Huntington's Disease
Conditions
Brief summary
PRECISION-HD2 is a Phase 1b/2a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses of WVE-120102 in adult patients with early manifest Huntington's disease (HD) who carry a targeted single nucleotide polymorphism (SNP) rs362331 (SNP2).
Interventions
DRUGWVE-120102
WVE-120102 is a stereopure antisense oligonucleotide (ASO)
DRUGPlacebo
0.9% Sodium Chloride
Sponsors
Wave Life Sciences Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Prescreened with targeted SNP on the same allele as the pathogenic CAG expansion * Ambulatory, male or female patients aged ≥25 - ≤65 years * Clinical diagnostic motor features of HD, defined as Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Score = 4 * Early manifest HD, Stage I or Stage II based on UHDRS Total Functional Capacity Scores ≥7 and ≤13 Key
Exclusion criteria
* Malignancy or received treatment for malignancy, other than treated basal cell or squamous cell carcinoma of the skin, within the previous 5 years * Received investigational drug or implantable device in prior 3 months or investigational oligonucleotide in prior 6 months or 5 halflives of the oligonucleotide, whichever is longer * Clinically significant medical condition, unstable psychiatric symptoms, substance abuse, or pregnancy * Inability to undergo brain MRI * Bone, spine, bleeding, or other disorder that exposes the patient to risk of injury or unsuccessful lumbar puncture
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Number of Patients With Treatment-emergent Adverse Events (TEAEs) | Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts]) | All TEAEs reported or observed during the study, including TEAEs resulting from concurrent illnesses, reactions to concurrent medications, or progression of disease states |
| Safety: Number of Patients Who Experienced Severe TEAEs | Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts]) | Number of patients who experienced a severe treatment-emergent adverse event. Severity was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 |
| Safety: Number of Patients With Serious TEAEs | Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts]) | A serious TEAE is defined as any event that results in death, is immediately life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect not present at Prescreening. |
| Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs | Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts]) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics (PD): Percentage Change From Baseline in Mutant Huntingtin Protein | Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts) | Percentage change from baseline to last observation in mutant huntingtin protein |
| Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) | Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose. | Cmax of WVE-120102 in plasma |
| Clinical Effects: Total Functional Capacity (TFC) | Day 1 Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts) | Percentage change from baseline to the last measured time point in the Total Functional Capacity score, administered as part of the Unified Huntington's Disease Rating Scale (UHDRS). Total Functional Capacity is scored 13 (normal) to 0 (severe disability) |
| PK: Time of Occurrence of Cmax (Tmax) | Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose. | tmax of WVE-120102 in plasma |
| PK: Area Under the Plasma Concentration-time Curve (AUC 0-t) | Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose. | AUC 0-t from time zero to the last quantifiable concentration of WVE-120102 in plasma |
| PK: Terminal Elimination Half-life | Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose. | Terminal elimination half life of WVE-120102 in plasma (t1/2) |
Countries
Australia, Canada, Denmark, France, Germany, Poland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pooled Placebo Placebo: 0.9% Sodium Chloride | 22 |
| WVE-120102 (2 mg) WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO) | 9 |
| WVE-120102 (4 mg) WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO) | 12 |
| WVE-120102 (8 mg) WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO) | 15 |
| WVE-120102 (12 mg) WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO) | 8 |
| WVE-120102 (16 mg) WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO) | 9 |
| WVE-120102 (32 mg ) WVE-120102: WVE-120102 is a stereopure antisense oligonucleotide (ASO) | 13 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 6 |
| Overall Study | Death | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Patient decision | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Patient did not wish to comply with IC/EC | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Pooled Placebo | WVE-120102 (2 mg) | WVE-120102 (4 mg) | WVE-120102 (8 mg) | WVE-120102 (12 mg) | WVE-120102 (16 mg) | WVE-120102 (32 mg ) | Total |
|---|---|---|---|---|---|---|---|---|
| Age at disease onset | 40.18 Years STANDARD_DEVIATION 10.527 | 42.00 Years STANDARD_DEVIATION 16.363 | 41.75 Years STANDARD_DEVIATION 12.129 | 43.33 Years STANDARD_DEVIATION 9.378 | 42.50 Years STANDARD_DEVIATION 9.289 | 49.00 Years STANDARD_DEVIATION 6.652 | 48.08 Years STANDARD_DEVIATION 12.796 | 44.47 Years STANDARD_DEVIATION 11.41 |
| Age, Continuous | 46.8 Years STANDARD_DEVIATION 10.16 | 52.4 Years STANDARD_DEVIATION 11.59 | 46 Years STANDARD_DEVIATION 10.63 | 49.3 Years STANDARD_DEVIATION 10.4 | 47.1 Years STANDARD_DEVIATION 8.48 | 53.1 Years STANDARD_DEVIATION 8.33 | 54.1 Years STANDARD_DEVIATION 8.88 | 50.3 Years STANDARD_DEVIATION 9.96 |
| Diagnosis stage Stage 1 | 9 Participants | 5 Participants | 6 Participants | 8 Participants | 1 Participants | 5 Participants | 11 Participants | 45 Participants |
| Diagnosis stage Stage 2 | 13 Participants | 4 Participants | 6 Participants | 7 Participants | 7 Participants | 4 Participants | 2 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 9 Participants | 12 Participants | 15 Participants | 8 Participants | 9 Participants | 13 Participants | 87 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 9 Participants | 12 Participants | 15 Participants | 8 Participants | 9 Participants | 13 Participants | 88 Participants |
| Region of Enrollment Australia | 2 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 7 participants | 9 participants |
| Region of Enrollment Canada | 9 participants | 8 participants | 2 participants | 1 participants | 0 participants | 6 participants | 0 participants | 26 participants |
| Region of Enrollment Denmark | 0 participants | 0 participants | 2 participants | 3 participants | 0 participants | 0 participants | 0 participants | 5 participants |
| Region of Enrollment France | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Germany | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 4 participants | 5 participants |
| Region of Enrollment Poland | 4 participants | 0 participants | 4 participants | 3 participants | 0 participants | 1 participants | 1 participants | 13 participants |
| Region of Enrollment United Kingdom | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants | 2 participants | 0 participants | 4 participants |
| Region of Enrollment United States | 6 participants | 1 participants | 3 participants | 7 participants | 8 participants | 0 participants | 0 participants | 25 participants |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 7 Participants | 10 Participants | 4 Participants | 2 Participants | 6 Participants | 42 Participants |
| Sex: Female, Male Male | 14 Participants | 4 Participants | 5 Participants | 5 Participants | 4 Participants | 7 Participants | 7 Participants | 46 Participants |
| Time since initial diagnosis | 6.1 Years STANDARD_DEVIATION 5.95 | 9.9 Years STANDARD_DEVIATION 8.8 | 3.8 Years STANDARD_DEVIATION 3.62 | 5.6 Years STANDARD_DEVIATION 2.8 | 3.9 Years STANDARD_DEVIATION 3.23 | 3.2 Years STANDARD_DEVIATION 5.61 | 5.6 Years STANDARD_DEVIATION 9.28 | 5.3 Years STANDARD_DEVIATION 6.21 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 1 / 9 | 0 / 12 | 1 / 15 | 0 / 8 | 0 / 9 | 0 / 13 |
| other Total, other adverse events | 22 / 22 | 9 / 9 | 12 / 12 | 15 / 15 | 8 / 8 | 9 / 9 | 13 / 13 |
| serious Total, serious adverse events | 0 / 22 | 1 / 9 | 2 / 12 | 2 / 15 | 0 / 8 | 0 / 9 | 9 / 13 |
Outcome results
Primary
Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs
Time frame: Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
Population: No statistical analysis has been performed on these safety results
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pooled Placebo | Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs | 0 Participants |
| WVE-120102 (2 mg) | Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs | 0 Participants |
| WVE-120102 (4 mg) | Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs | 0 Participants |
| WVE-120102 (8 mg) | Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs | 0 Participants |
| WVE-120102 (12 mg) | Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs | 0 Participants |
| WVE-120102 (16 mg) | Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs | 0 Participants |
| WVE-120102 (32 mg ) | Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs | 6 Participants |
Primary
Safety: Number of Patients Who Experienced Severe TEAEs
Number of patients who experienced a severe treatment-emergent adverse event. Severity was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time frame: Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
Population: No statistical analysis has been performed on these safety results
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pooled Placebo | Safety: Number of Patients Who Experienced Severe TEAEs | 2 Participants |
| WVE-120102 (2 mg) | Safety: Number of Patients Who Experienced Severe TEAEs | 1 Participants |
| WVE-120102 (4 mg) | Safety: Number of Patients Who Experienced Severe TEAEs | 1 Participants |
| WVE-120102 (8 mg) | Safety: Number of Patients Who Experienced Severe TEAEs | 2 Participants |
| WVE-120102 (12 mg) | Safety: Number of Patients Who Experienced Severe TEAEs | 0 Participants |
| WVE-120102 (16 mg) | Safety: Number of Patients Who Experienced Severe TEAEs | 2 Participants |
| WVE-120102 (32 mg ) | Safety: Number of Patients Who Experienced Severe TEAEs | 9 Participants |
Primary
Safety: Number of Patients With Serious TEAEs
A serious TEAE is defined as any event that results in death, is immediately life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect not present at Prescreening.
Time frame: Time Frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
Population: No statistical analysis has been performed on these safety results
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pooled Placebo | Safety: Number of Patients With Serious TEAEs | 0 Participants |
| WVE-120102 (2 mg) | Safety: Number of Patients With Serious TEAEs | 1 Participants |
| WVE-120102 (4 mg) | Safety: Number of Patients With Serious TEAEs | 2 Participants |
| WVE-120102 (8 mg) | Safety: Number of Patients With Serious TEAEs | 2 Participants |
| WVE-120102 (12 mg) | Safety: Number of Patients With Serious TEAEs | 0 Participants |
| WVE-120102 (16 mg) | Safety: Number of Patients With Serious TEAEs | 0 Participants |
| WVE-120102 (32 mg ) | Safety: Number of Patients With Serious TEAEs | 9 Participants |
Primary
Safety: Number of Patients With Treatment-emergent Adverse Events (TEAEs)
All TEAEs reported or observed during the study, including TEAEs resulting from concurrent illnesses, reactions to concurrent medications, or progression of disease states
Time frame: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
Population: No statistical analysis has been performed on these safety results
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pooled Placebo | Safety: Number of Patients With Treatment-emergent Adverse Events (TEAEs) | 20 Participants |
| WVE-120102 (2 mg) | Safety: Number of Patients With Treatment-emergent Adverse Events (TEAEs) | 8 Participants |
| WVE-120102 (4 mg) | Safety: Number of Patients With Treatment-emergent Adverse Events (TEAEs) | 9 Participants |
| WVE-120102 (8 mg) | Safety: Number of Patients With Treatment-emergent Adverse Events (TEAEs) | 13 Participants |
| WVE-120102 (12 mg) | Safety: Number of Patients With Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| WVE-120102 (16 mg) | Safety: Number of Patients With Treatment-emergent Adverse Events (TEAEs) | 8 Participants |
| WVE-120102 (32 mg ) | Safety: Number of Patients With Treatment-emergent Adverse Events (TEAEs) | 13 Participants |
Secondary
Clinical Effects: Total Functional Capacity (TFC)
Percentage change from baseline to the last measured time point in the Total Functional Capacity score, administered as part of the Unified Huntington's Disease Rating Scale (UHDRS). Total Functional Capacity is scored 13 (normal) to 0 (severe disability)
Time frame: Day 1 Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts)
Population: The 12 mg dose group was not included in this analysis as these patients only received a single dose and did not attend the Day 140/Day 196 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pooled Placebo | Clinical Effects: Total Functional Capacity (TFC) | 0.0 Percent change from baseline |
| WVE-120102 (2 mg) | Clinical Effects: Total Functional Capacity (TFC) | 0.0 Percent change from baseline |
| WVE-120102 (4 mg) | Clinical Effects: Total Functional Capacity (TFC) | 0.0 Percent change from baseline |
| WVE-120102 (8 mg) | Clinical Effects: Total Functional Capacity (TFC) | -4.17 Percent change from baseline |
| WVE-120102 (12 mg) | Clinical Effects: Total Functional Capacity (TFC) | -8.33 Percent change from baseline |
| WVE-120102 (16 mg) | Clinical Effects: Total Functional Capacity (TFC) | 0.00 Percent change from baseline |
Secondary
Pharmacodynamics (PD): Percentage Change From Baseline in Mutant Huntingtin Protein
Percentage change from baseline to last observation in mutant huntingtin protein
Time frame: Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts)
Population: The 12 mg dose group was not included in this analysis as these patients only received a single dose and did not attend the Day 140/Day 196 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pooled Placebo | Pharmacodynamics (PD): Percentage Change From Baseline in Mutant Huntingtin Protein | -2.64 Percent change from baseline |
| WVE-120102 (2 mg) | Pharmacodynamics (PD): Percentage Change From Baseline in Mutant Huntingtin Protein | 3.46 Percent change from baseline |
| WVE-120102 (4 mg) | Pharmacodynamics (PD): Percentage Change From Baseline in Mutant Huntingtin Protein | -3.53 Percent change from baseline |
| WVE-120102 (8 mg) | Pharmacodynamics (PD): Percentage Change From Baseline in Mutant Huntingtin Protein | -3.45 Percent change from baseline |
| WVE-120102 (12 mg) | Pharmacodynamics (PD): Percentage Change From Baseline in Mutant Huntingtin Protein | -5.82 Percent change from baseline |
| WVE-120102 (16 mg) | Pharmacodynamics (PD): Percentage Change From Baseline in Mutant Huntingtin Protein | -2.06 Percent change from baseline |
Secondary
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax)
Cmax of WVE-120102 in plasma
Time frame: Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.
Population: Overall number of participants analyzed represents patients with at least 1 postdose plasma or CSF measurement at Day 1. The overall number for Day 112 was different and represents patients with at least 1 postdose plasma or CSF measurement at Day 112. Specimen samples collected following administration of 12 mg dose were not analyzed or tested, and therefore no data are available to be reported for this Arm/Group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) | Day 1 | 1.35 ng/mL | Standard Deviation 2.714 |
| Pooled Placebo | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) | Day 112 | 7.46 ng/mL | Standard Deviation 15.411 |
| WVE-120102 (2 mg) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) | Day 1 | 8.54 ng/mL | Standard Deviation 6.073 |
| WVE-120102 (2 mg) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) | Day 112 | 15.55 ng/mL | Standard Deviation 14.587 |
| WVE-120102 (4 mg) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) | Day 1 | 29.87 ng/mL | Standard Deviation 31.891 |
| WVE-120102 (4 mg) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) | Day 112 | 36.16 ng/mL | Standard Deviation 30.012 |
| WVE-120102 (12 mg) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) | Day 112 | 59.49 ng/mL | Standard Deviation 35.718 |
| WVE-120102 (12 mg) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) | Day 1 | 31.49 ng/mL | Standard Deviation 15.801 |
| WVE-120102 (16 mg) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) | Day 1 | 96.21 ng/mL | Standard Deviation 57.394 |
Secondary
PK: Area Under the Plasma Concentration-time Curve (AUC 0-t)
AUC 0-t from time zero to the last quantifiable concentration of WVE-120102 in plasma
Time frame: Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.
Population: Overall number of participants analyzed represents patients with at least 1 postdose plasma or CSF measurement at Day 1. The overall number for Day 112 was different and represents patients with at least 1 postdose plasma or CSF measurement at Day 112. Specimen samples collected following administration of 12 mg dose were not analyzed or tested, and therefore no data are available to be reported for this Arm/Group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | PK: Area Under the Plasma Concentration-time Curve (AUC 0-t) | Day 112 | 23.83 hr*ng/mL | Standard Deviation 23.187 |
| Pooled Placebo | PK: Area Under the Plasma Concentration-time Curve (AUC 0-t) | Day 1 | 24.65 hr*ng/mL | Standard Deviation 9.108 |
| WVE-120102 (2 mg) | PK: Area Under the Plasma Concentration-time Curve (AUC 0-t) | Day 112 | 35.47 hr*ng/mL | Standard Deviation 22.28 |
| WVE-120102 (2 mg) | PK: Area Under the Plasma Concentration-time Curve (AUC 0-t) | Day 1 | 62.05 hr*ng/mL | Standard Deviation 67.358 |
| WVE-120102 (4 mg) | PK: Area Under the Plasma Concentration-time Curve (AUC 0-t) | Day 1 | 132.44 hr*ng/mL | Standard Deviation 91.913 |
| WVE-120102 (4 mg) | PK: Area Under the Plasma Concentration-time Curve (AUC 0-t) | Day 112 | 107.83 hr*ng/mL | Standard Deviation 70.198 |
| WVE-120102 (12 mg) | PK: Area Under the Plasma Concentration-time Curve (AUC 0-t) | Day 1 | 804.92 hr*ng/mL | Standard Deviation 1456.786 |
| WVE-120102 (12 mg) | PK: Area Under the Plasma Concentration-time Curve (AUC 0-t) | Day 112 | 133.22 hr*ng/mL | Standard Deviation 67.683 |
| WVE-120102 (16 mg) | PK: Area Under the Plasma Concentration-time Curve (AUC 0-t) | Day 1 | 919.14 hr*ng/mL | Standard Deviation 271.997 |
Secondary
PK: Terminal Elimination Half-life
Terminal elimination half life of WVE-120102 in plasma (t1/2)
Time frame: Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.
Population: The t1/2 value was calculated using data from patients who had at least 3 postdose concentration values in the terminal phase. No patients had sufficient postdose samples at Day 112 to calculate t1/2 values. Specimen samples collected following administration of 12 mg dose were not analyzed or tested, and therefore no data are available to be reported for this Arm/Group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| WVE-120102 (2 mg) | PK: Terminal Elimination Half-life | 33.42 hour | Standard Deviation 30.983 |
| WVE-120102 (4 mg) | PK: Terminal Elimination Half-life | 6.23 hour | — |
| WVE-120102 (12 mg) | PK: Terminal Elimination Half-life | 13.45 hour | Standard Deviation 4.604 |
| WVE-120102 (16 mg) | PK: Terminal Elimination Half-life | 18.17 hour | Standard Deviation 20.969 |
Secondary
PK: Time of Occurrence of Cmax (Tmax)
tmax of WVE-120102 in plasma
Time frame: Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.
Population: Overall number of participants analyzed represents patients with at least 1 postdose plasma or CSF measurement at Day 1. The overall number for Day 112 was different and represents patients with at least 1 postdose plasma or CSF measurement at Day 112. Specimen samples collected following administration of 12 mg dose were not analyzed or tested, and therefore no data are available to be reported for this Arm/Group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | PK: Time of Occurrence of Cmax (Tmax) | Day 1 | 3.33 hour | Standard Deviation 7.742 |
| Pooled Placebo | PK: Time of Occurrence of Cmax (Tmax) | Day 112 | 1.22 hour | Standard Deviation 0.314 |
| WVE-120102 (2 mg) | PK: Time of Occurrence of Cmax (Tmax) | Day 112 | 1.86 hour | Standard Deviation 0.874 |
| WVE-120102 (2 mg) | PK: Time of Occurrence of Cmax (Tmax) | Day 1 | 1.26 hour | Standard Deviation 1.044 |
| WVE-120102 (4 mg) | PK: Time of Occurrence of Cmax (Tmax) | Day 112 | 2.06 hour | Standard Deviation 1.206 |
| WVE-120102 (4 mg) | PK: Time of Occurrence of Cmax (Tmax) | Day 1 | 1.77 hour | Standard Deviation 1.101 |
| WVE-120102 (12 mg) | PK: Time of Occurrence of Cmax (Tmax) | Day 112 | 1.98 hour | Standard Deviation 0.828 |
| WVE-120102 (12 mg) | PK: Time of Occurrence of Cmax (Tmax) | Day 1 | 1.77 hour | Standard Deviation 1.345 |
| WVE-120102 (16 mg) | PK: Time of Occurrence of Cmax (Tmax) | Day 1 | 3.09 hour | Standard Deviation 3.752 |