Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as RO7234292 (RG6042), Tominersen
RO7234292 · 5 trials · 3 indications
The reported are the treatment-emergent AEs with an onset date up to 5 months after last study drug intake.
C-SSRS is to assess suicidal ideation and behavior. 4 constructs measured: severity of ideation, intensity of ideation, behavior, and lethality of actual suicide attempts. Yes/No data collected for 10 categories, composite endpoints based on the categories are followed over time to monitor safety. Composite endpoint of suicidal ideation (1-5), n and (%) are the number and % of who experience any of the five suicidal ideation events at least once after receiving the first dose of study medication. Composite endpoint of suicidal behavior (6-10), n and (%) are the number and percent of patients who experience any 1of 5 suicidal behavior events at least 1 after receiving the 5 dose of study medication. Composite endpoint of suicidal ideation or behavior (1-10), n and (%) are the number and % of patients who experience any 1 the 10 suicidal ideation or behavior events at least once after receiving the first dose of study medication.
MoCA contains a series of basic assessments, including attention and visuospatial tasks. The total score ranges from 0-30, where lower scores indicate greater impairment. MOCA01-Total scores are reported. The data presented are absolute scores for baseline and change from baseline for post-baseline assessments. All Arms except Tominersen 120mg Q4W (Period 1) belong to the Milestone Period 2.
cUHDRS includes the Total Functional Capacity (range, 0-13; higher score means better functioning), Total Motor Score (range, 0-124; higher score means worse motor severity), Symbol Digit Modality Test (range, 0-110, correctly paired numbers-symbols in 90 seconds; higher score means better cognitive performance), and Stroop Word Reading (range, 0-no max value, correctly read colour words in 45 seconds; higher score means better cognitive performance) scores. A z-score for each test is calculated, which alone can be used to describe relationship between an individual's test score and the mean score of a target population. A z-score of 0 is the mean, and ±1 is 1 standard deviation from the mean. For cUHDRS, z-scores of each test are summed, whereby a higher cUHDRS score is better (score of -3.06-no max value) and a change of ≥1.2 is a meaningful worsening, shown to track functional decline.
Total Functional Capacity (TFC) Scores are reported at Weeks 21 and 69. Total Functional Capacity Score ranges from 0 to 13, with a higher score representing better functioning.
Change in scores on the scale.
Change in scores on the scale.
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.
NA represents: insufficient number of participants with events.
NA represents:insufficient number of participants with events
CSF Mutant Huntingtin Protein (fmol/L) values at time point visits are reported.
| Arm | Type | Description |
|---|---|---|
| RO7234292 (RG6042) Q8W | EXPERIMENTAL | Participants who received open-label RO7234292 Q4W in a preceding study or who received RO7234292 Q4W in this study may be randomly allocated to receive RO7234292 Q8W. Participants who previously received open-label of RO7234292 Q8W in a preceding study or are currently receiving RO7234292 Q8W in this study will receive RO7234292 Q8W. Participants who previously received placebo, or did not previously receive treatment with RO7234292 or received short-term treatment with a treatment-free follow-up period may be randomly allocated to receive RO7234292 Q8W. Participants who previously received blinded placebo Q8W may receive RO7234292 Q8W. Participants who received blinded RO7234292 Q8W will receive open-label RO7234929 Q8W. Participants who received blinded placebo Q8W may receive RO7234292 Q8W. Participants who received blinded RO7234292 Q4W or blinded placebo Q4W may be randomly allocated to receive open-label of RO7234292 Q8W. |
| RO7234292 (RG6042) Q16W | EXPERIMENTAL | Participants who previously received open-label RO7234292 Q4W in a preceding study or who received RO7234292 Q4W in this study may be randomly allocated to receive RO7234292 Q16W. Participants who previously received placebo in a preceding study or did not previously receive treatment with RO7234292 or received short-term treatment with a treatment-free follow-up period may be randomly allocated to receive RO7234292 Q16W. Participants who previously received blinded placebo Q8W will receive RO7234292 Q8W. Participants who previously received blinded RO7234292 Q16W will receive open-label RO7234292 Q16W. Participants who received blinded RO7234292 Q4W or blinded placebo Q4W may be randomly allocated to receive open-label of RO7234292 Q16W. Participants who previously received open-label RO7234292 Q16W will receive open-label RO7234292 Q16W. |
| RO7234292 Q8W | EXPERIMENTAL | RO4234292 is administered intrathecally every 8 weeks. |
| RO7234292 Q16W | EXPERIMENTAL | RO7234292 is administered intrathecally every 16 weeks. Participants in this arm will also receive placebo at alternate weeks to keep the blind. |
| Placebo | PLACEBO_COMPARATOR | Placebo will be administered every 8 weeks by IT injection. |
| Tominersen 60 milligrams (mg) | EXPERIMENTAL | 60 mg tominersen administered intrathecally (IT) every 16 weeks (Q16W). Tominersen will be administered in the DB period and the OLE period. |
| Tominersen 100 mg | EXPERIMENTAL | 100 mg tominersen administered IT, Q16W. Tominersen will be administered in the DB period and the OLE period. |
| RO7234292 Monthly | EXPERIMENTAL | RO7234292 is administered every 28 days intrathecally for 14 months. |
| RO7234292 Bimonthly | EXPERIMENTAL | RO7234292 is administered every 56 days intrathecally for 14 months following 2 monthly doses to serve as a loading dose. |
| Dose level 1 of RO7234292 (RG6042) | EXPERIMENTAL | Participants will receive dose level 1 of RO7234292 (RG6042) intrathecally on Day 1 and Day 29. |
| Dose level 2 of RO7234292 (RG6042) | EXPERIMENTAL | Participants will receive dose level 2 of RO7234292 (RG6042) intrathecally on Day 1 and Day 29. |
| Dose level 3 of RO7234292 (RG6042) | EXPERIMENTAL | Participants will receive dose level 3 of RO7234292 (RG6042) intrathecally on Day 1 and Day 29. |
| Name | Type | Description |
|---|---|---|
| RO7234292 (RG6042) | DRUG | Intrathecal injection |
| RO7234292 | DRUG | Intrathecal injection |
| Placebo | DRUG | Intrathecal injection |
| Tominersen | DRUG | Tominersen will be administered at the dose and schedule specified in the protocol. |
Inclusion Criteria: * Prior enrollment in a Roche-sponsored or Genentech-sponsored study in HD for the RO7234292 (RG6042) development program that made provision for entry into an OLE study * For women of childbearing potential: agreement to remain abstinent or use contraceptive measures * For men:...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Novartis AG Sponsored ADR | NVS | 2 | PHASE3 | Votoplam |
| Neurocrine Biosciences, Inc. | NBIX | 1 | PHASE3 | Valbenazine |
| Hoffmann-La Roche | RHHBY | 3 | PHASE2 | Tominersen, RG6496, SPK-10001 |
| Alnylam Pharmaceuticals, Inc | ALNY | 1 | PHASE1 | ALN-HTT02 |
| uniQure N.V. | QURE | 2 | PHASE1 | AMT-130 |
| Sarepta Therapeutics, Inc. | SRPT | 1 | PHASE1 | SRP-1005 |
RO7234292 is being developed for the treatment of Huntington disease, a rare inherited neurodegenerative disorder. It is an investigational therapy studied in adults with manifest Huntington disease, and all four of its clinical trials enrolled participants with this condition rather than healthy volunteers.
RO7234292 is developed by Roche Holding AG, which trades under the ticker RHHBY. Roche and Genentech sponsored the clinical studies of the drug, including the Phase 3 efficacy trial and the open-label extension study in Huntington disease participants.
RO7234292 has been studied in Phase 3 clinical development for Huntington disease. Four trials have been completed, including two Phase 3 studies, one Phase 2 study, and one Phase 1 study, with a combined enrollment of 1,193 participants.
RO7234292 has been evaluated in four completed trials: NCT03761849, a Phase 3 efficacy and safety study in 899 participants with manifest Huntington disease; NCT03842969, a Phase 3 open-label extension study in 236 participants; NCT03342053, a Phase 2 study in 46 participants; and NCT04000594, a Phase 1 pharmacokinetics and pharmacodynamics study in 12 participants.
Yes, RO7234292 is also known as RG6042. The two names refer to the same investigational compound, and Roche study titles list it as RO7234292 (RG6042). An earlier Phase 2 study also referenced the compound as ISIS 443139.
RO7234292 was given by intrathecal administration in its clinical studies, meaning it was delivered directly into the cerebrospinal fluid. The trials assessed pharmacokinetics and pharmacodynamics in cerebrospinal fluid and plasma alongside safety and tolerability in patients with Huntington disease.