Clinical Trial Highlights: Individual Trials

The Clinical Trials Highlights section in JPD is devoted to raising awareness of the clinical trial landscape in Parkinson’s, promoting discussion and progress in the conduct and outcome of studies. On this page, you can search the individual trials that have been featured. An overview of all articles that have been published in JPD can be found on the main Clinical Trials Highlights page here.

A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Flexible-Dose, 27-Week Trial to Evaluate the Efficacy, Safety, and Tolerability of Tavapadon in Early Parkinson’s Disease (TEMPO-2 Trial)

Status: 
Active, No Longer Recruiting
Sponsor: 
Cerevel Therapeutics, LLC
Enrollment: 
296
Study Design: 
This is a phase 3, double-blind, randomized, placebo-controlled, parallel-group, flexible-dose, 27-week trial designed to evaluate the efficacy, safety, and tolerability of tavapadon in participants with early PD. The inclusion and exclusion criteria for TEMPO-2 are the same as TEMPO-1. This study has two arms: 1. Experimental arm where participants will be randomized to receive tavapadon anywhere from 5 to 15mg daily for 27 weeks; and 2. Placebo comparator arm where participants will receive a placebo for 27 weeks. The study is being conducted at seven sites across the USA, different to the TEMPO-1 study sites.
Rationale: 
The primary and secondary outcome measures for TEMPO-2 are similar to TEMPO-1 with minor changes in duration. The primary outcome remains the same as TEMPO-1 and will assess the change in MDS-UPDRS part II and III combined score up to 27 weeks from baseline. The secondary measures are the same as TEMPO-1 except for the change in MDS-UPDRS I, II, and III individual scores will be assessed up to 29 weeks.

Multidisciplinary Study of Novel NMDA Modulation for Neurodegenerative Disorder

Status: 
Recruiting
Sponsor: 
China Medical University Hospital
Enrollment: 
60
Study Design: 
This is a phase 2, randomized, parallel assigned, placebo-controlled, and a quadruple blinded interventional study assessing the safety and efficacy of DAAOI-P in PD participants with dementia. The study is being conducted at the CMU Hospital in Taiwan. The study includes two arms, a placebo arm and an experimental arm where participants will receive the investigational drug DAAOI-P [250-1500mg]. Adult participants with PD between the ages of 50 and 90 years with clinically diagnosed PDD according to the criteria of the Movement Disorders Society will be included. Both probable and possible PDD will be included in this study. Co-existing medical conditions or medications that can independently cause cognitive impairment preventing a reliable diagnosis of PDD, will be excluded. Participants who have been on anticholinergics within 30 days of recruitment will also be excluded.
Rationale: 
The primary outcome focuses on improvement in gait and neuropsychiatric symptoms as measured by the change in the UPDRS. Secondary outcome measures except the neuroimaging will be assessed at baseline, 8, 16, and 24 weeks and include: 1. Change in gait function as measured by the cyclogram of gait; 2. Fall assessment test of China Medical University hospital; 3. Change in cognitive function as measured by Alzheimer’s Disease Assessment Scale - Cognitive Subscale (ADAS-Cog), Behavioral pathology in Alzheimer’s Disease rating scale (Behave-AD), and clinical dementia rating (CDR) scale; 4. Change in Neuropsychiatric inventory scale; 5. Change in the PDQ-39 scale; 6. Change in perceptual discriminability, emotion recognition accuracy, and imitation probability; 7. Neuroimaging, including structural MRI, resting-state functional MRI, and working memory fMRI, assessed at baseline and 24 weeks; 8. Changes in mismatch negativity in an electroencephalogram; 9. Changes in transcranial magnetic stimulation assessments.
Comments: 
NMDA modulation has been the target of several medications for CI. No prior studies of DAAOI for PD-CI were found. The outcome of this Phase 2 study centers on efficacy assessments with a focus on the gait and cognition. The efficacy of DAAOI in PDD is yet to be established.

A Multicenter, Open-Label Study to Evaluate Tolerability and Efficacy of Orally Administered ENT-01 for the Treatment of Parkinson’s Disease Dementia

Status: 
Active, No Longer Recruiting
Sponsor: 
Enterin Inc
Enrollment: 
40
Study Design: 
This is a phase 1, multicenter (3 sites in the USA), open-label study assessing the safety and tolerability of ENT-01 in participants with PDD. The study will recruit participants aged 30-90 years with a clinical diagnosis of PD with dementia. Only MoCA score of < 24 will be included. Standard exclusionary criteria are applied. All participants will receive the study drug as daily oral dosing for 10 weeks. The study will require 5 visits. Participants will be allowed to adjust the medication dose as specified in the protocol.
Rationale: 
The primary outcome measure is cognition improvement using the Dementia Severity Rating Scale (DSRS), assessed at baseline and after 10 weeks of treatment. The secondary outcomes, also assessed at baseline and after 10 weeks of treatment are: 1. Change in the MoCA; 2. Change in symptoms adapted for Parkinson’s disease (SAPS-PD). This measures the frequency and/or severity of hallucinations and delusions; 3. Change in Neuropsychiatric Inventory (NPI) and Caregiver Distress (NPI-D); and 4. Change in Parkinson’s Disease Questionnaire-39 (PDQ-39). The study will also assess other outcome measures: 1. Change in MDS-UPDRS; 2. Change in skin temperature-determined circadian rhythm; and 3. Change in body weight.
Comments: 
This study intends to explore the ability of ENT-01 to influence α-synuclein aggregation and the subsequent impact on cognitive symptoms. The timeframe to assess this effect is 10 weeks. Open label design of the study will preclude any meaningful conclusions regarding potential efficacy. Together with the RASMET (NCT03047629) and KARMET (NCT02781791 and NCT04483479) studies, Enterin are building a solid base of patient experience with ENT-01.

ANAVEX®2-73 Study in Parkinson’s Disease Dementia

Status: 
Active, No Longer Recruiting
Sponsor: 
Anavex Life Sciences Corp.
Enrollment: 
120
Study Design: 
The study is double-blind, randomized, placebo-controlled, and multicenter (25 sites). There are three arms, two with active treatment at low and high doses, and placebo, delivered as oral capsules. The trial is recruiting participants over the age of 50, with a MoCA score between 13 and 23.
Rationale: 
There are two primary and two secondary outcome measures, all measured at 14 weeks. The primary ones are: 1. Change from baseline to end of treatment in cognitive drug research (CDR) computerized assessment system for Continuity of Attention; and 2. Number of participants with treatment-related adverse events as assessed by CTCAE (com-mon terminology criteria for adverse events) v4.0. Secondary outcomes are: 1. Change from baseline to end of treatment as measured by the MDS-UPDRS part III score (motor scores); and 2. Incidence of sleep disorders symptom checklist (SDS-CL-25).
Comments: 
There are three indications under investigation for ANAVEX®2-73 - Rett syndrome, Alzheimer’s disease, and PD, bringing more clinical experience with this drug. The primary cognitive outcome measure is tightly focused on the attention domain. The MoCA score inclusion criterion is a relatively wide range, including both MCI and PDD.

Effect of LY3154207 on Cognition in Mild-to-Moderate Dementia Due to Lewy Body Dementia (LBD) Associated With Idiopathic Parkinson’s Disease (PD) or Dementia With Lewy Bodies (DLB)

Status: 
Completed
Sponsor: 
Eli Lilly and Company
Enrollment: 
344
Study Design: 
This is a phase 2, randomized, parallel assigned, double-blinded, interventional study assessing the safety and efficacy of the study drug, LY3154207, in participants with Lewy body dementia. Participants between the ages of 40 and 85 years with a clinical diagnosis of PD or dementia with Lewy bodies deemed to have increased functional impairment due to a decline in cognitive functions are eligible for inclusion. The MoCA score must be between 10-23. Certain medication classes are allowed if the participants have been on a stable dose for 3 weeks before the screening and expected to remain on a stable dose throughout the study. The medications allowed include antihypertensives, antiparkinson, antidepressants, medications for cognition and psychosis [clozapine, quetiapine, and pimavanserin]. Participants on antipsychotics other than listed above and anticholinergics will be excluded. Participants are required to have reliable caregivers. Standard exclusionary criteria apply. Participants will be randomly assigned to one of the four arms: 1. Experimental arm 1: high dose of the investigational drug orally; 2. Experimental arm 2: mid dose of the investigational drug orally; 3. Experimental arm 3: low dose of the investigational drug orally; and 4. Placebo arm.
Rationale: 
The primary outcome measure will assess the change at 12 weeks from baseline in the continuity of attention composite score of the cognitive drug research computerized cognition battery (CDR-CCB). The secondary outcome measures assess the change in various scales at 12 weeks from baseline. The scales included mostly assess the cognitive and psychiatric domains. Additional measures assess the change in the MDS-UPDRS total score, vital signs, and even the pharmacokinetics.
Comments: 
D1R is a potentially interesting target for the management of both PD motor and non-motor disability. While there are other D1R agonists being explored for motor benefits, LY3154207 focuses on cognition. The phase 2 has completed enrolment and is awaiting results.

A Study to Evaluate NYX-458 in Subjects With Mild Cognitive Impairment Associated With Parkinson’s Disease

Status: 
Active, No Longer Recruiting
Sponsor: 
Aptinyx
Enrollment: 
135
Study Design: 
This is a phase 2, randomized, parallel-group, triple blinded study evaluating the safety and tolerability of NYX-458 in MCI associated with PD. Participants between 50-80 years of age with a primary diagnosis of MCI associated with PD will be eligible for inclusion. They should be on a stable antiparkinsonian medication regimen. Participants with MoCA <17 and those meeting criteria for dementia will be excluded. The exclusion criteria also include an ambiguous point of excluding those on medication with primarily central nervous system activities. The study will be conducted over 16-18 weeks which will include the following, in sequential order: 1. Screening: 2 to 4-weeks; 2. Intervention: 12-weeks; and 3. Follow up: 2-weeks. The trial is studying the safety profile of 3 dosing regimens of the investigation drug. The participants will be randomized to one of the following four arms: 1. Experimental: where participants will receive a 10mg daily dose for 12 weeks; 2. Experimental: where participants will receive a 30mg daily dose for 12 weeks; 3. Experimental: where participants will receive 100mg daily dose for 12 weeks; and 4. Placebo. The study is being conducted at multiple sites across the USA.
Rationale: 
The primary outcome measure focuses on safety by assessing the number of participants with adverse events. Secondary outcomes aim to measure efficacy across multiple cognitive scales though not well outlined in the clinicaltrials.gov.
Comments: 
NMDAR is an interesting potential target, and NYX-458 is a promising molecule based on preclinical studies. The current clinical trial, as expected and rightly so, is focusing on the safety and tolerability of 3 doses of NYX-458. Whether preclinical benefits will translate into clinically meaningful effect is yet to be determined with further studies, contingent upon Phase 2 safety results.

Ambroxol as a Treatment for Parkinson’s Disease Dementia

Status: 
Recruiting
Sponsor: 
Lawson Health Research Institute
Enrollment: 
75
Study Design: 
Randomized, double-blind, parallel assignment, with a treatment time of 52 weeks, carried out at a single center. There are three arms in the study: Arm 1: Ambroxol high dose (1050mg per day); Arm 2: Ambroxol low dose (525mg per day); and Arm 3: Placebo. Participants with a MoCA score between 16 and 24 and age >50 are being recruited. The GBA1 gene in each participant will be sequenced, but the mutation status is not an inclusion or exclusion criterion.
Rationale: 
Primary outcome measures, taken at baseline, 26 weeks and 52 weeks are: 1. Changes in the Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS-cog); and 2. Changes in the ADCS-Clinician’s Global Impression of Change (CGIC). Secondary outcome measures include a spectrum of scales measuring motor and non-motor disability, specific domains of cognition, CSF and peripheral ambroxol PK profile, and GCAse levels. The study also includes MRI imaging outcomes measuring brain ventricle volume and hippocampal atrophy (baseline and week 52): 1. Changes in the MoCA (baseline, week 26 and week 52); 2. Changes in the Clinical Dementia Rating Scale (CDR) (baseline, week 26 and week 52); 3. Changes in the Trail Making Test (baseline, week 26 and week 52); 4. Change in the Parkinson’s Disease-Cognitive Rating Scale (PD-CRS) (baseline, week 26 and week 52); 5. Changes in the Stroop Test (baseline, week 26 and week 52); 6. Changes in the Unified Parkinson’s disease Rating Scale motor subsection (UP-DRS-III) (baseline, week 26 and week 52); 7. Changes in the Purdue Pegboard (baseline, week 26 and week 52); 8. Changes in the Timed Up and Go (baseline, week 26 and week 52); 9. Change in Quantitative Movement Testing - gait assessment on electronic mat (Zeno Walkway System) (baseline, week 26 and week 52); 10. Changes in Cerebrospinal Fluid (CSF) biomarkers - levels of ±-synuclein (pg/ml), Tau (pg/ml), phospho-Tau (pg/ml) and beta amyloid-42 (pg/ml) (baseline, week12 and week 52); 11. Changes in Magnetic Resonance Imaging (MRI) - brain ventricle volume (cm3) and hippocampal atrophy (cm3) (baseline and week 52); 12. Changes in the Mini-Mental State Examination (screening, baseline, week 4, week 6, week 12, week 18, week 26, week 34, week 42, week 52); 13. Changes in GCase in lymphocytes (baseline, week 2, week 4, week 6, week 8, week 12, week 18, week 26, week 34, week 42, week 52); 14. Changes in Plasma Ambroxol levels (baseline, week 2, week 4, week 6, week 8, week 12, week 18, week 26, week 34, week 42, week 52); 15. Mayo Fluctuation Questionnaire (baseline, 26 weeks and 52 weeks).
Comments: 
A more detailed description of the trial has been published. Targeting the GBA pathway is of great interest, and a number of programs are in development. This study focuses specifically on the impact on cognition. The secondary outcome measures are comprehensive and require a high number of participant visits (11) and procedures, including three lumbar punctures. The dose of ambroxol under evaluation is 1,050mg per day, approximately 15mg/kg/day. This is much higher than the OTC dose. An even higher dose, 1,260mg, was used in the phase 2 efficacy trial described by Mullins et al. [4]. In the Lawson Health study, the number of 75mg tablets per day is up to 14 per day for the higher dose. The number of tablets to be taken each day by participants with PDD or MCI may thus be a challenge for compliance. However, one inclusion criterion requires the presence of a responsible caregiver for at least 4 days per week.

Effect of Donepezil on Cognition in Parkinson’s Disease with Mild Cognitive Impairment (PD-MCI)

Status: 
Active, No Longer Recruiting
Sponsor: 
Yonsei University
Enrollment: 
80
Study Design: 
This is an open-label and single center trial. The target dosage is 10mg unless not tolerated, in which case the dosage to be taken will be 5mg. The treatment duration is 48 weeks.
Rationale: 
The single primary outcome is the rate of cognitive decline using the Korean version of the MMSE measured at baseline and 48 weeks. The five secondary outcome measures are: 1. Change in cognitive decline (24, 48, and 72 weeks); 2. Change in UPDRS parts I-IV (24, 48, and 72 weeks); 3. Brain structure (cortical thickness, and subcortical volume and shape) and default mode and network with conventional and functional MRI (48 weeks); 4. Brain functional connectivity using digital electroencephalography (48 weeks); and 5. Comprehensive neuropsychological test using the Seoul Neuropsychological Screening Battery (SNSB) (48 weeks).
Comments: 
The rationale for the Yonsei University trial is that the cholinergic deficits seen in PDD are also present in PD-MCI. The hope is that earlier intervention with donepezil may delay the onset of PDD. The outcome measures are aiming to correlate the results of clinical measurement with structural change via fMRI and EEG. In parallel, the progression of other PD symptoms will be measured using UPDRS. The treatment duration is 48 weeks, although changes in cognitive decline and UPDRS will be measured again at 72 weeks. The trial is recruiting participants with a confirmed diagnosis of PD-MCI aged over 40. It was due to finish in 2019, although no results appear to have been published yet.

A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Flexible-Dose, 27-Week Trial to Evaluate the Efficacy, Safety, and Tolerability of Tavapadon as Adjunctive Therapy for PD in Levodopa-Treated Adults With Motor Fluctuations (TEMPO-3)

Status: 
Not Yet Recruiting
Sponsor: 
Cerevel Therapeutics, LLC
Enrollment: 
368
Study Design: 
This is a phase 3, double-blind, randomized, placebo-controlled, parallel-group, flexible-dose, 27-week trial designed to evaluate the efficacy, safety, and tolerability of tavapadon as adjunctive therapy in advanced PD participants already on levodopa and with motor fluctuations. The inclusion criteria for TEMPO-3 is different to TEMPO-1 and 2 for obvious reasons. It will include clinically diagnosed PD participants between age 40-80 years with “on” state H&Y stage between 2–3. Participants should be levodopa responsive, taking at least 400mg/day and be on a stable dose for at least four weeks before screening. Other adjunctive therapies are allowed if started >90 days before signing the consent and is expected to be stable throughout the study. Standard exclusionary criteria apply. Participants from prior tavapadon trial will be excluded. This study has two arms: 1. Experimental arm where participants will be randomized to receive tavapadon anywhere from 5 to 15mg daily for 27 weeks; 2. Placebo comparator arm where participants will receive a placebo for 27 weeks. The study is being conducted at 21 sites across the USA.
Rationale: 
All the measures will assess the change from baseline. The primary outcome will assess the change in the total “on” time without troublesome dyskinesia based on the Hauser diary entries at 27 weeks. The secondary outcomes will measure the following: 1. Change in the total ‘Off’ times at 27 weeks; 2. Change in total “on” and “off” times without troublesome dyskine-sia at weeks 2, 5, 8, 11, 14, 18, 22, 26, and 27; and 3. Change in MDS-UPDRS part I, II, and III individual scores at 27 weeks.
Comments: 
Tavapadon is an exciting molecule with the potential for therapeutic benefit by modulating the direct pathways in the basal ganglia circuitry. However, the drug has had a few setbacks in phase 2 studies. The advanced stage of the disease and fixed medication dose may account for the lack of efficacy in the interim analysis of NCT02687542. TEMPO-3, likely learning from phase 2 results, will study the molecule as adjunctive therapy with flexible dosing. Notably, the NCT02847650 trial showed a safe profile with a positive change in motor scoring in early PD, but the results were not clinically meaningful. Given the results were from a Phase 2 study with partial data analysis, we will be on the lookout for TEMPO-1 and 2 study results. While D1R is a potential target for PD-CI, TEMPO studies do not include any secondary cognitive measures and exclude participants with MoCA less <26 for early PD and those with troublesome CI in advanced PD. Their focus remains on the motor profile of PD.

A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, 27-Week Trial to Evaluate the Efficacy, Safety, and Tolerability of Two Fixed Doses of Tavapadon in Early Parkinson’s Disease (TEMPO-1 TRIAL)

Status: 
Active, No Longer Recruiting
Sponsor: 
Cerevel Therapeutics, LLC
Enrollment: 
522
Study Design: 
This is a phase 3, randomized, parallel assigned, double-blinded, placebo-controlled, fixed-dose study evaluating the efficacy, safety and tolerability, and pharmacokinetics of two fixed doses of tavapadon in participants with early PD. Clinically diagnosed PD participants between age 40-80 years with H&Y stage less than 2 and within 3 years of disease duration from the time of diagnosis are eligible to participate. The MDS-UPDRS part II and III scores should be ≥2 and 10, respectively, at the time of screening. Participants should be dopaminergic drug naïve and be willing to refrain from non-permitted PD medications. Participants who have been taking dopaminergic agents but for less than three months and at least two months before signing consent will be eligible for inclusion. The use of MAO-Inhibitors is allowed. Apart from standard exclusionary criteria, participants with impulse control disorders, certain neuropsychiatric symptoms, and MoCA <26 will be excluded. The participants will be randomized to one of the three arms, which are: 1. Experimental arms: there will be two experimental arms where participants will be randomized to receive tavapadon titrated to either 5mg or 15mg orally daily for 27 weeks; and 2. Comparator arm where participants will receive a matching placebo orally once a day for 27 weeks. The study is being conducted at 11 sites across the USA.
Rationale: 
The primary outcome assesses the change in MDS-UPDRS parts II and III combined score up to 27 weeks from baseline. The secondary measures include the following: 1. Percentage of responders with ‘Much improved’ or ‘Very much im-proved’ rating on the Participant global impression of change (PGIC) up to 27 weeks; 2. The PGIC score up to 27 weeks; 3. Change in MDS-UPDRS I, II, and III combined and individual scores up to 27 weeks from base-line; 4. Change in Clinical global impression (CGI) - severity of illness score and CGI- Improvement score up to 27 weeks from baseline; 5. Change in Epworth sleepiness scale, Impulsive-compulsive disorders in Parkinson’s dis-ease rating scale up to 27 weeks; 6. Change in Columbia-suicide severity rating scale up to 27 weeks; and 7. Number of participants with treatment-emergent adverse events will be monitored up to 31 weeks.

Pages