Trial Outcomes & Findings for 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) (NCT NCT03342053)

NCT ID: NCT03342053

Last Updated: 2022-03-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

46 participants

Primary outcome timeframe

From baseline up to 18 months

Results posted on

2022-03-24

Participant Flow

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

Participant milestones

Participant milestones
Measure	RO7234292 Monthly RO7234292 was administered intrathecally every 28 days for 14 months.	RO7234292 Bimonthly RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
Overall Study STARTED	23	23
Overall Study COMPLETED	21	22
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	RO7234292 Monthly RO7234292 was administered intrathecally every 28 days for 14 months.	RO7234292 Bimonthly RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
Overall Study Adverse Event	2	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

One participant's race is known, was reported but cannot be classified in Roche database

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: From baseline up to 18 months

Population: Safety population comprising all participants that were randomized and received at least one dose of RO7234292.

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.

Outcome measures

Outcome measures
Measure	RO7234292 Monthly n=23 Participants RO7234292 was administered intrathecally every 28 days for 14 months.	RO7234292 Bimonthly n=23 Participants RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
Percentage of Participants With Adverse Events	100 Percentage of participants	95.7 Percentage of participants

SECONDARY outcome

Timeframe: From baseline to Day 421

Population: 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.

Outcome measures

Outcome measures
Measure	RO7234292 Monthly n=23 Participants RO7234292 was administered intrathecally every 28 days for 14 months.	RO7234292 Bimonthly n=23 Participants RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis) Day 29	2.59 ng/mL Interval 1.31 to 12.7	2.52 ng/mL Interval 0.817 to 7.85
RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis) Day 57	3.47 ng/mL Interval 1.43 to 19.2	—
RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis) Day 85	3.70 ng/mL Interval 1.38 to 7.34	1.39 ng/mL Interval 0.164 to 5.74
RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis) Day 113	3.97 ng/mL Interval 1.96 to 16.4	—
RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis) Day 141	4.57 ng/mL Interval 1.72 to 13.0	1.35 ng/mL Interval 0.396 to 3.69
RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis) Day 169	4.47 ng/mL Interval 2.04 to 12.7	—
RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis) Day 197	4.58 ng/mL Interval 1.74 to 8.61	1.26 ng/mL Interval 0.281 to 3.37
RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis) Day 225	5.21 ng/mL Interval 1.63 to 14.3	—
RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis) Day 253	4.96 ng/mL Interval 1.56 to 11.8	1.45 ng/mL Interval 0.417 to 3.76
RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis) Day 281	4.96 ng/mL Interval 1.3 to 12.4	—
RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis) Day 309	5.53 ng/mL Interval 1.74 to 11.6	1.35 ng/mL Interval 0.195 to 2.77
RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis) Day 337	5.12 ng/mL Interval 2.17 to 10.5	—
RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis) Day 365	4.50 ng/mL Interval 1.18 to 13.9	1.45 ng/mL Interval 0.507 to 2.95
RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis) Day 393	3.10 ng/mL Interval 0.22 to 9.83	—
RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis) Day 421	3.01 ng/mL Interval 0.239 to 9.54	1.34 ng/mL Interval 0.325 to 2.45

SECONDARY outcome

Timeframe: From Baseline to Day 421

Population: 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

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

Outcome measures

Outcome measures
Measure	RO7234292 Monthly n=23 Participants RO7234292 was administered intrathecally every 28 days for 14 months.	RO7234292 Bimonthly n=23 Participants RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline Day 57	-26.90 Log (10) fmol/L Interval -40.95 to -9.5	10.11 Log (10) fmol/L Interval -41.68 to 107.88
CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline Day 309	-36.67 Log (10) fmol/L Interval -50.11 to -19.6	-40.82 Log (10) fmol/L Interval -52.37 to -26.46
CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline Day 29	-27.95 Log (10) fmol/L Interval -38.37 to -15.76	-21.84 Log (10) fmol/L Interval -33.22 to -8.52
CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline Day 85	-50.30 Log (10) fmol/L Interval -59.0 to -39.75	-32.63 Log (10) fmol/L Interval -44.31 to -18.5
CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline Day 113	-49.11 Log (10) fmol/L Interval -58.77 to -37.18	—
CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline Day 141	-54.02 Log (10) fmol/L Interval -61.05 to -45.72	-41.76 Log (10) fmol/L Interval -50.59 to -31.35
CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline Day 169	-42.33 Log (10) fmol/L Interval -53.66 to -28.23	—
CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline Day 197	-40.79 Log (10) fmol/L Interval -52.59 to -26.05	-36.48 Log (10) fmol/L Interval -48.99 to -20.89
CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline Day 225	-47.01 Log (10) fmol/L Interval -58.69 to -32.02	—
CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline Day 253	-43.63 Log (10) fmol/L Interval -55.39 to -28.77	-41.06 Log (10) fmol/L Interval -53.19 to -25.78
CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline Day 281	-40.29 Log (10) fmol/L Interval -58.63 to -13.8	—
CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline Day 337	-42.71 Log (10) fmol/L Interval -58.93 to -20.07	—
CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline Day 365	-49.55 Log (10) fmol/L Interval -62.02 to -32.98	-55.07 Log (10) fmol/L Interval -65.46 to -41.57
CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline Day 393	-41.55 Log (10) fmol/L Interval -59.46 to -15.74	—
CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline Day 421	-45.45 Log (10) fmol/L Interval -56.21 to -32.03	-41.51 Log (10) fmol/L Interval -52.22 to -28.39

SECONDARY outcome

Timeframe: Baseline up to 15 months

Population: 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.

Outcome measures

Outcome measures
Measure	RO7234292 Monthly n=20 Participants RO7234292 was administered intrathecally every 28 days for 14 months.	RO7234292 Bimonthly n=18 Participants RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
Mean Percentage Change in Ventricular Volume Boundary Shift Integral From Baseline to 15 Months	46.09 Percentage change Standard Deviation 32.14	18.77 Percentage change Standard Deviation 10.36

SECONDARY outcome

Timeframe: Baseline up to 15 months

Population: Here "Number of Participants Analyzed" represents number of participants from whom data were collected and analyzed.

Outcome measures

Outcome measures
Measure	RO7234292 Monthly n=22 Participants RO7234292 was administered intrathecally every 28 days for 14 months.	RO7234292 Bimonthly n=18 Participants RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
Mean Percentage Change in Caudate Volume Boundary Shift Integral From Baseline to 15 Months	8.64 Percentage change Standard Deviation 6.26	5.67 Percentage change Standard Deviation 2.22

SECONDARY outcome

Timeframe: Baseline up to 15 months

Population: Here "Number of Participants Analyzed" represents number of participants from whom data were collected and analyzed.

Outcome measures

Outcome measures
Measure	RO7234292 Monthly n=13 Participants RO7234292 was administered intrathecally every 28 days for 14 months.	RO7234292 Bimonthly n=18 Participants RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
Mean Percentage Change in Whole Brain Volume Boundary Shift Integral From Baseline to 15 Months	1.63 Percentage change Standard Deviation 1.41	0.89 Percentage change Standard Deviation 0.92

SECONDARY outcome

Timeframe: Baseline to 15 Months

Outcome measures

Outcome measures
Measure	RO7234292 Monthly n=17 Participants RO7234292 was administered intrathecally every 28 days for 14 months.	RO7234292 Bimonthly n=19 Participants RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
EEG Parameters: Mean Change From Baseline to 15 Months in Absolute Power [8-12Hz]	0.11 log10(mircrovolts^2) Standard Deviation 0.18	0.02 log10(mircrovolts^2) Standard Deviation 0.21

SECONDARY outcome

Timeframe: Baseline to 15 Months

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.

Outcome measures

Outcome measures
Measure	RO7234292 Monthly n=17 Participants RO7234292 was administered intrathecally every 28 days for 14 months.	RO7234292 Bimonthly n=21 Participants RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
Mean Change From Baseline in Huntington's Disease Cognitive Assessment Battery Composite Score	-0.33 z-score Standard Deviation 0.27	-0.15 z-score Standard Deviation 0.23

Adverse Events

RO7234292 Monthly

Serious events: 4 serious events

Other events: 22 other events

Deaths: 1 deaths

RO7234292 Bimonthly

Serious events: 3 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	RO7234292 Monthly n=23 Participants RO7234292 was administered intrathecally every 28 days for 14 months.	RO7234292 Bimonthly n=23 Participants RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.	Total n=46 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	23 Participants n=5 Participants	20 Participants n=7 Participants	43 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants • One participant's race is known, was reported but cannot be classified in Roche database	0 Participants n=7 Participants • One participant's race is known, was reported but cannot be classified in Roche database	0 Participants n=5 Participants • One participant's race is known, was reported but cannot be classified in Roche database
Age, Continuous	47.7 Years STANDARD_DEVIATION 9.3 • n=5 Participants	49.5 Years STANDARD_DEVIATION 11.3 • n=7 Participants	48.6 Years STANDARD_DEVIATION 10.3 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	13 Participants n=7 Participants	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=5 Participants	23 Participants n=7 Participants	46 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants • One participant's race is known, was reported but cannot be classified in Roche database	0 Participants n=7 Participants • One participant's race is known, was reported but cannot be classified in Roche database	0 Participants n=5 Participants • One participant's race is known, was reported but cannot be classified in Roche database
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants • One participant's race is known, was reported but cannot be classified in Roche database	0 Participants n=7 Participants • One participant's race is known, was reported but cannot be classified in Roche database	0 Participants n=5 Participants • One participant's race is known, was reported but cannot be classified in Roche database
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants • One participant's race is known, was reported but cannot be classified in Roche database	0 Participants n=7 Participants • One participant's race is known, was reported but cannot be classified in Roche database	0 Participants n=5 Participants • One participant's race is known, was reported but cannot be classified in Roche database
Race/Ethnicity, Customized White	22 Participants n=5 Participants • One participant's race is known, was reported but cannot be classified in Roche database	23 Participants n=7 Participants • One participant's race is known, was reported but cannot be classified in Roche database	45 Participants n=5 Participants • One participant's race is known, was reported but cannot be classified in Roche database
Race/Ethnicity, Customized More than one race	0 Participants n=5 Participants • One participant's race is known, was reported but cannot be classified in Roche database	0 Participants n=7 Participants • One participant's race is known, was reported but cannot be classified in Roche database	0 Participants n=5 Participants • One participant's race is known, was reported but cannot be classified in Roche database
Race/Ethnicity, Customized Other	1 Participants n=5 Participants • One participant's race is known, was reported but cannot be classified in Roche database	0 Participants n=7 Participants • One participant's race is known, was reported but cannot be classified in Roche database	1 Participants n=5 Participants • One participant's race is known, was reported but cannot be classified in Roche database

Measure	RO7234292 Monthly n=23 participants at risk RO7234292 was administered intrathecally every 28 days for 14 months.	RO7234292 Bimonthly n=23 participants at risk RO7234292 was administered intrathecally every 56 days for 14 months following 2 monthly doses to serve as a loading dose.
Injury, poisoning and procedural complications Fall	0.00% 0/23 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292
Injury, poisoning and procedural complications Skin laceration	0.00% 0/23 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292
Infections and infestations Myelitis	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292	0.00% 0/23 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292
Injury, poisoning and procedural complications Cervical vertebral fracture	0.00% 0/23 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292
Injury, poisoning and procedural complications Chest injury	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292	0.00% 0/23 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292
Injury, poisoning and procedural complications Concussion	0.00% 0/23 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292
Injury, poisoning and procedural complications Meningitis chemical	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292	0.00% 0/23 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292
Injury, poisoning and procedural complications Rib fracture	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292	0.00% 0/23 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292
Injury, poisoning and procedural complications Spinal column injury	0.00% 0/23 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292
Injury, poisoning and procedural complications Thoracic vertebral fracture	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292	0.00% 0/23 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292
Nervous system disorders Cerebrovascular accident	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292	0.00% 0/23 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292
Nervous system disorders Hemiparesis	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292	0.00% 0/23 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292
Nervous system disorders Hydrocephalus	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292	0.00% 0/23 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292
Nervous system disorders Hyporeflexia	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292	0.00% 0/23 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292
Nervous system disorders Neuritis	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292	0.00% 0/23 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292
Nervous system disorders Radiculopathy	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292	0.00% 0/23 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292
Psychiatric disorders Completed suicide	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292	0.00% 0/23 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292
Psychiatric disorders Suicide attempt	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292
Respiratory, thoracic and mediastinal disorders Pneumothorax	4.3% 1/23 • Number of events 1 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292	0.00% 0/23 • From baseline to up to 18 months Safety population comprising all participants that were randomized and received at least one dose of RO7234292