Clinical Trial Highlights: Individual Trials

The Clinical Trial 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 Trial Highlights page here.

To search for specific topics, input free text into the search box at the top right of the website. To fine tune the results, put words in quote marks (e.g. "trial" "dyskinesia").

A phase 3, 4-week, multicentre (130 loca-tions), randomized, double-blind, placebo-control-led, parallel-group study of TD-9855 in treating symptomatic neurogenic orthostatic hypotension in subjects with primary autonomic failure

Status: 
Recruiting
Sponsor: 
Theravance Biopharma
Enrollment: 
188
Study Design: 
Participants will be randomized to receive a single oral daily dose of ampreloxetine or placebo. Blinding will be for the investigator, participant, care provider and outcome assessor. There are three phases, a four-week screening, four weeks of randomized treatment and a two week follow up. Apart from the screening visit, the required visits can be conducted either in clinic or remotely.
Rationale: 
The primary outcome measure is the change from baseline in Orthostatic Hyp-otension Symptom Assessment (OHSA) question #1 at week 4. Question #1 assesses dizziness, lightheadedness, feeling faint, or feeling like you might blackout. The timeframe is baseline to week 4. The secondary outcome measures are: 1. Change from baseline in OHSA composite score in weeks 1 to 4 (timeframe: baseline, week 1, week 2, week 3, week 4); 2. Change from baseline in Orthostatic Hypotension Daily Activities Scale (OHDAS) composite score in weeks 1 to 4 (timeframe: baseline, week 1, week 2, week 3, week 4). OHDAS is an assessment of how low blood pressure symptoms affect daily life; 3. Using the Patient Global Impression of Change (PGI-C) scale, a subject rates their total improvement at week 4 compared to baseline; 4. Incidence of patient-reported falls at week 4.

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of K0706 in Subjects With Early Parkinson’s Disease

Status: 
Recruiting
Sponsor: 
Sun Pharma Advanced Research Company Limited
Enrollment: 
504
Study Design: 
This is a Phase 2 multicentre, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety, and tolerability of K0706 among individuals with early PD. The study plans to include dopaminergic drug naïve individuals aged 50 years and above with a clinical diagnosis of probable PD using the MDS clinical diagnostic criteria. The PwP should be projected to not require dopaminergic medications for nine months. Only MAO-B inhibitor usage is allowed at the time of inclusion. Standard exclusionary criteria apply. The drug is administered orally once-daily, and participants will be assigned to one of the three arms: 1. Low dose K0706; 2. High dose K0706; 3. Placebo. The study visits will include at least 1 screening visit, 10 study treatment visits, and 1 follow-up visit 4 weeks post final study visit. The study is being conducted across 79 centers in the USA and Europe.
Rationale: 
The primary outcome measure is the change from baseline in the sum of MDS-UPDRS parts II and III at 40 weeks. The secondary outcome measure will assess the change at 40 weeks from baseline in the following: 1. MDS-UPDRS; 2. Time to initiation of symptomatic treatment; 3. Health-related quality of life as measured by the European quality of life questionnaire 5 lev-el version; 4. Clinician global impression severity; 5. Parkinson’s disease- autonomic questionnaire; 6. Level of K0706. The study will also include other exploratory measures, including effect of the drug on the DaT Scan, Skin biopsy, blood, and CSF levels of K0706. Following exploratory measures will be included: 1. Effect of the active drug on Dopamine Transporter Single Photon Emission Computed Tomog-raphy (DaT SPECT); 2. CSF K0706 levels of progression.
Comments: 
No preclinical data specifically for K0706 or Vodobatinib were found in the literature. According to the company press release, phase 1 studies report a safe profile and CNS presence. We await the efficacy data from the ongoing trial.

A Phase I, Randomized Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Study to Determine the Safety, Tolerability, and Pharmacokinetics (PK) of IkT-148009 in Elderly Subjects

Status: 
Not Yet Recruiting
Sponsor: 
Inhibikase Therapeutics, Inc.
Enrollment: 
112
Study Design: 
This is a phase 1, randomized, placebo-controlled study designed to evaluate the safety, tolerability, and pharmacokinetics of IkT-148009. The study will include elderly, otherwise healthy individuals between the age of 55 to 70 years. The study will have two parts. In part A, single ascending dose, there will be 8 participants in each cohort. Six will receive the investigational drug, and two will receive placebo. Participants will be observed for four days. In part B, cohorts will consist of 12 participants, of which nine will be assigned to the investigational drug. Sentinel dosing will be employed for each cohort, and dose escalation will be undertaken after reviewing the preceding dose’s safety data.
Rationale: 
Primary outcome measures focus on safety and measure vital signs, clinical laboratory data, electrocardiogram, Columbia suicide severity rating scale, adverse events. Pharmacokinetic measurements will include maximum concentration, time to reach maximum concentration and half-life. An exploratory measure will look at the CSF drug concentration for multiple ascending doses.
Comments: 
IkT-148009 is another c-Abl kinase inhibitor being developed as a potential disease-modifying agent for PD. The molecule is still in the early phase and is being evaluated for safety and tolerability at this time. Unlike FB-101, this molecule is being evaluated in elderly otherwise healthy individuals. The study will also assess brain penetrance of the drug by CSF measurement.

A phase 3, 182-week, open-label, multi-center (26 locations) extension study to investigate the safety and tolerability of TD-9855 in treating symptomatic neurogenic orthostatic hypotension (nOH) in subjects with primary autonomic failure

Status: 
Recruiting
Sponsor: 
Theravance Biopharma
Enrollment: 
120
Study Design: 
OAK has three phases, all open label. The first is a 26-week treatment phase, followed by a 156-week treatment extension and ending with a two-week follow up. The study is only open to those participants who complete the REDWOOD trial.
Rationale: 
There are 10 primary outcome measures and no secondary ones, all compared to baseline at week 26: 1. Physical examination - number of subjects with new abnormalities; 2. Neurological examination - number of subjects with new abnormalities; 3. Vital Signs - number of subjects with clinically significant vital sign abnormalities; 4. ECG - number of subjects with clinically significant ECG findings; 5. Clinical laboratory tests - number of subjects with laboratory test abnormalities; 6. Changes in concomitant medications; 7. Adverse events (AEs) - incidence and severity of treatment-emergent adverse events; 8. Subject compliance to study treatment - number of subjects determined to be compliant with study medications; 9. Changes in incidence of falls; 10. Changes from baseline in Columbia Suicide Severity Rating Scale (C-SSRS). The C-SSRS is a tool designed to systematically assess and track suicidal AEs (suicidal behavior and suicidal ideation) and will be used for all visits.
Results: 
Participants in the series of ampreloxetine trials are being recruited in two pathways. The first is SEQUOIA followed by REDWOOD and finishing with OAK. The second is REDWOOD followed byOAK. There will, of course, be dropouts along the way. The inclusion criteria require subjects over the age of 30, diagnosed with nOH and one of PD, MSA or PAF. These criteria are also used to assess de novo entrants to REDWOOD. Exclusion criteria prevent the use of any monoamine oxidase inhibitor (MAOI), which is notable given that MAOI-B inhibitors are very commonly used in PD. Participants in OAK can only come from the REDWOOD trial and must continue to meet the latter’s inclusion criteria. The slightly unusual design of REDWOOD is intended to measure the durability of action of ampreloxetine. Participants are established on active dose for 16 weeks, prior to the six-week blinded phase to assess ampreloxetine against placebo. All of the outcome measures are focused on this phase. Given the scale of the problem with nOH in PD, with a reduced quality of life, and the potential for serious injury from falls, we look forward to the release of data from the SEQUOIA trial shortly after the projected completion date of August 2021.

A phase 3, 22-week, multi-center (61 locations), randomized withdrawal study of TD-9855 in treating symptomatic neurogenic orthostatic hypotension in subjects with primary autonomic failure

Status: 
Recruiting
Sponsor: 
Theravance Biopharma
Enrollment: 
258
Study Design: 
REDWOOD consists of three phases. It starts with 16 weeks of open-label (OL) treatment, then a six-week randomized placebo-controlled treatment phase, and finally a two-week follow-up which is only for patients who do not enroll in OAK, a long-term extension safety study. The blinding for the second phase is quadruple (participant, care provider, investigator, and outcomes assessor). Participants in the SEQUOIA study are eligible to enter REDWOOD. In addition, the trial is recruiting de novo patients.
Rationale: 
The primary outcome measure is the change from baseline in the OHSA question #1 score of one point and worsening of disease severity as assessed by a one-point change in Patient Global Impression of Severity (PGI-S) at week six post randomisation (week 16 to week 22). The secondary outcome measures, all assessed at week six post-randomization (week 16 to week 22), are: 1. Change from baseline in OHSA#1; 2. Change from baseline in OHSA composite score; 3. Change from baseline in OHDAS composite score; 4. Change from baseline in PGI-S; 5. Change from baseline in percent of time spent in standing position as measured by a wearable device that provides date- and time-stamped activity information to measure the time spent in supine, sitting, and standing positions; 6. Change from baseline in average number of steps taken as measured by a wearable device.

A Randomized Double-blind Placebo-controlled Multicenter Study to Assess Safety, Tolerability, Pharmacokinetics and Efficacy of Radotinib in Parkinson’s Disease

Status: 
Not Yet Recruiting
Sponsor: 
II-Yang Pharm. Co. Ltd
Enrollment: 
40
Study Design: 
This is a Phase 2, randomized, parallel assigned, double-blind, placebo-controlled study. The outcome is focused on the safety, tolerability, pharmacokinetics, and efficacy of Radotinib in PwP. The 40 individuals will be randomized to 4 dosing groups. In each dosing group, eight individuals will receive Radotinib, and two will receive matching placebo. The dose will be administered once daily for six months at each escalating dose level. The Radotinib doses being studied include 50mg/day, 100mg/day, 150mg/day and 200mg/day. The data monitoring committee will decide if the individual can be escalated to the next dose level. The study will include dopaminergic drug naïve PwP between 40-80 years of age with Hoehn and Yahr stage of 2.5. They will utilize the MDS clinical diagnostic criteria with a positive DAT scan for inclusion. In addition to standard exclusionary criteria, individuals on certain drugs will be excluded. The comprehensive list of exclusionary drugs includes strong CYP3A4 inhibitors and inducers, P-glycoprotein inducers, and medications that prolong QT interval. The study is being conducted across seven centers in France.
Rationale: 
The primary outcome measure focuses on safety assessment by measuring the incidence and severity of adverse events 12 months after dose administration. The secondary outcome measures assess the effect in two main domains, pharmacokinetic and clinical. 1. Pharmacokinetic assessments will be done at 14 days after dose administration, and meas-urements include peak observed drug concentration, time to reach peak drug concen-tration, trough plasma concentration, the area under plasma concentration-time curve, elimination half-life, apparent total drug clearance, and apparent volume distribution; 2. Clinical assessment will include: a. Change in MDS-UPDRS parts I-III at 6 months; b. Time to initiation of dopamine replacement therapy assessed at 6 months; c. Patient reported outcome will include a change in the quality of life via PDQ-39 and the subject’s clinical global impression scale at 12 months. Other outcome measures will include the following: a. Change in Brain DaT SPECT scan; b. CSF concentration of the following at 6 months: alpha-synuclein, Tau, phospho-Tau (p-181), beta-amyloid peptide 1-42; c. CSF and plasma concentration of Radotinib; d. Serum concentration of NF-L.
Comments: 
Radotinib is a potential c-Abl inhibitor alternative drug for PD owing to its superior brain penetration [2,3]. The current study is exploring doses lower than the approved dose for CML. Compared to other kinase inhibitors, Radotinib exerts its effect via c-Abl inhibition only [3]. It is undetermined whether the road to effective alpha-synuclein reduction is via multiple or selective kinase inhibition. While there is conflicting preclinical data regarding Radotinib efficacy, whether this translates to human efficacy is yet to be seen.

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 (REASON).

Status: 
Recruiting
Sponsor: 
Biogen
Enrollment: 
82
Study Design: 
The study is double-blind, randomized, placebo-controlled, sequential allocation, and multicenter at 16 sites in the USA, Canada, Israel, Norway, Spain, and the UK. The age range for recruitment is between 35 and 80. Patients must be less than seven years since diagnosis, have an H&Y score of 3, and be free of major motor fluctuations or dyskinesia. Standard exclusionary criteria apply. The single ascending dose (SAD) is evaluating six dose levels of BIIB094, and the multiple ascending dose (MAD) will test three dose levels. The study is planned to complete in September 2023.
Rationale: 
There are one primary and six secondary outcome measures. The primary one is the number of participants with adverse events (AEs) and serious adverse events (SAEs). The SAD will be conducted from screening (day -42) up to day 85. The MAD will run from screening (day -77) up to day 253. Secondary outcomes are: 1. Serum concentrations of BIIB094; 2. Area under the concentration-time curve from time zero extrapolated to infinity (AUCinf); 3. Area under the concentration-time curve from time zero to last quantifiable concentration (AUClast); 4. Maximum concentration (Cmax); 5. Time to reach maximum concentration (Tmax); 6. Terminal elimination half-life (t1/2). The timeframe for each of the secondary outcomes for the SAD is pre-dose through day 57; and for the MAD, pre-dose through day 169.
Comments: 
BIIB094 is the first ASO drug to reach the clinical phase of development for PD. The ultimate goal is to attempt to modify the course of PD, slowing or even stopping the progression. Establishing safety and tolerability parameters with a relatively new technology are thus crucial.

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral FB-101 in Healthy Subjects

Status: 
Recruiting
Sponsor: 
1st Biotherapeutics, Inc.
Enrollment: 
48
Study Design: 
This is a Phase 1, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetics of the active drug, FB-101. The study has two parts where the drug will be administered in single and multiple ascending doses. 48 healthy adults aged between 19 to 55 years will be included. Standard inclusion and exclusionary criteria apply. The study is being conducted in Baltimore, USA.
Rationale: 
The primary outcome measures the number and severity of treatment-emergent adverse events seven days after the last dose. The secondary outcome will measure the peak plasma concentration and area under the curve of FB-101.
Comments: 
FB-101 is another c-Abl kinase inhibitor being introduced to the gamut of kinase inhibitors. There is a lack of available preclinical data at this time. The molecule is still in the early stages. The current study is a phase 1 trial in younger healthy volunteers with no assessment of BBB penetrance. Safety, tolerability, and efficacy in the PD population are yet to be explored. The study is listed to have been completed in June 2020, but no updates have been provided on clinicaltrials.gov or the company website. The delay could have been in the setting of the COVID-19 pandemic. Further news and data are awaited.

A phase 1, randomized, placebo-controlled, double-blind study to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of DNL151 in healthy volunteers.

Status: 
Recruiting
Sponsor: 
Denali Therapeutics Inc.
Enrollment: 
200
Study Design: 
The study is a double-blind, randomized, placebo-controlled, single ascending dose (SAD), multiple ascending dose (MAD), and 28-day safety study in healthy volunteers.
Rationale: 
Outcome Measures: There are seven primary and two secondary outcome measures. The primary ones are: 1. Incidence of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) and discontinuations due to TEAEs; 2. Maximum observed concentration (Cmax) in plasma; 3. Time to maximum observed concentration (Tmax) in plasma; 4. The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) in plasma (SAD only); 5. Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUC [0-last]) in plasma; 6. The area under the concentration-time curve over a dosing interval (AUC0-T) in plasma (MAD only); 7. Apparent terminal elimination half-life (t1/2) in plasma. The timeframe for the measures above is up to 42 days. Secondary outcome measures are the concentration of DNL151 in CSF (following selected single and multiple doses) up to 13 days from initiation; and the pharmacodynamics of DNL151 in whole blood as measured by the percent change from baseline in pS935, up to 42 days.
Comments: 
This study is a large, classic design phase 1 safety study in healthy volunteers. Inclusion and exclusion criteria are straightforward. The trial has been conducted in parallel with a phase 1b in 25 PwP (NCT04056689), producing data to support progression into the next phase.

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.

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