Parkinson's DiseasePhase 1REASONNCT03976349
A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BIIB094 in Adults With Parkinson's Disease
A Phase 1 study testing BIIB094 in people with Parkinson's Disease, run by Ionis Pharmaceuticals, Inc. at 18 sites in 6 countries.
Trial summary
The primary objective of this study is to evaluate the safety and tolerability of single and multiple doses of BIIB094 administered via intrathecal (IT) injection to participants with Parkinson's Disease (PD). Read more about this study
- Who is it for?
- Ages 35 to 80 years
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- BIIB094
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 18 sitesin 6 countries
- Study dates
- 12 Aug 2019to 12 Aug 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulations.
- Diagnosed with PD within 7 years at the time of initial enrollment (i.e., at time of SAD enrollment for rollover participants), without major motor fluctuations or dyskinesia that may interfere with study treatment and assessments in the opinion of the investigator after consultation with the Sponsor.
- Modified Hoehn and Yahr Stage ≤ 3.
Who cannot join
- Montreal Cognitive Assessment (MoCA) score less than (<) 23, dementia, or other significant cognitive impairment that, in the opinion of the Investigator, would interfere with study evaluation.
- History of any brain surgery for PD or a history of focused ultrasound treatment at any time; or history of neuromodulation procedures.
- Transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year before Screening.
- History of unstable angina, myocardial infarction, chronic heart failure, or clinically significant conduction abnormalities within 1 year before Screening.
- Poorly controlled diabetes mellitus, as defined by having dosage adjustment of diabetic medication within 3 months before dosing (Day 1) or glycosylated hemoglobin value greater than or equal to (≥) 8 percent (%) at Screening.
- History or positive test result at Screening for human immunodeficiency virus.
- History or positive test result at Screening for hepatitis C virus antibody.
- NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
18 sites in 6 countries.
18 sites in 6 countries
United States7 sites
Northwestern University PD and Movement Disorders Center
Chicago, Illinois, 60611
The Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Quest Research Institute
Farmington Hills, Michigan, 48334
Alliance for Multispecialty Research
Knoxville, Tennessee, 37920
University of Pennsylvania
Philadelphia, Pennsylvania, 19107
Oregon Health and Science University
Portland, Oregon, 97239
Inland Northwest Research
Spokane, Washington, 99202
Spain5 sites
Laboratorios de Investigación Biocruces 3., Hospital de Cruces
Barakaldo, Bizkaia, 48903
Hospital General de Catalunya
Barcelona, Vizcaya, 08195
Hospital Clinic de Barcelona
Barcelona, 08036
Hospital General Universitario Gregorio Marañón
Madrid, 28007
Research Site
Seville
Canada2 sites
Montreal Neurological Institute and Hospital
Montreal, Quebec, QC H3A 2B4
Research Site
Toronto, Ontario
Norway2 sites
Neuro-SysMed Center
Bergen, 5053
St. Olav University Hospital
Trondheim, 7030
United Kingdom1 site
Queen Square (Neurology) CRF Site Institute of Neurology & the National Hospital for Neurology and Neurosurgery UCLH
London, WC1N 3BG
About this study
Official title: A Phase 1 Single- and Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of BIIB094 Administered Intrathecally to Adults With Parkinson's Disease
The primary objective of this study is to evaluate the safety and tolerability of single and multiple doses of BIIB094 administered via intrathecal (IT) injection to participants with Parkinson's Disease (PD). The secondary objective of this study is to evaluate the pharmacokinetic (PK) profile of BIIB094.The study is open for PD patients with verified presence or absence of variations in the leucine-rich repeated kinase 2 (LRRK2) gene, but also for patients without any verified PD-related genetic variant.
- Conditions
- Parkinson's Disease
- Being tested
- BIIB094, Placebo
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BIIB094Drug
Administered as specified in the treatment arm.
PlaceboDrug
Administered as specified in the treatment arm.
| Study group | Role | What they receive |
|---|---|---|
| Part A (SAD): BIIB094 Dose 1 | Experimental | Participants will receive a single IT injection of BIIB094 during Part A [Single Ascending Dose (SAD)]. Receives: Drug: BIIB094 |
| Part A (SAD): BIIB094 Dose 2 | Experimental | Participants will receive a single IT injection of BIIB094 during Part A (SAD). Receives: Drug: BIIB094 |
| Part A (SAD): BIIB094 Dose 3 | Experimental | Participants will receive a single IT injection of BIIB094 during Part A (SAD). Receives: Drug: BIIB094 |
| Part A (SAD): BIIB094 Dose 4 | Experimental | Participants will receive a single IT injection of BIIB094 during Part A (SAD). Receives: Drug: BIIB094 |
| Part A (SAD): BIIB094 Dose 5 | Experimental | Participants will receive a single IT injection of BIIB094 during Part A (SAD). Receives: Drug: BIIB094 |
| Part A (SAD): BIIB094 Dose 6 | Experimental | Participants will receive a single IT injection of BIIB094 during Part A (SAD). Receives: Drug: BIIB094 |
| Part B (MAD): BIIB094 Dose 1 | Experimental | Participants will receive a single IT injection of BIIB094 on multiple days during Part B [Multiple Ascending Dose (MAD)]. Receives: Drug: BIIB094 |
| Part B (MAD): BIIB094 (Non LRRK2) Dose 2 | Experimental | Participants [Non leucine-rich repeat kinase 2 (Non LRRK2)] will receive a single IT injection of BIIB094 on multiple days during Part B (MAD). Receives: Drug: BIIB094 |
| Part B (MAD): BIIB094 (LRRK2) Dose 2 | Experimental | Participants (LRRK2) will receive a single IT injection of BIIB094 on multiple days during Part B (MAD). Receives: Drug: BIIB094 |
| Part B (MAD): BIIB094 (Non LRRK2) Dose 3 | Experimental | Participants (Non LRRK2) will receive a single IT injection of BIIB094 on multiple days during Part B (MAD). Receives: Drug: BIIB094 |
| Part B (MAD): BIIB094 (LRRK2) Dose 3 | Experimental | Participants (LRRK2) will receive a single IT injection of BIIB094 on multiple days during Part B (MAD). Receives: Drug: BIIB094 |
| Part A (SAD): Matching Placebo | Placebo comparator | Participants will receive matching placebo during Part A [Single Ascending Dose (SAD)]. Receives: Drug: Placebo |
| Part B (MAD): Matching Placebo | Placebo comparator | Participants will receive matching placebo on multiple days during Part B (MAD). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An 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 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); however, this does not include an event that, had it occurred in a more severe form, might have caused death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event.
Measured: Part A: Screening (Day -42) up to Day 85, Part B: Screening (Day -77) up to Day 253
Secondary outcomes (6)
Serum Concentrations of BIIB094
Measured: Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of BIIB094
Measured: Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) of BIIB094
Measured: Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
Maximum Concentration (Cmax) of BIIB094
Measured: Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
Time to Reach Maximum Concentration (Tmax) of BIIB094
Measured: Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
Terminal Elimination Half-Life (t1/2) of BIIB094
Measured: Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2019
- Study start12 Aug 2019
- Primary completion12 Aug 2024
- Study completion12 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03976349
- Sponsor's protocol ID
- 254PD101
- Other IDs
- 2018-002995-42, 2018
- Acronym
- REASON
- Status last verified
- Sep 2025
- First submitted
- 4 Jun 2019
- Last updated
- 23 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mabrouk OS, Tichler B, Arnold HM, Thoma EC, Alexanian SM, Chen J, Liu TY, Hirschhorn B, Llorens Arenas R, Annand JW, Kapadnis U, Shomo AA, Glajch KE, Ferber K, Moroishi Y, Czerkowicz J, Inra J, Postuma RB, Gurevich T, Mir P, Morris HR, Aldred J, Brodsky MA, Ellenbogen A, Larson D, Tolleson CM, Siderowf A, Tzoulis C, Balaguer E, Marti MJ, Zhao HT, Kordasiewicz HB, Lane R, Hirst WD, Fradette S, Graham DL. LRRK2-targeting antisense oligonucleotide in Parkinson's disease: a phase 1 randomized controlled trial. Nat Med. 2026 Apr;32(4):1421-1431. doi: 10.1038/s41591-026-04262-4. Epub 2026 Mar 24.
PubMed 41876647
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Single- and Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of BIIB094 Administered Intrathecally to Adults With Parkinson's Disease
- ClinicalTrials.gov ID
- NCT03976349
- Acronym / sponsor ID
- REASON / 254PD101
- Conditions
- Parkinson's Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 12 Aug 2019 (actual)
- Primary completion
- 12 Aug 2024 (actual)
- Study completion
- 12 Aug 2024 (actual)
- First posted
- 6 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to evaluate the safety and tolerability of single and multiple doses of BIIB094 administered via intrathecal (IT) injection to participants with Parkinson's Disease (PD). The secondary objective of this study is to evaluate the pharmacokinetic (PK) profile of BIIB094.The study is open for PD patients with verified presence or absence of variations in the leucine-rich repeated kinase 2 (LRRK2) gene, but also for patients without any verified PD-related genetic variant.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 13
| Arm | Type | Receives |
|---|---|---|
| Part A (SAD): BIIB094 Dose 1 | Experimental | Drug: BIIB094Participants will receive a single IT injection of BIIB094 during Part A [Single Ascending Dose (SAD)]. |
| Part A (SAD): BIIB094 Dose 2 | Experimental | Drug: BIIB094Participants will receive a single IT injection of BIIB094 during Part A (SAD). |
| Part A (SAD): BIIB094 Dose 3 | Experimental | Drug: BIIB094Participants will receive a single IT injection of BIIB094 during Part A (SAD). |
| Part A (SAD): BIIB094 Dose 4 | Experimental | Drug: BIIB094Participants will receive a single IT injection of BIIB094 during Part A (SAD). |
| Part A (SAD): BIIB094 Dose 5 | Experimental | Drug: BIIB094Participants will receive a single IT injection of BIIB094 during Part A (SAD). |
| Part A (SAD): BIIB094 Dose 6 | Experimental | Drug: BIIB094Participants will receive a single IT injection of BIIB094 during Part A (SAD). |
| Part B (MAD): BIIB094 Dose 1 | Experimental | Drug: BIIB094Participants will receive a single IT injection of BIIB094 on multiple days during Part B [Multiple Ascending Dose (MAD)]. |
| Part B (MAD): BIIB094 (Non LRRK2) Dose 2 | Experimental | Drug: BIIB094Participants [Non leucine-rich repeat kinase 2 (Non LRRK2)] will receive a single IT injection of BIIB094 on multiple days during Part B (MAD). |
| Part B (MAD): BIIB094 (LRRK2) Dose 2 | Experimental | Drug: BIIB094Participants (LRRK2) will receive a single IT injection of BIIB094 on multiple days during Part B (MAD). |
| Part B (MAD): BIIB094 (Non LRRK2) Dose 3 | Experimental | Drug: BIIB094Participants (Non LRRK2) will receive a single IT injection of BIIB094 on multiple days during Part B (MAD). |
| Part B (MAD): BIIB094 (LRRK2) Dose 3 | Experimental | Drug: BIIB094Participants (LRRK2) will receive a single IT injection of BIIB094 on multiple days during Part B (MAD). |
| Part A (SAD): Matching Placebo | Placebo comparator | Drug: PlaceboParticipants will receive matching placebo during Part A [Single Ascending Dose (SAD)]. |
| Part B (MAD): Matching Placebo | Placebo comparator | Drug: PlaceboParticipants will receive matching placebo on multiple days during Part B (MAD). |
Who may qualify
- Ages
- 35 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulations.
- Diagnosed with PD within 7 years at the time of initial enrollment (i.e., at time of SAD enrollment for rollover participants), without major motor fluctuations or dyskinesia that may interfere with study treatment and assessments in the opinion of the investigator after consultation with the Sponsor.
- Modified Hoehn and Yahr Stage ≤ 3.
Key exclusion criteria (8 listed)
- Montreal Cognitive Assessment (MoCA) score less than (<) 23, dementia, or other significant cognitive impairment that, in the opinion of the Investigator, would interfere with study evaluation.
- History of any brain surgery for PD or a history of focused ultrasound treatment at any time; or history of neuromodulation procedures.
- Transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year before Screening.
- History of unstable angina, myocardial infarction, chronic heart failure, or clinically significant conduction abnormalities within 1 year before Screening.
- Poorly controlled diabetes mellitus, as defined by having dosage adjustment of diabetic medication within 3 months before dosing (Day 1) or glycosylated hemoglobin value greater than or equal to (≥) 8 percent (%) at Screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BIIB094Administered as specified in the treatment arm. | Drug | Part A (SAD): BIIB094 Dose 1, Part A (SAD): BIIB094 Dose 2, Part A (SAD): BIIB094 Dose 3, Part A (SAD): BIIB094 Dose 4, Part A (SAD): BIIB094 Dose 5, Part A (SAD): BIIB094 Dose 6, Part B (MAD): BIIB094 (LRRK2) Dose 2, Part B (MAD): BIIB094 (LRRK2) Dose 3, Part B (MAD): BIIB094 (Non LRRK2) Dose 2, Part B (MAD): BIIB094 (Non LRRK2) Dose 3, Part B (MAD): BIIB094 Dose 1 |
| PlaceboAdministered as specified in the treatment arm. | Drug | Part A (SAD): Matching Placebo, Part B (MAD): Matching Placebo |
Primary outcome
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Part A: Screening (Day -42) up to Day 85, Part B: Screening (Day -77) up to Day 253
An 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 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); however, this does not include an event that, had it occurred in a more severe form, might have caused death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event.
6 secondary outcomes
Serum Concentrations of BIIB094
Time frame: Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of BIIB094
Time frame: Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) of BIIB094
Time frame: Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
Maximum Concentration (Cmax) of BIIB094
Time frame: Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
Time to Reach Maximum Concentration (Tmax) of BIIB094
Time frame: Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
Terminal Elimination Half-Life (t1/2) of BIIB094
Time frame: Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2025.
- Derived from this study: PubMed 41876647Mabrouk OS, Tichler B, Arnold HM, Thoma EC, Alexanian SM, Chen J, Liu TY, Hirschhorn B, Llorens Arenas R, Annand JW, Kapadnis U, Shomo AA, Glajch KE, Ferber K, Moroishi Y, Czerkowicz J, Inra J, Postuma RB, Gurevich T, Mir P, Morris HR, Aldred J, Brodsky MA, Ellenbogen A, Larson D, Tolleson CM, Siderowf A, Tzoulis C, Balaguer E, Marti MJ, Zhao HT, Kordasiewicz HB, Lane R, Hirst WD, Fradette S, Graham DL. LRRK2-targeting antisense oligonucleotide in Parkinson's disease: a phase 1 randomized controlled trial. Nat Med. 2026 Apr;32(4):1421-1431. doi: 10.1038/s41591-026-04262-4. Epub 2026 Mar 24.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
18 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BIIB094 in people with Parkinson's Disease, run by Ionis Pharmaceuticals, Inc. at 18 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, Spain, Canada, Norway, Israel and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Part A: Screening (Day -42) up to Day 85, Part B: Screening (Day -77) up to Day 253). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03976349, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2025.