Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Participants With Parkinson's Disease

Parkinson's Disease Clinical Trial

— SPARK  

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study, With an Active-Treatment Dose-Blinded Period, to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Subjects With Parkinson's Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03318523
• Other study ID #: 228PD201
• Secondary ID: 2016-004610-95
• Status: Terminated
• Phase: Phase 2
• Start date: January 10, 2018
• Est. completion date: April 29, 2021

Study information

• Verified date: February 2022
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study is to evaluate the clinical efficacy of BIIB054 via dose response using the change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score.

The secondary objectives of the study are to evaluate the dose-related safety of BIIB054, to evaluate the clinical efficacy of BIIB054 via MDS-UPDRS total score, to assess the pharmacokinetic (PK) profile of BIIB054, to evaluate the clinical efficacy of BIIB054 based on MDS-UPDRS subparts, to evaluate the pharmacodynamic effects of BIIB054 on the integrity of nigrostriatal dopaminergic nerve terminals and to evaluate the immunogenicity of BIIB054.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 357
• Est. completion date: April 29, 2021
• Est. primary completion date: October 26, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria

• Diagnosed with Parkinson's disease (PD) within a maximum of 3 years prior to Screening.

• Score of =2.5 on the Modified Hoehn and Yahr Scale.

• Has not received any medication for the treatment of the motor symptoms of PD for at least 12 weeks prior to Day 1 and, in the opinion of the Investigator, is not expected to require PD treatment for at least 6 months following Day 1. Maximum total duration of prior PD regimens should not exceed 30 days. Stable (at least 8 weeks) dosages of medications that are used to treat conditions other than PD tremor are allowed. Further guidance will be provided by the study's Medical Monitor on a case by case basis.

• Screening dopamine transporter (DaT)/ single-photon emission computed tomography (SPECT) results consistent with neurodegenerative Parkinsonism (central reading).

• All women of childbearing potential and all men must practice highly effective contraception during the study and for 6 months after their last dose of study treatment.

Exclusion Criteria:

• Presence of freezing of gait.

• Montreal cognitive assessment (MOCA) score <23 or other significant cognitive impairment or clinical dementia that, in the opinion of the Investigator, would interfere with study evaluation.

• History of or screening brain magnetic resonance imaging (MRI) scan indicative of clinically significant abnormality, as read by central reader.

• History of severe allergic or anaphylactic reactions, or history of hypersensitivity to BIIB054 or any of the inactive ingredients in the drug product or to radioligands or iodine used in the study.

• Participation in any active immunotherapy study targeting alpha-synuclein.

• Use of allowed medications not previously specified at doses that have not been stable for at least 8 weeks before Day 1, and/or that are not expected to remain stable for the duration of the study.

• Clinically significant abnormal laboratory test values at Screening, as determined by the Investigator.

• Blood donation (1 unit or more) within 8 weeks before Day 1 (must also refrain from donating blood for the duration of the study).

NOTE : Other protocol defined Inclusion/Exclusion criteria may apply

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• Placebo
Administered as specified in the treatment arm
• BIIB054
Administered as specified in the treatment arm.

Locations

Country	Name	City	State
Austria	Research Site	Innsbruck
Canada	Montreal Neurological Institute Clinical Research Unit	Montréal	Quebec
Canada	University Health Network	Toronto	Ontario
France	Hôpital Henri Mondor	Créteil	Val De Marne
France	Hopital Roger Salengro - CHU Lille	Lille Cedex	Nord
France	CHU Nantes - Hopital Nord Laënnec	Nantes	Loire Atlantique
France	Research Site	Paris
France	Research Name	Toulouse Cedex 09	Haute Garonne
Germany	Universitaetsklinikum Aachen AOeR	Aachen	Nordrhein Westfalen
Germany	Research Site	Bochum	Nordrhein Westfalen
Germany	Paracelsus-Elena-Klinik	Kassel	Hessen
Germany	Klinikum rechts der Isar der TU Muenchen	Muenchen	Bayern
Germany	Universitaetsklinikum Ulm	Ulm	Baden Wuerttemberg
Germany	Universitaetsklinikum Wuerzburg	Wuerzburg	Bayern
Israel	Research Site	Haifa
Israel	Research Site	Tel Aviv
Italy	Ospedale Bellaria	Bologna
Italy	Azienda Ospedaliero Univ. Policlinico Gaspare Rodolico	Catania
Italy	Ospedale San Raffaele	Milano
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Seconda Università degli Studi di Napoli	Napoli
Italy	Research Site	Pisa
Italy	I.R.C.C.S. Neuromed-Istituto Neurologico Mediterraneo	Pozzilli	Isernia
Italy	IRCCS San Raffaele	Roma
Italy	Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona	Salerno
Italy	Azienda Ospedaliera Santa Maria di Terni	Terni
Spain	Biocruces Health Research Institute	Barakaldo	Vizcaya
Spain	Hospital Clinic De Barcalona	Barcelona
Spain	Hospital Santa Creu i Sant Pau	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Móstoles	Madrid
Spain	Clinica Universidad de Navarra	Pamplona	Navarra
Spain	Hospital General de Catalunya	Sant Cugat del Vallés	Barcelona
Spain	Research Site	Sevilla
United Kingdom	Research Site	Cambridge	Cambridgeshire
United Kingdom	Research Site	London
United Kingdom	Clinical Ageing Research Unit	Newcastle upon Tyne	Tyne & Wear
United Kingdom	Research Site	Oxford	Oxfordshire
United Kingdom	Salford Royal	Salford	Greater Manchester
United Kingdom	Royal Hallamshire Hospital	Sheffield	West Midlands
United States	University of Colorado Health	Aurora	Colorado
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Parkinson's Disease and Movement Disorders Centerf	Boca Raton	Florida
United States	Boston University Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern University PD and Movement Disorders Center	Chicago	Illinois
United States	Research Site	Chicago	Illinois
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Research Site	Durham	North Carolina
United States	Rocky Mountain Movement Disorders Center, PC	Englewood	Colorado
United States	Quest Research Institute	Farmington Hills	Michigan
United States	Research Site	Houston	Texas
United States	Mayo Clinic Hospital	Jacksonville	Florida
United States	University of Kansas Medical Center Research Institute	Kansas City	Kansas
United States	Booth Gardner Parkinson's Care Center at Evergreen Health	Kirkland	Washington
United States	Research Site	La Jolla	California
United States	Cedars Sinai	Los Angeles	California
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Research Site	Nashville	Tennessee
United States	Ochsner Health System	New Orleans	Louisiana
United States	NYU Langone Health Center	New York	New York
United States	Research Site	New York	New York
United States	Bioclinica Research	Orlando	Florida
United States	Research Site	Philadelphia	Pennsylvania
United States	St. Joseph's Hopsital & Medical Center- Barrow Neurological Institute	Phoenix	Arizona
United States	University of Pittsburgh Medical Center Health System	Pittsburgh	Pennsylvania
United States	University of California San Francisco Medical Center	San Francisco	California
United States	Inland Northwest Research	Spokane	Washington
United States	Research Site	Stanford	California
United States	USF Health Byrd Institute	Tampa	Florida
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Austria,  Canada,  France,  Germany,  Israel,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 52	MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were 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 was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. 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. The mean values reported are the adjusted mean values.	Baseline, Week 52
Primary	Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 72	MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were 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 was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. 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. The mean values reported are the adjusted mean values.	Baseline, Week 72
Secondary	Percentage 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 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; 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.	Up to 3 years
Secondary	Change From Baseline in MDS-UPDRS Total Score (Sum of Parts I, II, and III) at Week 96	MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were 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 was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. 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. The mean values reported are the adjusted mean values.	Baseline, Week 96
Secondary	Serum Concentration of BIIB054		Pre-dose and 1 hour post-dose of Baseline, Weeks 4, 8, 12, 16, 24, 32, 36, 44, 52, 60, 68, 84, 96, 120 and 144
Secondary	Change From Baseline in MDS-UPDRS Subpart I Score at Week 52	MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were completed by the participant (Range 0-28). For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.	Baseline, Week 52
Secondary	Change From Baseline in MDS-UPDRS Subpart I Score at Weeks 72 and 96	MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contained 6 questions and were assessed by the examiner (Range 0-24). Part IB contained 7 questions on non-motor experiences of daily living which were completed by the participant (Range 0-28). For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.	Baseline, Weeks 72 and 96
Secondary	Change From Baseline in MDS-UPDRS Subpart II Score at Week 52	MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.	Baseline, Week 52
Secondary	Change From Baseline in MDS-UPDRS Subpart II Score at Weeks 72 and 96	MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.	Baseline, Weeks 72 and 96
Secondary	Change From Baseline in MDS-UPDRS Subpart III Score at Week 52	MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. 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 was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.	Baseline, Week 52
Secondary	Change From Baseline in MDS-UPDRS Subpart III Score at Weeks 72 ad 96	MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. 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 was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicated more severe symptoms of PD. The mean values reported are the adjusted mean values.	Baseline, Weeks 72 and 96
Secondary	Change From Baseline in Striatal Binding Ratio (SBR) in the Putamen as Measured by Single-Photon Emission Computed Tomography (SPECT) Imaging of the Dopamine Transporter (DaT) at Week 52	SBR in the putamen as measured by SPECT imaging of the dopamine transporter (DaT) with 123^I-ioflupane (DaTscan™). The mean values reported are the adjusted mean values.	Baseline, Week 52
Secondary	Change From Baseline in SBR in the Striatum as Measured by SPECT Imaging of the DaT at Week 52	SBR in the striatum as measured by SPECT imaging of the DaT with 123^I-ioflupane (DaTscan™). The mean values reported are the adjusted mean values.	Baseline, Week 52
Secondary	Change From Baseline in SBR in the Caudate as Measured by SPECT Imaging of the DaT at Week 52	SBR in the caudate as measured by SPECT imaging of the DaT with 123^I-ioflupane (DaTscan™). The mean values reported are the adjusted mean values.	Baseline, Week 52
Secondary	Percentage of Participants With Anti-BIIB054 Antibodies in the Serum		Up to Week 144

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