Huntington Disease
Conditions
Brief summary
WVE-HDSNP1-002 is an open-label extension (OLE) study to evaluate the safety, tolerability, PK, PD, and clinical effects of WVE-120101 in adult patients with early manifest HD who carry a targeted single nucleotide polymorphism, rs362307 (SNP1). To participate in the study, patients must have completed the Phase 1b/2a clinical study WVE-HDSNP1-001.
Interventions
DRUGWVE-120101
WVE-120101 is a stereopure antisense oligonucleotide (ASO). It is administered monthly via intrathecal injection.
Sponsors
Wave Life Sciences Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * 1\. Patient successfully completed the Phase 1b/2a study with WVE-120101, WVE-HDSNP1-001. Key
Exclusion criteria
* 1\. Received an investigational drug other than WVE-120101, including an investigational oligonucleotide, within the past 1 year or 5 half-lives of the drug, whichever is longer. * 2\. Inability to undergo brain MRI (with or without sedation). * 3\. Clinically significant medical finding on the physical examination other than HD that, in the judgment of the Investigator, will make the patient unsuitable for participation in and/or completion of the study procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety: Number of Patients With Treatment-emergent AEs (TEAEs) | First dose received (Day 1) through the Study Termination visit (maximum of 45 weeks of treatment) |
| Safety: Number of Patients With a Severe TEAE | First dose received (Day 1) through the Study Termination visit (maximum of 45 weeks of treatment |
| Safety: Number of Patients With Serious TEAEs | First dose received (Day 1) through the Study Termination visit (maximum of 45 weeks of treatment |
| Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs | First dose received (Day 1) through the Study Termination visit (maximum of 45 weeks of treatment |
Countries
Australia, Canada, Denmark, France, Germany, Poland, United Kingdom
Participant flow
Pre-assignment details
In the original OLE study protocol, patients who were in the 2 and 4 mg dose cohorts in the Phase 1b/2a study were to be enrolled into the 4 or 8 mg dose group in this study. Patients in the 8 and 16 mg dose cohorts in WVE-HDSNP1-001 continued to receive that dose. As of Amendment 1.0 of this protocol, all new patients were to be enrolled at a dose level of at least 16 mg. All current patents were dose modified to 16 or 32 mg.
Participants by arm
| Arm | Count |
|---|---|
| 4 mg WVE-120101 Enrolled at 4 mg WVE-120101 dose level | 3 |
| 16 mg WVE-120101 Enrolled at 12 mg WVE-120101 dose level | 24 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Termination of Study by Sponsor | 2 | 21 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | 4 mg WVE-120101 | 16 mg WVE-120101 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 24 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 24 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 24 Participants | 27 Participants |
| Region of Enrollment Australia | 0 participants | 8 participants | 8 participants |
| Region of Enrollment Canada | 3 participants | 3 participants | 6 participants |
| Region of Enrollment Denmark | 0 participants | 2 participants | 2 participants |
| Region of Enrollment France | 0 participants | 2 participants | 2 participants |
| Region of Enrollment Poland | 0 participants | 9 participants | 9 participants |
| Sex: Female, Male Female | 2 Participants | 15 Participants | 17 Participants |
| Sex: Female, Male Male | 1 Participants | 9 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 2 / 27 | 0 / 5 |
| other Total, other adverse events | 2 / 3 | 16 / 27 | 2 / 5 |
| serious Total, serious adverse events | 0 / 3 | 3 / 27 | 1 / 5 |
Outcome results
Primary
Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs
Time frame: First dose received (Day 1) through the Study Termination visit (maximum of 45 weeks of treatment
Population: Patients treated at more than one dose level (e.g., initial dose and after dose modification) are included in each applicable dose group. Adverse events are counted in the dose the patient was receiving at the time of onset.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 4 mg WVE-120101 | Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs | 0 Participants |
| 16 mg WVE-120101 | Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs | 1 Participants |
| 32 mg WVE-120101 | Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs | 0 Participants |
Primary
Safety: Number of Patients With a Severe TEAE
Time frame: First dose received (Day 1) through the Study Termination visit (maximum of 45 weeks of treatment
Population: Patients treated at more than one dose level (e.g., initial dose and after dose modification) are included in each applicable dose group. Adverse events are counted in the dose the patient was receiving at the time of onset.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 4 mg WVE-120101 | Safety: Number of Patients With a Severe TEAE | 0 Participants |
| 16 mg WVE-120101 | Safety: Number of Patients With a Severe TEAE | 5 Participants |
| 32 mg WVE-120101 | Safety: Number of Patients With a Severe TEAE | 0 Participants |
Primary
Safety: Number of Patients With Serious TEAEs
Time frame: First dose received (Day 1) through the Study Termination visit (maximum of 45 weeks of treatment
Population: Patients treated at more than one dose level (e.g., initial dose and after dose modification) are included in each applicable dose group. Adverse events are counted in the dose the patient was receiving at the time of onset.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 4 mg WVE-120101 | Safety: Number of Patients With Serious TEAEs | 0 Participants |
| 16 mg WVE-120101 | Safety: Number of Patients With Serious TEAEs | 3 Participants |
| 32 mg WVE-120101 | Safety: Number of Patients With Serious TEAEs | 1 Participants |
Primary
Safety: Number of Patients With Treatment-emergent AEs (TEAEs)
Time frame: First dose received (Day 1) through the Study Termination visit (maximum of 45 weeks of treatment)
Population: Patients treated at more than one dose level (e.g., initial dose and after dose modification) are included in each applicable dose group. Adverse events are counted in the dose the patient was receiving at the time of onset.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 4 mg WVE-120101 | Safety: Number of Patients With Treatment-emergent AEs (TEAEs) | 2 Participants |
| 16 mg WVE-120101 | Safety: Number of Patients With Treatment-emergent AEs (TEAEs) | 17 Participants |
| 32 mg WVE-120101 | Safety: Number of Patients With Treatment-emergent AEs (TEAEs) | 2 Participants |