7234292 administered intrathecally to adult patients with Huntington's Disease.

02

Conditions studied

  • Huntington's Disease

Browse trials for

03

In context

Huntington Disease

293 studies on the registry are indexed under Huntington Disease; 54 are open to participants now.

This study's enrollment of 46 is above the median of 40 across 207 interventional studies indexed under Huntington Disease.

Browse Huntington Disease studies →

Lead sponsor

Hoffmann-La Roche is the lead sponsor of 2,101 studies on the registry; 87 are open to participants now.

Of its 330 completed or terminated interventional studies of FDA-regulated products, 248 (75%) have results posted.

Browse Hoffmann-La Roche studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
25 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Key Inclusion Criteria:

  • Must have completed dosing in ISIS 443139-CS1

Key Exclusion Criteria:

  • Any new condition or worsening of existing condition that could make the patient unsuitable for participation or interfere with the patient participating in and/or completing the study
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
46 participants (actual)

Study arms

  • Experimental
    RO7234292 Monthly

    RO7234292 is administered every 28 days intrathecally for 14 months.

    Drug: RO7234292 (RG6042)

  • Experimental
    RO7234292 Bimonthly

    RO7234292 is administered every 56 days intrathecally for 14 months following 2 monthly doses to serve as a loading dose.

    Drug: RO7234292 (RG6042)

Interventions

06

What researchers measure

Primary outcomes

  1. Percentage of Participants With Adverse Events

    Adverse Events include Adverse Events that started at or after Date/Time of First Exposure to Treatment and procedure-related Adverse Events occurring before the start of treatment.

    Time frame: From baseline up to 18 months

Secondary outcomes

  1. RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis)

    Time frame: From baseline to Day 421

  2. CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline

    The results of the planned analysis related to mHTT protein levels in CSF are reported

    Time frame: From Baseline to Day 421

  3. Mean Percentage Change in Ventricular Volume Boundary Shift Integral From Baseline to 15 Months

    Time frame: Baseline up to 15 months

  4. Mean Percentage Change in Caudate Volume Boundary Shift Integral From Baseline to 15 Months

    Time frame: Baseline up to 15 months

  5. Mean Percentage Change in Whole Brain Volume Boundary Shift Integral From Baseline to 15 Months

    Time frame: Baseline up to 15 months

  6. EEG Parameters: Mean Change From Baseline to 15 Months in Absolute Power [8-12Hz]

    Time frame: Baseline to 15 Months

  7. Mean Change From Baseline in Huntington's Disease Cognitive Assessment Battery Composite Score

    HD Cognitive Assessment Battery (HD-CAB) was developed to assess cognitive dysfunction in late premanifest and early manifest HD patients. HD-CAB combines scores from six cognitive tests: SDMT, Self-Paced Tapping, Emotional Recognition, CANTAB One Touch Stocking, Hopkins Verbal Learning Test - Revised, and Trail-Making Test. A multi-component score is derived by transforming the subject's score on each cognitive test to a z-score. Using z-scores permits the combination of test scores with different scales. Unlike other measures that use an external reference population to create z-scores, HD-CAB uses the baseline data of the study. Individually, for each of the six cognitive tests, the study baseline mean is subtracted from the subject's score, and this value is divided by the study baseline standard deviation. The six z-scores are averaged to produce the HD-CAB score. A positive change from baseline indicates improvement in cognitive function; a negative change indicates worsening.

    Time frame: Baseline to 15 Months

07

Results

Posted Jan 19, 2021

Participant flow

Participant eligibility for the study was determined within 4 weeks prior to participant entry into the Treatment Period.

Participant flow — Overall Study
MilestoneRO7234292 MonthlyRO7234292 Bimonthly
Started2323
Completed2122
Not completed21
Withdrew: Adverse event20
Withdrew: Withdrawal by subject01

Outcome measures

PrimaryPercentage of Participants With Adverse Events

Adverse Events include Adverse Events that started at or after Date/Time of First Exposure to Treatment and procedure-related Adverse Events occurring before the start of treatment.

Time frame:
From baseline up to 18 months
Reported as:
Number · Percentage of participants
Percentage of Participants With Adverse Events
Percentage of participantsRO7234292 MonthlyRO7234292 Bimonthly
Percentage of Participants With Adverse Events10095.7
SecondaryRO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis)
Time frame:
From baseline to Day 421
Reported as:
Geometric mean · ng/mL
RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis)
ng/mLRO7234292 MonthlyRO7234292 Bimonthly
Day 292.59 (1.31 to 12.7)2.52 (0.817 to 7.85)
Day 573.47 (1.43 to 19.2)—
Day 853.70 (1.38 to 7.34)1.39 (0.164 to 5.74)
Day 1133.97 (1.96 to 16.4)—
Day 1414.57 (1.72 to 13)1.35 (0.396 to 3.69)
Day 1694.47 (2.04 to 12.7)—
Day 1974.58 (1.74 to 8.61)1.26 (0.281 to 3.37)
Day 2255.21 (1.63 to 14.3)—
Day 2534.96 (1.56 to 11.8)1.45 (0.417 to 3.76)
Day 2814.96 (1.30 to 12.4)—
Day 3095.53 (1.74 to 11.6)1.35 (0.195 to 2.77)
Day 3375.12 (2.17 to 10.5)—
Day 3654.50 (1.18 to 13.9)1.45 (0.507 to 2.95)
Day 3933.10 (0.220 to 9.83)—
Day 4213.01 (0.239 to 9.54)1.34 (0.325 to 2.45)
SecondaryCSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline

The results of the planned analysis related to mHTT protein levels in CSF are reported

Time frame:
From Baseline to Day 421
Reported as:
Geometric mean · Log (10) fmol/L
CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline
Log (10) fmol/LRO7234292 MonthlyRO7234292 Bimonthly
Day 29-27.95 (-38.37 to -15.76)-21.84 (-33.22 to -8.52)
Day 57-26.90 (-40.95 to -9.50)10.11 (-41.68 to 107.88)
Day 85-50.30 (-59.00 to -39.75)-32.63 (-44.31 to -18.50)
Day 113-49.11 (-58.77 to -37.18)—
Day 141-54.02 (-61.05 to -45.72)-41.76 (-50.59 to -31.35)
Day 169-42.33 (-53.66 to -28.23)—
Day 197-40.79 (-52.59 to -26.05)-36.48 (-48.99 to -20.89)
Day 225-47.01 (-58.69 to -32.02)—
Day 253-43.63 (-55.39 to -28.77)-41.06 (-53.19 to -25.78)
Day 281-40.29 (-58.63 to -13.80)—
Day 309-36.67 (-50.11 to -19.60)-40.82 (-52.37 to -26.46)
Day 337-42.71 (-58.93 to -20.07)—
Day 365-49.55 (-62.02 to -32.98)-55.07 (-65.46 to -41.57)
Day 393-41.55 (-59.46 to -15.74)—
Day 421-45.45 (-56.21 to -32.03)-41.51 (-52.22 to -28.39)
SecondaryMean Percentage Change in Ventricular Volume Boundary Shift Integral From Baseline to 15 Months
Time frame:
Baseline up to 15 months
Reported as:
Mean · Percentage change
Mean Percentage Change in Ventricular Volume Boundary Shift Integral From Baseline to 15 Months
Percentage changeRO7234292 MonthlyRO7234292 Bimonthly
Mean Percentage Change in Ventricular Volume Boundary Shift Integral From Baseline to 15 Months46.09 ± 32.1418.77 ± 10.36
SecondaryMean Percentage Change in Caudate Volume Boundary Shift Integral From Baseline to 15 Months
Time frame:
Baseline up to 15 months
Reported as:
Mean · Percentage change
Mean Percentage Change in Caudate Volume Boundary Shift Integral From Baseline to 15 Months
Percentage changeRO7234292 MonthlyRO7234292 Bimonthly
Mean Percentage Change in Caudate Volume Boundary Shift Integral From Baseline to 15 Months8.64 ± 6.265.67 ± 2.22
SecondaryMean Percentage Change in Whole Brain Volume Boundary Shift Integral From Baseline to 15 Months
Time frame:
Baseline up to 15 months
Reported as:
Mean · Percentage change
Mean Percentage Change in Whole Brain Volume Boundary Shift Integral From Baseline to 15 Months
Percentage changeRO7234292 MonthlyRO7234292 Bimonthly
Mean Percentage Change in Whole Brain Volume Boundary Shift Integral From Baseline to 15 Months1.63 ± 1.410.89 ± 0.92
SecondaryEEG Parameters: Mean Change From Baseline to 15 Months in Absolute Power [8-12Hz]
Time frame:
Baseline to 15 Months
Reported as:
Mean · log10(mircrovolts^2)
EEG Parameters: Mean Change From Baseline to 15 Months in Absolute Power [8-12Hz]
log10(mircrovolts^2)RO7234292 MonthlyRO7234292 Bimonthly
EEG Parameters: Mean Change From Baseline to 15 Months in Absolute Power [8-12Hz]0.11 ± 0.180.02 ± 0.21
SecondaryMean Change From Baseline in Huntington's Disease Cognitive Assessment Battery Composite Score

HD Cognitive Assessment Battery (HD-CAB) was developed to assess cognitive dysfunction in late premanifest and early manifest HD patients. HD-CAB combines scores from six cognitive tests: SDMT, Self-Paced Tapping, Emotional Recognition, CANTAB One Touch Stocking, Hopkins Verbal Learning Test - Revised, and Trail-Making Test. A multi-component score is derived by transforming the subject's score on each cognitive test to a z-score. Using z-scores permits the combination of test scores with different scales. Unlike other measures that use an external reference population to create z-scores, HD-CAB uses the baseline data of the study. Individually, for each of the six cognitive tests, the study baseline mean is subtracted from the subject's score, and this value is divided by the study baseline standard deviation. The six z-scores are averaged to produce the HD-CAB score. A positive change from baseline indicates improvement in cognitive function; a negative change indicates worsening.

Time frame:
Baseline to 15 Months
Reported as:
Mean · z-score
Mean Change From Baseline in Huntington's Disease Cognitive Assessment Battery Composite Score
z-scoreRO7234292 MonthlyRO7234292 Bimonthly
Mean Change From Baseline in Huntington's Disease Cognitive Assessment Battery Composite Score-0.33 ± 0.27-0.15 ± 0.23

Adverse events

Collected over From baseline to up to 18 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
RO7234292 Monthly1/23 (4.3%)4/23 (17.4%)22/23 (95.7%)
RO7234292 Bimonthly0/23 (0%)3/23 (13%)22/23 (95.7%)
Most frequent serious events
Showing 10 of 19
Most frequent serious events
EventRO7234292 MonthlyRO7234292 Bimonthly
FallInjury, poisoning and procedural complications0/231/23
Skin lacerationInjury, poisoning and procedural complications0/231/23
MyelitisInfections and infestations1/230/23
Cervical vertebral fractureInjury, poisoning and procedural complications0/231/23
Chest injuryInjury, poisoning and procedural complications1/230/23
ConcussionInjury, poisoning and procedural complications0/231/23
Meningitis chemicalInjury, poisoning and procedural complications1/230/23
Rib fractureInjury, poisoning and procedural complications1/230/23
Spinal column injuryInjury, poisoning and procedural complications0/231/23
Thoracic vertebral fractureInjury, poisoning and procedural complications1/230/23
Most frequent other events
Showing 10 of 51
Most frequent other events
EventRO7234292 MonthlyRO7234292 Bimonthly
FallInjury, poisoning and procedural complications18/2312/23
Procedural painInjury, poisoning and procedural complications7/2312/23
NasopharyngitisInfections and infestations9/2310/23
Skin abrasionInjury, poisoning and procedural complications7/234/23
Gait disturbanceGeneral disorders6/230/23
ContusionInjury, poisoning and procedural complications6/235/23
HeadacheNervous system disorders6/234/23
DiarrhoeaGastrointestinal disorders0/235/23
Post lumbar puncture syndromeInjury, poisoning and procedural complications4/235/23
Injection site painGeneral disorders2/234/23

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)RO7234292 MonthlyRO7234292 BimonthlyTotal
<=18 years000
Between 18 and 65 years232043
>=65 years033
Age, Continuous
Age, Continuous(Years)RO7234292 MonthlyRO7234292 BimonthlyTotal
Mean47.7 ± 9.349.5 ± 11.348.6 ± 10.3
Sex: Female, Male
Sex: Female, Male(Participants)RO7234292 MonthlyRO7234292 BimonthlyTotal
Female81018
Male151328
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)RO7234292 MonthlyRO7234292 BimonthlyTotal
Hispanic or Latino000
Not Hispanic or Latino232346
Unknown or Not Reported000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)RO7234292 MonthlyRO7234292 BimonthlyTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American000
White222345
More than one race000
Other101
08

Study locations

9 sites
  • The University of British Columbia; The Centre for Huntington Disease
    Vancouver, British Columbia V6T 2B5, Canada
  • Charité - Universitätsmedizin Berlin, Campus Charité Mitte; Klinik für Psychiatrie und Psychotherapi
    Berlin, 10117, Germany
  • St. Josef and St. Elisabeth GmbH ; Klinikum Bochum, Zentralapotheke
    Bochum, 44791, Germany
  • Universitaetsklinikum Ulm
    Ulm, 89081, Germany
  • NIHR Welcome Trust Birmingham CRF - University Hospitals Birmingham; Department of Neuropsychiatry
    Birmingham, B15 2FG, United Kingdom
  • University of Cambridge - John van Geest Centre for Brain Repair
    Cambridge, CB2 0PY, United Kingdom
  • Cardiff University School of Medicine; Institute of Psychological Medicine Clinical Neurosciences
    Cardiff, CF24 4HQ, United Kingdom
  • Leonard Wolfson Experimental Neurology Centre
    London, WC1N 3BG, United Kingdom
  • Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine
    Manchester, M13 9WL, United Kingdom
09

References and documents

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Jan 2018 to primary completion in Oct 2019, 21 months.

Results were first posted in Jan 2021, 1 year 3 months after primary completion.

Of 22 phase 2 interventional studies under Huntington Disease, half reached primary completion within 31 months of starting (the median), counting those still running; a quarter within 21 and three quarters within 40. This study's 21 months is below that.

How these figures are worked out, and which studies are left out of them.

Registered
Oct 31, 2017
First posted
Nov 14, 2017
StartActual
Jan 2, 2018
Primary completionActual
Oct 8, 2019
CompletionActual
Oct 8, 2019
Results first posted
Jan 19, 2021
Last update
Mar 24, 2022
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Mar 24, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03342053
Lead sponsor
Hoffmann-La Roche
Responsible party
Sponsor
First posted
Nov 14, 2017
Start date
Jan 2, 2018
Primary completion
Oct 8, 2019
Completion
Oct 8, 2019
Results posted
Jan 19, 2021
Last update
Mar 24, 2022

Study contacts

Clinical Trials
study director · Hoffmann-La Roche

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2022. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Tominersen

Other studies in this condition

Huntington Disease →

Other studies from this sponsor

Hoffmann-La Roche →

Start the discussion