Parkinson Disease
Conditions
Brief summary
In this study, researchers will learn more about a study drug called BIIB122 in participants with early-stage Parkinson's disease (PD). The study will focus on participants with a specific genetic variant in their LRRK2 gene. The main question researchers are trying to answer is if taking BIIB122 slows the worsening of PD more than placebo in the early stages of PD. To help answer this question, researchers will use a questionnaire called the Movement Disorder Society-Unified Parkinson's Disease Rating Scale, also known as the MDS-UPDRS. * The MDS-UPDRS measures impairment and disability in people living with PD. It was created in the 1980s and is one of the most used rating scales for PD symptoms. * The MDS-UPDRS has 4 parts, and a higher score means more severe PD symptoms. * Part I assesses non-motor experiences of daily living, including but not limited to memory loss, problems sleeping, pain, depression, and anxiety. * Part II measures motor experiences of daily living. * Part III is the results of a motor symptoms exam by a medical professional. * Part IV records PD complications caused by motor symptoms. Researchers will also learn more about the safety of BIIB122. A description of how the study will be done is given below. * Participants will take BIIB122 or a placebo as tablets by mouth. A placebo looks like the study drug but contains no real medicine. * Participants will be in the study for 103 weeks to 187 weeks. This includes the screening and follow-up periods. * Participants will take BIIB122 or placebo 1 time a day for 96 to 180 weeks. * Participants can continue to take certain medications for PD. Participants must be on the same dose of medication for at least 90 days before the study begins. * Participants will visit the clinic less often as the study continues, ranging every 4 weeks to every 24 weeks.
Detailed description
BIIB122 is an investigational central nervous system-penetrant small molecule inhibitor of LRRK2 kinase
Interventions
DRUGBIIB122
Administered as specified in the treatment arm.
Administered as specified in the treatment arm.
Sponsors
Denali Therapeutics Inc.
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Clinical diagnosis of PD meeting the Movement Disorder Society Clinical Diagnostic Criteria within 5 years of the Screening Visit, inclusive, and at least 30 years of age at the time of diagnosis * Modified Hoehn and Yahr scale (mHY), Stages 1 to 2.5 (in OFF state), inclusive, at Screening * MDS-UPDRS Parts II and III (in OFF state) combined score ≤40 at Screening * Screening genetic test results verifying the presence of a pathogenic leucine-rich repeat kinase 2 (LRRK2) variant Key
Exclusion criteria
* Clinically significant neurologic disorder other than PD, including, but not limited to, stroke, dementia, or seizure within 5 years of Screening Visit, in the opinion of the Investigator * Clinical evidence of atypical parkinsonism (e.g., multiple-system atrophy or progressive supranuclear palsy) or evidence of drug-induced parkinsonism NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Confirmed Worsening in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III | From Week 96 to Week 180 | Time to confirmed worsening is defined as a worsening event sustained over 2 consecutive assessments. MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assesses motor experiences of daily living (range 0-52). It contains 13 questions which are to be completed by the participant. Part III assesses the motor signs of PD and is administered by the rater (range 0-132). Part III contains 33 scores based on 18 items. For each question, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Part II and III combined score equals the sum of Parts II and III (range 0-184). A higher score indicates more severe symptoms of Parkinson's disease (PD). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From the first dose (Day 1) of the study drug up to the end of follow-up (up to 336 days) | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death; in the view of the investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect or is a medically important event. |
| Time to Confirmed Worsening in MDS-UPDRS Part II Score | From Week 96 to Week 180 | Time to confirmed worsening is defined as a worsening event sustained over 2 consecutive assessments. MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assesses motor experiences of daily living (range 0-52). It contains 13 questions which are to be completed by the participant. For each question, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Part II score ranges from 0-52. A higher score indicates more severe symptoms of PD. |
| Change From Baseline in MDS-UPDRS Parts II and III Combined Score at Week 96 | Baseline, Week 96 | MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assesses motor experiences of daily living (range 0-52). It contains 13 questions which are to be completed by the participant. Part III assesses the motor signs of PD and is administered by the rater (range 0-132). Part III contains 33 scores based on 18 items. For each question, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Part II and III combined score equals the sum of Parts II and III (range 0-184). A higher score indicates more severe symptoms of PD. |
| Time to Confirmed Worsening in Modified Schwab and England Activities of Daily Living Scale (mSE-ADL) Score | From Week 96 to Week 180 | Time to confirmed worsening is defined as a worsening event sustained over 2 consecutive assessments. The mSE-ADL scale reflects the speed, ease, and independence with which an individual performs daily activities or personal chores with 100% indicating total independence, falling to 0%, which indicates a state of complete dependence. The individual is asked to rate his or her function using an 11-point scale (10% increments), from 100% (completely independent; able to do all chores without slowness, difficulty, or impairment; essentially normal; unaware of any difficulty) to 0% (vegetative functions such as swallowing, bladder and bowels are not functioning; bedridden). The lower the score, the worse the functional status. |
| Change From Baseline in MDS-UPDRS Parts I, II, and III Combined Score at Week 96 | Baseline, Week 96 | The MDS-UPDRS is a multimodal scale consisting of four parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contains 6 questions and are assessed by the examiner (Range 0-24). Part IB contains 7 questions on non-motor experiences of daily living which was completed by the participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. Part III assessed the motor signs of PD and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. The MDS-UPDRS Total Score equals the sum of Parts I,II, and III (Range: 0-236). A higher score indicated more severe symptoms of PD. |
Countries
France, Germany, Italy, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at multiple investigative sites in the United States and the United Kingdom from 26 Aug 2022 to 27 Jul 2023.
Pre-assignment details
A total of 7 participants were enrolled and treated in the study, but none of the participants completed it.
Participants by arm
| Arm | Count |
|---|---|
| BIIB 122 or Matching-placebo (Pooled) Participants either received BIIB122 225 mg or BIIB122-matching placebo tablets, orally, QD for up to 290 days. | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Study Terminated by Sponsor | 2 | 4 |
Baseline characteristics
| Characteristic | BIIB 122 or Matching-placebo (Pooled) |
|---|---|
| Age, Continuous | 66.9 years STANDARD_DEVIATION 10.7 |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 7 Participants |
| Race/Ethnicity, Customized Race White | 7 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 5 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
Time to Confirmed Worsening in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III
Time to confirmed worsening is defined as a worsening event sustained over 2 consecutive assessments. MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assesses motor experiences of daily living (range 0-52). It contains 13 questions which are to be completed by the participant. Part III assesses the motor signs of PD and is administered by the rater (range 0-132). Part III contains 33 scores based on 18 items. For each question, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Part II and III combined score equals the sum of Parts II and III (range 0-184). A higher score indicates more severe symptoms of Parkinson's disease (PD).
Time frame: From Week 96 to Week 180
Population: Based on the low enrolment number and to protect and maintain participant privacy/confidentiality, no data is reported, as only 1 participant completed post-baseline visit for clinical efficacy outcomes.
Secondary
Change From Baseline in MDS-UPDRS Parts II and III Combined Score at Week 96
MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assesses motor experiences of daily living (range 0-52). It contains 13 questions which are to be completed by the participant. Part III assesses the motor signs of PD and is administered by the rater (range 0-132). Part III contains 33 scores based on 18 items. For each question, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Part II and III combined score equals the sum of Parts II and III (range 0-184). A higher score indicates more severe symptoms of PD.
Time frame: Baseline, Week 96
Population: Due to the early termination of the study (before week 48), sufficient data were not collected for the outcome measure analysis.
Secondary
Change From Baseline in MDS-UPDRS Parts I, II, and III Combined Score at Week 96
The MDS-UPDRS is a multimodal scale consisting of four parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contains 6 questions and are assessed by the examiner (Range 0-24). Part IB contains 7 questions on non-motor experiences of daily living which was completed by the participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. Part III assessed the motor signs of PD and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. The MDS-UPDRS Total Score equals the sum of Parts I,II, and III (Range: 0-236). A higher score indicated more severe symptoms of PD.
Time frame: Baseline, Week 96
Population: Due to the early termination of the study (before week 48), sufficient data were not collected for the outcome measure analysis.
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death; in the view of the investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect or is a medically important event.
Time frame: From the first dose (Day 1) of the study drug up to the end of follow-up (up to 336 days)
Population: Safety analysis set included all randomized participants who had received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | AEs | 2 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| BIIB122 225 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | AEs | 3 Participants |
| BIIB122 225 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
Secondary
Time to Confirmed Worsening in MDS-UPDRS Part II Score
Time to confirmed worsening is defined as a worsening event sustained over 2 consecutive assessments. MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assesses motor experiences of daily living (range 0-52). It contains 13 questions which are to be completed by the participant. For each question, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Part II score ranges from 0-52. A higher score indicates more severe symptoms of PD.
Time frame: From Week 96 to Week 180
Population: Based on the low enrolment number and to protect and maintain participant privacy/confidentiality, no data is reported, as only 1 participant completed post-baseline visit for clinical efficacy outcomes.
Secondary
Time to Confirmed Worsening in Modified Schwab and England Activities of Daily Living Scale (mSE-ADL) Score
Time to confirmed worsening is defined as a worsening event sustained over 2 consecutive assessments. The mSE-ADL scale reflects the speed, ease, and independence with which an individual performs daily activities or personal chores with 100% indicating total independence, falling to 0%, which indicates a state of complete dependence. The individual is asked to rate his or her function using an 11-point scale (10% increments), from 100% (completely independent; able to do all chores without slowness, difficulty, or impairment; essentially normal; unaware of any difficulty) to 0% (vegetative functions such as swallowing, bladder and bowels are not functioning; bedridden). The lower the score, the worse the functional status.
Time frame: From Week 96 to Week 180
Population: Based on the low enrolment number and to protect and maintain participant privacy/confidentiality, no data is reported, as only 1 participant completed post-baseline visit for clinical efficacy outcomes.