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Trial record 2 of 18 for:    isis AND huntington's

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03342053
Recruitment Status : Completed
First Posted : November 14, 2017
Results First Posted : January 19, 2021
Last Update Posted : March 24, 2022
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Huntington's Disease
Intervention Drug: RO7234292 (RG6042)
Enrollment 46
Recruitment Details Participant eligibility for the study was determined within 4 weeks prior to participant entry into the Treatment Period.
Pre-assignment Details  
Arm/Group Title RO7234292 Monthly RO7234292 Bimonthly
Hide Arm/Group Description RO7234292 was administered intrathecally every 28 days for 14 months. RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
Period Title: Overall Study
Started 23 23
Completed 21 22
Not Completed 2 1
Reason Not Completed
Adverse Event             2             0
Withdrawal by Subject             0             1
Arm/Group Title RO7234292 Monthly RO7234292 Bimonthly Total
Hide Arm/Group Description RO7234292 was administered intrathecally every 28 days for 14 months. RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose. Total of all reporting groups
Overall Number of Baseline Participants 23 23 46
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 23 participants 46 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
23
 100.0%
20
  87.0%
43
  93.5%
>=65 years
0
   0.0%
3
  13.0%
3
   6.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 23 participants 23 participants 46 participants
47.7  (9.3) 49.5  (11.3) 48.6  (10.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 23 participants 46 participants
Female
8
  34.8%
10
  43.5%
18
  39.1%
Male
15
  65.2%
13
  56.5%
28
  60.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 23 participants 46 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
23
 100.0%
23
 100.0%
46
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 23 participants 46 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
22
  95.7%
23
 100.0%
45
  97.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Other
1
   4.3%
0
   0.0%
1
   2.2%
[1]
Measure Analysis Population Description: One participant's race is known, was reported but cannot be classified in Roche database
1.Primary Outcome
Title Percentage of Participants With Adverse Events
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population comprising all participants that were randomized and received at least one dose of RO7234292.
Arm/Group Title RO7234292 Monthly RO7234292 Bimonthly
Hide Arm/Group Description:
RO7234292 was administered intrathecally every 28 days for 14 months.
RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
Overall Number of Participants Analyzed 23 23
Measure Type: Number
Unit of Measure: Percentage of participants
100 95.7
2.Secondary Outcome
Title RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis)
Hide Description [Not Specified]
Time Frame From baseline to Day 421
Hide Outcome Measure Data
Hide Analysis Population Description
CSF Trough Concentrations were reported following study drug administration. Data for Bi-monthly arm was not collected on days 57, 113, 169, 225, 281, 337, 393. Here "Number Analyzed" represents number of participants from whom samples were collected and analyzed.
Arm/Group Title RO7234292 Monthly RO7234292 Bimonthly
Hide Arm/Group Description:
RO7234292 was administered intrathecally every 28 days for 14 months.
RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
Overall Number of Participants Analyzed 23 23
Geometric Mean (Full Range)
Unit of Measure: ng/mL
Day 29 Number Analyzed 22 participants 21 participants
2.59
(1.31 to 12.7)
2.52
(0.817 to 7.85)
Day 57 Number Analyzed 22 participants 0 participants
3.47
(1.43 to 19.2)
Day 85 Number Analyzed 22 participants 21 participants
3.70
(1.38 to 7.34)
1.39
(0.164 to 5.74)
Day 113 Number Analyzed 22 participants 0 participants
3.97
(1.96 to 16.4)
Day 141 Number Analyzed 21 participants 21 participants
4.57
(1.72 to 13)
1.35
(0.396 to 3.69)
Day 169 Number Analyzed 22 participants 0 participants
4.47
(2.04 to 12.7)
Day 197 Number Analyzed 21 participants 21 participants
4.58
(1.74 to 8.61)
1.26
(0.281 to 3.37)
Day 225 Number Analyzed 21 participants 0 participants
5.21
(1.63 to 14.3)
Day 253 Number Analyzed 20 participants 20 participants
4.96
(1.56 to 11.8)
1.45
(0.417 to 3.76)
Day 281 Number Analyzed 18 participants 0 participants
4.96
(1.30 to 12.4)
Day 309 Number Analyzed 18 participants 21 participants
5.53
(1.74 to 11.6)
1.35
(0.195 to 2.77)
Day 337 Number Analyzed 15 participants 0 participants
5.12
(2.17 to 10.5)
Day 365 Number Analyzed 18 participants 21 participants
4.50
(1.18 to 13.9)
1.45
(0.507 to 2.95)
Day 393 Number Analyzed 17 participants 0 participants
3.10
(0.220 to 9.83)
Day 421 Number Analyzed 18 participants 21 participants
3.01
(0.239 to 9.54)
1.34
(0.325 to 2.45)
3.Secondary Outcome
Title CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline
Hide Description The results of the planned analysis related to mHTT protein levels in CSF are reported
Time Frame From Baseline to Day 421
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. The data for Bi-monthly arm was not collected on days 113, 169, 225, 281, 337, 393. Here "Number Analyzed" represents number of participants from whom samples were collected and analyzed
Arm/Group Title RO7234292 Monthly RO7234292 Bimonthly
Hide Arm/Group Description:
RO7234292 was administered intrathecally every 28 days for 14 months.
RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
Overall Number of Participants Analyzed 23 23
Geometric Mean (95% Confidence Interval)
Unit of Measure: Log (10) fmol/L
Day 29 Number Analyzed 19 participants 23 participants
-27.95
(-38.37 to -15.76)
-21.84
(-33.22 to -8.52)
Day 57 Number Analyzed 23 participants 2 participants
-26.90
(-40.95 to -9.50)
10.11
(-41.68 to 107.88)
Day 85 Number Analyzed 22 participants 23 participants
-50.30
(-59.00 to -39.75)
-32.63
(-44.31 to -18.50)
Day 113 Number Analyzed 22 participants 0 participants
-49.11
(-58.77 to -37.18)
Day 141 Number Analyzed 22 participants 23 participants
-54.02
(-61.05 to -45.72)
-41.76
(-50.59 to -31.35)
Day 169 Number Analyzed 22 participants 0 participants
-42.33
(-53.66 to -28.23)
Day 197 Number Analyzed 22 participants 23 participants
-40.79
(-52.59 to -26.05)
-36.48
(-48.99 to -20.89)
Day 225 Number Analyzed 22 participants 0 participants
-47.01
(-58.69 to -32.02)
Day 253 Number Analyzed 21 participants 22 participants
-43.63
(-55.39 to -28.77)
-41.06
(-53.19 to -25.78)
Day 281 Number Analyzed 19 participants 0 participants
-40.29
(-58.63 to -13.80)
Day 309 Number Analyzed 18 participants 23 participants
-36.67
(-50.11 to -19.60)
-40.82
(-52.37 to -26.46)
Day 337 Number Analyzed 16 participants 0 participants
-42.71
(-58.93 to -20.07)
Day 365 Number Analyzed 19 participants 23 participants
-49.55
(-62.02 to -32.98)
-55.07
(-65.46 to -41.57)
Day 393 Number Analyzed 18 participants 0 participants
-41.55
(-59.46 to -15.74)
Day 421 Number Analyzed 19 participants 23 participants
-45.45
(-56.21 to -32.03)
-41.51
(-52.22 to -28.39)
4.Secondary Outcome
Title Mean Percentage Change in Ventricular Volume Boundary Shift Integral From Baseline to 15 Months
Hide Description [Not Specified]
Time Frame Baseline up to 15 months
Hide Outcome Measure Data
Hide Analysis Population Description
Here "Number of Participants Analyzed" represents number of participants from whom data were collected and analyzed. Only data that passed the QC imaging process were included in the analysis.
Arm/Group Title RO7234292 Monthly RO7234292 Bimonthly
Hide Arm/Group Description:
RO7234292 was administered intrathecally every 28 days for 14 months.
RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
Overall Number of Participants Analyzed 20 18
Mean (Standard Deviation)
Unit of Measure: Percentage change
46.09  (32.14) 18.77  (10.36)
5.Secondary Outcome
Title Mean Percentage Change in Caudate Volume Boundary Shift Integral From Baseline to 15 Months
Hide Description [Not Specified]
Time Frame Baseline up to 15 months
Hide Outcome Measure Data
Hide Analysis Population Description
Here "Number of Participants Analyzed" represents number of participants from whom data were collected and analyzed.
Arm/Group Title RO7234292 Monthly RO7234292 Bimonthly
Hide Arm/Group Description:
RO7234292 was administered intrathecally every 28 days for 14 months.
RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
Overall Number of Participants Analyzed 22 18
Mean (Standard Deviation)
Unit of Measure: Percentage change
8.64  (6.26) 5.67  (2.22)
6.Secondary Outcome
Title Mean Percentage Change in Whole Brain Volume Boundary Shift Integral From Baseline to 15 Months
Hide Description [Not Specified]
Time Frame Baseline up to 15 months
Hide Outcome Measure Data
Hide Analysis Population Description
Here "Number of Participants Analyzed" represents number of participants from whom data were collected and analyzed.
Arm/Group Title RO7234292 Monthly RO7234292 Bimonthly
Hide Arm/Group Description:
RO7234292 was administered intrathecally every 28 days for 14 months.
RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
Overall Number of Participants Analyzed 13 18
Mean (Standard Deviation)
Unit of Measure: Percentage change
1.63  (1.41) 0.89  (0.92)
7.Secondary Outcome
Title EEG Parameters: Mean Change From Baseline to 15 Months in Absolute Power [8-12Hz]
Hide Description [Not Specified]
Time Frame Baseline to 15 Months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title RO7234292 Monthly RO7234292 Bimonthly
Hide Arm/Group Description:
RO7234292 was administered intrathecally every 28 days for 14 months.
RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
Overall Number of Participants Analyzed 17 19
Mean (Standard Deviation)
Unit of Measure: log10(mircrovolts^2)
0.11  (0.18) 0.02  (0.21)
8.Secondary Outcome
Title Mean Change From Baseline in Huntington's Disease Cognitive Assessment Battery Composite Score
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title RO7234292 Monthly RO7234292 Bimonthly
Hide Arm/Group Description:
RO7234292 was administered intrathecally every 28 days for 14 months.
RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
Overall Number of Participants Analyzed 17 21
Mean (Standard Deviation)
Unit of Measure: z-score
-0.33  (0.27) -0.15  (0.23)
Time Frame From baseline to up to 18 months
Adverse Event Reporting Description Safety population comprising all participants that were randomized and received at least one dose of RO7234292
 
Arm/Group Title RO7234292 Monthly RO7234292 Bimonthly
Hide Arm/Group Description RO7234292 was administered intrathecally every 28 days for 14 months. RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
All-Cause Mortality
RO7234292 Monthly RO7234292 Bimonthly
Affected / at Risk (%) Affected / at Risk (%)
Total   1/23 (4.35%)      0/23 (0.00%)    
Hide Serious Adverse Events
RO7234292 Monthly RO7234292 Bimonthly
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/23 (17.39%)      3/23 (13.04%)    
Infections and infestations     
Myelitis  1  1/23 (4.35%)  1 0/23 (0.00%)  0
Injury, poisoning and procedural complications     
Fall  1  0/23 (0.00%)  0 1/23 (4.35%)  1
Skin laceration  1  0/23 (0.00%)  0 1/23 (4.35%)  1
Cervical vertebral fracture  1  0/23 (0.00%)  0 1/23 (4.35%)  1
Chest injury  1  1/23 (4.35%)  1 0/23 (0.00%)  0
Concussion  1  0/23 (0.00%)  0 1/23 (4.35%)  1
Meningitis chemical  1  1/23 (4.35%)  1 0/23 (0.00%)  0
Rib fracture  1  1/23 (4.35%)  1 0/23 (0.00%)  0
Spinal column injury  1  0/23 (0.00%)  0 1/23 (4.35%)  1
Thoracic vertebral fracture  1  1/23 (4.35%)  1 0/23 (0.00%)  0
Nervous system disorders     
Cerebrovascular accident  1  1/23 (4.35%)  1 0/23 (0.00%)  0
Hemiparesis  1  1/23 (4.35%)  1 0/23 (0.00%)  0
Hydrocephalus  1  1/23 (4.35%)  1 0/23 (0.00%)  0
Hyporeflexia  1  1/23 (4.35%)  1 0/23 (0.00%)  0
Neuritis  1  1/23 (4.35%)  1 0/23 (0.00%)  0
Radiculopathy  1  1/23 (4.35%)  1 0/23 (0.00%)  0
Psychiatric disorders     
Completed suicide  1  1/23 (4.35%)  1 0/23 (0.00%)  0
Suicide attempt  1  1/23 (4.35%)  1 1/23 (4.35%)  1
Respiratory, thoracic and mediastinal disorders     
Pneumothorax  1  1/23 (4.35%)  1 0/23 (0.00%)  0
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
RO7234292 Monthly RO7234292 Bimonthly
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   22/23 (95.65%)      22/23 (95.65%)    
Ear and labyrinth disorders     
Vertigo  1  2/23 (8.70%)  2 0/23 (0.00%)  0
Gastrointestinal disorders     
Diarrhoea  1  0/23 (0.00%)  0 5/23 (21.74%)  6
Nausea  1  3/23 (13.04%)  3 3/23 (13.04%)  5
Vomiting  1  2/23 (8.70%)  2 2/23 (8.70%)  2
General disorders     
Fatigue  1  3/23 (13.04%)  3 1/23 (4.35%)  1
Gait disturbance  1  6/23 (26.09%)  14 0/23 (0.00%)  0
Injection site pain  1  2/23 (8.70%)  3 4/23 (17.39%)  4
Puncture site pain  1  2/23 (8.70%)  3 2/23 (8.70%)  4
Infections and infestations     
Ear infection  1  3/23 (13.04%)  3 0/23 (0.00%)  0
Gastroenteritis  1  2/23 (8.70%)  2 1/23 (4.35%)  1
Nasopharyngitis  1  9/23 (39.13%)  14 10/23 (43.48%)  15
Upper respiratory tract infection  1  3/23 (13.04%)  4 1/23 (4.35%)  2
Urinary tract infection  1  2/23 (8.70%)  2 2/23 (8.70%)  4
Injury, poisoning and procedural complications     
Contusion  1  6/23 (26.09%)  21 5/23 (21.74%)  5
Fall  1  18/23 (78.26%)  87 12/23 (52.17%)  17
Head injury  1  2/23 (8.70%)  2 0/23 (0.00%)  0
Ligament sprain  1  1/23 (4.35%)  1 2/23 (8.70%)  2
Limb injury  1  3/23 (13.04%)  3 0/23 (0.00%)  0
Post lumbar puncture syndrome  1  4/23 (17.39%)  10 5/23 (21.74%)  6
Procedural headache  1  0/23 (0.00%)  0 2/23 (8.70%)  4
Procedural pain  1  7/23 (30.43%)  19 12/23 (52.17%)  15
Skin abrasion  1  7/23 (30.43%)  11 4/23 (17.39%)  6
Skin laceration  1  2/23 (8.70%)  2 3/23 (13.04%)  3
Investigations     
CSF protein increased  1  2/23 (8.70%)  3 1/23 (4.35%)  1
CSF white blood cell count increased  1  2/23 (8.70%)  2 0/23 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia  1  3/23 (13.04%)  4 2/23 (8.70%)  2
Back pain  1  2/23 (8.70%)  2 4/23 (17.39%)  6
Pain in extremity  1  3/23 (13.04%)  6 2/23 (8.70%)  2
Nervous system disorders     
Balance disorder  1  3/23 (13.04%)  3 1/23 (4.35%)  1
Cerebral ventricle dilatation  1  2/23 (8.70%)  2 0/23 (0.00%)  0
Dizziness  1  2/23 (8.70%)  2 2/23 (8.70%)  2
Dysarthria  1  2/23 (8.70%)  3 0/23 (0.00%)  0
Dyskinesia  1  2/23 (8.70%)  2 0/23 (0.00%)  0
Headache  1  6/23 (26.09%)  13 4/23 (17.39%)  10
Hyperkinesia  1  2/23 (8.70%)  2 0/23 (0.00%)  0
Lumbar radiculopathy  1  2/23 (8.70%)  2 0/23 (0.00%)  0
Motor dysfunction  1  3/23 (13.04%)  3 0/23 (0.00%)  0
Paraesthesia  1  2/23 (8.70%)  2 0/23 (0.00%)  0
Parkinsonism  1  2/23 (8.70%)  2 0/23 (0.00%)  0
Presyncope  1  2/23 (8.70%)  2 0/23 (0.00%)  0
Syncope  1  0/23 (0.00%)  0 2/23 (8.70%)  2
Psychiatric disorders     
Anxiety  1  2/23 (8.70%)  2 0/23 (0.00%)  0
Depressed mood  1  2/23 (8.70%)  2 2/23 (8.70%)  2
Depression  1  4/23 (17.39%)  4 2/23 (8.70%)  2
Insomnia  1  1/23 (4.35%)  1 2/23 (8.70%)  2
Irritability  1  2/23 (8.70%)  3 0/23 (0.00%)  0
Tension  1  2/23 (8.70%)  2 0/23 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Cough  1  0/23 (0.00%)  0 2/23 (8.70%)  2
Rhinorrhoea  1  1/23 (4.35%)  1 2/23 (8.70%)  3
Skin and subcutaneous tissue disorders     
Hyperhidrosis  1  2/23 (8.70%)  3 0/23 (0.00%)  0
Vascular disorders     
Haematoma  1  4/23 (17.39%)  7 2/23 (8.70%)  2
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03342053    
Other Study ID Numbers: BN40697
First Submitted: October 31, 2017
First Posted: November 14, 2017
Results First Submitted: October 7, 2020
Results First Posted: January 19, 2021
Last Update Posted: March 24, 2022