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").

Buspirone, in Combination With Amantadine, for the Treatment of Levodopa-induced Dyskinesia

Status: 
Recruiting
Clinicaltrials.gov identifier: 
NCT02589340
Sponsor: 
Oregon Health and Science University
Enrollment: 
15
Study Design: 
This is a phase 1, single-center, double-blinded, randomized, placebo-controlled, two-period cross-over study designed to assess the safety, tolerability, and efficacy of combination therapy of buspirone and amantadine on dyskinesia. They are enrolling PD participants between 18 to 99 years of age on a stable medication regimen. Participants should have mild to severe dyskinesia and should be on amantadine (200-500mg/day) with insufficient control. Standard exclusionary criteria are applied. This study will not include participants with DBS. Included participants will be randomized to one of the two study arms. Arm 1: Buspirone titrated up over the course of 2 weeks to reach 30mg/day for a week. Arm 2: Placebo titrated up to match arm 1. Participants will be crossed over the treatment sequence. Monitoring is done every 2 weeks for safety, tolerance, compliance and dyskinesia assessment.
Rationale: 
The primary outcome measure will assess the: 1. Area under the curve – measurements for dyskinesia for a 6-hr levodopa dose cycle; 2. Change in UdysRS up to 6 weeks; 3. Safety and tolerability assessment by monitoring adverse events for up to 6 weeks. No secondary outcomes have been specified.
Comments: 
None.

A Phase 1/2 Study of Intra-putaminal Infusion of Adeno-Associated Virus Encoding Human Aromatic L-Amino Acid Decarboxylase in Subjects with Parkinson’s Disease

Status: 
Recruiting
Clinicaltrials.gov identifier: 
NCT02418598
Sponsor: 
Jichi Medical University
Enrollment: 
6
Study Design: 
This study is a phase 1/2 non-randomized, single center, open label, interventional, safety and dose evaluation study of the active agent AAV-hAADC-2 being delivered intra-putaminal via stereotaxic surgery. It is being conducted at the Jichi Medical University in Japan. The target putamen is identified on the pre-operative MRI brain and then bilateral putamina are infused with the active drug at a total of 4 spots (2 on each putamen). AAV-hAADC-2 is administered via bilateral intra-putaminal infusion in either low or high dose. There are two sequential study arms. Cohort 1 receives low dose (3x1011 vector genome/subject) and is infused with a total volume of 200 μl of the drug (50 μl per site). If there are no safety concerns at 6 months, then the study moves to cohort 2. Cohort 2 will receive high dose (9x1011 vector genome/subject) with 600 μl of total infusion volume (150 μl per site). The study includes patients with clinical diagnosis of idiopathic PD aged between 35 to 75 years of age with no other known or suspected cause of parkinsonism. Patients should be levodopa responsive and should have been on it for at least 5 years. An OFF state MDS-UPDRS score between 30–100 and Hoehn and Yahr stage IV is required. Patients with a history of 3 hours or more of intensive or violent dyskinesia are excluded from the study. Standard surgical exclusionary criteria are applied.
Rationale: 
Primary outcome measures include assessment of safety of intra-putaminal infusion of AAV-hAADC-2 as measured by adverse events. Secondary outcomes include two measures: 1. The treatment effect of the drug at the end of 6 months. This is assessed by improvement in PD symptoms as recorded in subject diaries, clinical assessment and change in levodopa dosage. 2. The amount of intra-putaminal expression of AAV-hAADC-2 after 6 months, as measured by FMT-PET imaging. Investigators will continue to assess the safety for 5 years after baseline examination and long term follow up will continue for 10 years.
Comments: 
This is a phase 1/2 dose escalation safety and efficacy study. No results have been published yet.

VY-AADC02 for Parkinson’s Disease with motor fluctuations

Status: 
Recruiting
Clinicaltrials.gov identifier: 
NCT03562494
Sponsor: 
Voyager Therapeutics
Enrollment: 
42
Study Design: 
Voyager’s phase 2 study is randomized, placebo-controlled and double-blind, comparing one active dose of VY-AADC02 with a placebo of sham surgery involving a partial burr/twist hole without dura penetration.
Rationale: 
Primary outcomes will measure both efficacy and safety. The safety criteria will be evaluated at 12 months and 30 day follow up. The efficacy measures will be taken at 12 months, with enzyme activity also assessed at 45 days. The outcome measures are: a. change in patient rated motor fluctuations; b. percent coverage within the putamen at time of administration of VY-AADC02; c. change in AADC enzyme activity (distribution); d. safety of VY-AADC02 as measured by: i. number of treatment emergent adverse events, ii. changes in vital signs, iii. physical examinations and routine clinical laboratory analysis, (hematology and clinical chemistry), iv. changes in findings on brain images, v. the Columbia-Suicide Severity Rating Scale (C-SSRS), vi. change in impulse control disorders. Secondary outcomes are all related to efficacy, as measured at the twelve-month timepoint by changes in: a. activities of daily living (UPDRS II); b. PD related quality of life (PDQ-39); c. time course response to levodopa (UPDRS III); d. clinical global function (CGI); e. overall non-motor symptoms (NMSS).
Comments: 
Voyager are recruiting patients at least four years since diagnosis, although there is no explicit requirement for the presence of motor complications, despite the study title. The choice of primary and secondary outcome measures has some interesting features. The primary efficacy outcome is a patient rating of motor fluctuations, with UPDRS measures only as secondary outcomes. The assessment of coverage of the putamen on administration and distribution of enzyme activity, both already validated in the phase 1b trial, will give a good indication of target engagement and change in biological activity. The combination of a good safety profile thus far; the change in biological activity leading to significant clinical change; and a favourable regulatory review, give cause for optimism with VY-AADC02.

Study of OXB-102 (AXO-Lenti-PD) in patients with idiopathic Parkinson’s Disease (SUNRISE-PD)

Status: 
Recruiting
Clinicaltrials.gov identifier: 
NCT03720418
Sponsor: 
Axovant
Enrollment: 
32
Study Design: 
There are two parts to this phase 1/2 study. The first is an open-label phase where three escalating dose levels will be tested. The second phase will take the optimal dose from part one into a randomized, double-blind phase in which patients will receive either active AXO-Lenti-PD or an imitation surgical procedure (ISP).
Rationale: 
Primary outcomes are all related to safety at the three-month time point, as measured by: a. incidence of treatment emergent adverse events and serious adverse events; b. changes in clinical laboratory analysis; c. changes in vital signs; d. changes in brain MRI findings; e. changes in physical examination. Secondary outcomes are all related to efficacy, as measured at the six-month timepoint by changes in: a. the Unified Parkinson’s Disease Rating Scale (UPDRS) scores compared to baseline in defined “OFF” and “ON” medication states; b. motor fluctuations compared to baseline as assessed by patient diaries; c. the dyskinesia rating scale from baseline.
Comments: 
Axovant are recruiting patients at a relatively advanced stage of Parkinson’s, with at least five years since diagnosis and a Hoehn and Yahr stage of 3 or 4 in the OFF state. The patients must also be experiencing motor complications. Results from the first cohort using the lowest dose of AXO-Lenti-PD in two patients, were announced in March 2019 [3], showing efficacy greater than the highest dose of ProSavin® used in previous studies. No serious adverse events were reported. Clearly, caution must be applied given the number of patients and further results are awaited.

A Phase 1 Open-Label Dose Escalation Safety Study of Convection Enhanced Delivery (CED) of Adeno-Associated Virus Encoding Glial Cell Line-Derived Neurotrophic Factor (AAV2-GDNF) in Subjects with Advanced Parkinson’s Disease

Status: 
Active, No Longer Recruiting
Clinicaltrials.gov identifier: 
NCT01621581
Sponsor: 
National Institute of Neurological Disorders and Stroke (NINDS)
Enrollment: 
25
Study Design: 
This is a phase 1 single center, open-label, dose escalation, safety and tolerability study of the AAV2-GDNF (adeno-associated virus, serotype 2 containing the human GDNF complementary DNA). The active drug will be delivered surgically by convection-enhanced delivery to bilateral putamina. The study includes 4 cohorts to evaluate the four escalating dose levels. Each cohort will have 6 subjects. The drug level for each cohort is as follows: Cohort 1: 9 x 10 sup.10 vg; Cohort 2: 3 x 10 sup.11 vg; Cohort 3: 9 x 10 sup.11 vg; Cohort 4: 3 x 10 sup.12 vg. The study includes individuals 18 years and above with clinical idiopathic PD of at least 5 years disease duration with no other known or suspected cause for parkinsonism. An Off state UPDRS score of more than or equal to 30 and Hoehn and Yahr stage of III and IV are required for inclusion. The study also requires a 30% or greater improvement in the UPDRS total motor score on sinemet study according to the CAPSIT guidelines. The participants in the study will be followed for 5 years with 18 outpatient study visits and a 3-day stay in the hospital post-surgery. Lumbar puncture for CSF analysis will be done at the time of surgery, 6 months and 18 months after surgery.
Rationale: 
Primary outcome measure: To assess the safety and tolerability of 4 different dose levels of AAV2-GDNF over a period of 12 years. Secondary outcome measures: To obtain preliminary data regarding the potential for clinical responses of the 4 dose levels testing by assessing the magnitude and variability of any treatment effects including clinical, laboratory and neuroimaging studies.
Comments: 
GDNF and neurturin have been studied extensively as potential neuroprotective interventions in PD so far with disappointing results despite reproducibly positive data in preclinical models. It remains to be determined if lack of success in PD clinical trials reflects a lack of biological effect of intervention, limitations of the technical delivery modes (insufficient coverage of putamen, dose, etc) or failure to reverse the course of the advanced disease at the time of intervention. The ongoing study will be closely followed.

A Study to Assess the Safety and Efficacy of the Gastric-retentive AP-CD/LD in Advanced Parkinson’s Patients (Accordance)

Status: 
Active, No Longer Recruiting
Clinicaltrials.gov identifier: 
NCT02605434
Sponsor: 
Intec Pharma
Enrollment: 
420
Study Design: 
The phase 3 Accordance study is a multi-center (97 study locations), global, randomized, double-blind, double-dummy, active-controlled, parallel-group study in adult subjects with fluctuating PD. The study will have 2 open label titration periods of 6 weeks each prior to the double-blind maintenance period. In the open label periods, all patients will be stabilized on the active comparator, IR-CD/LD and then on AP-CD/LD. The double-blind maintenance period will be 13 weeks long.
Rationale: 
The primary outcome is change from baseline through to study completion, an average of 27 weeks, in the percentage of daily “Off time” during waking hours, based on Hauser Home Diary assessments. Secondary outcomes, all measured on the same timescale as the primary outcome, are: 1. Change in “On time” without troublesome dyskinesia during waking hours; 2. Change in the number of total daily LD doses; 3. Clinical Global Impression Improvement (CGI-I), as recorded by physician & patient; 4. Change in total UPDRS Score (sum of Parts I-III).
Comments: 
Until disease-modifying therapies are available, people with Parkinson’s will welcome any therapy that extends the duration of symptom relief and reduces motor fluctuations. The novel design of the Accordion Pill and the promising safety and efficacy data generated in phases 1 and 2, hold out great hope for the achievement of these benefits.

A study to evaluate the efficacy of Prasinezumab (RO7046015/PRX002) in participants with early Parkinson’s Disease (PASADENA)

Status: 
No Longer Recruiting, Ongoing
Clinicaltrials.gov identifier: 
NCT03100149
Sponsor: 
Hoffmann-La Roche
Enrollment: 
300
Study Design: 
The PASADENA study has two parts, both of which are randomized, double-blind and placebo controlled. The first part has three arms: ARM 1 – high dose Prasinezumab 4500mg for participants with body-weight greater than or equal to (>/=) 65kg or 3500 mg for participants with body-weight less than (<) 65 kg; ARM 2 – low dose Prasinezumab 1500mg; ARM 3 – placebo. All three arms will receive the relevant dose through IV infusion every 4 weeks for 52 weeks. At the end of part 1, patients who have been on placebo will be randomized to either high dose or low dose Prasinezumab, joining those patients who have already been on the high or low dose. Part 2 will therefore have 2 arms: HIGH DOSE ARM - high dose group participants and placebo group participants randomized to high dose level will receive Prasinezumab at high dose level as intravenous infusion every 4 weeks for additional 52 weeks; LOW DOSE ARM - low dose group participants and placebo group participants randomized to low dose level will receive Prasinezumab at low dose level as intravenous infusion every 4 weeks for additional 52 weeks.
Rationale: 
Primary Outcome Measures: 1. Change From Baseline in Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 52 [Time Frame: Baseline and Week 52]. Secondary Outcome Measures: 1. Change From Baseline in Dopamine Transporter Imaging With Single Photon Emission Computed Tomography (DaT-SPECT) Signal at Week 52 [Time Frame: Baseline and Week 52]. 2. Change From Baseline in the MDS-UPDRS Motor Subscale (Part III) Score [Time Frame: Baseline and Week 52]. 3. Clinical Global Impression of Improvement (CGI-I) Score at Weeks 24 and 52 [Time Frame: Week 24 and Week 52]. 4. Patient Global Impression of Change (PGIC) Score at Weeks 24 and 52 [Time Frame: Week 24 and Week 52]. 5. Time to Start of Dopaminergic Symptomatic Treatment [Time Frame: From Baseline to Week 52]. 6. Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) [Time Frame: From Day 1 to Week 104]. 7. Percentage of Participants With Anti-Drug Antibodies (ADAs) Against RO7046015 [Time Frame: Baseline, Pre-dose (0 hours) on Weeks 4, 20, 36, 52, 56, 68, 80, and 104; at early termination (up to Week 104), and follow-up (12 weeks after last dose up to Week 116)]. 8. Systemic Clearance (CL) of RO7046015 [ Time Frame: Predose (0 hours) and end of infusion (infusion length=2 hours or less) on Day 1, Weeks 4, 20, 36, 52, 56, 68, 80, and 104; at Day 7, Day 14, early termination (up to Week 104), and follow-up (12 weeks after last dose up to Week 116)]. 9. Apparent Volume of Distribution (Vz/F) of RO7046015 [Time Frame: Predose (0 hours) and end of infusion (infusion length=2 hours or less) on Day 1, Weeks 4, 20, 36, 52, 56, 68, 80, and 104; at Day 7, Day 14, early termination (up to Week 104), and follow-up (12 weeks after last dose up to Week 116)]. 10. Area Under the Serum Concentration-Time Curve (AUC) of RO7046015 [Time Frame: Predose (0 hours) and end of infusion (infusion length=2 hours or less) on Day 1, Weeks 4, 20, 36, 52, 56, 68, 80, and 104; at Day 7, Day 14, early termination (up to Week 104), and follow-up (12 weeks after last dose up to Week 116)]. 11. Maximum Observed Serum Concentration (Cmax) of RO7046015 [Time Frame: Predose (0 hours) and end of infusion (infusion length=2 hours or less) on Day 1, Weeks 4, 20, 36, 52, 56, 68, 80, and 104; at Day 7, Day 14, early termination (up to Week 104), and follow-up (12 weeks after last dose up to Week 116)]. 12. Minimum Observed Serum Trough Concentration (Ctrough) of RO7046015 [Time Frame: Predose (0 hours) and end of infusion (infusion length=2 hours or less) on Day 1, Weeks 4, 20, 36, 52, 56, 68, 80, and 104; at Day 7, Day 14, early termination (up to Week 104), and follow-up (12 weeks after last dose up to Week 116)].
Comments: 
This is a comprehensive phase 2 study assessing both efficacy and safety/tolerability at two active dose levels of Prasinezumab.

Nilotinib in Parkinson’s Disease (NILO-PD)

Status: 
No Longer Recruiting
Clinicaltrials.gov identifier: 
NCT03205488
Sponsor: 
Northwestern University / Michael J Fox Foundation (MJFF)
Enrollment: 
75
Study Design: 
Out of 75 participants that will be recruited and randomly assigned 1:1:1 to the 3 groups (arms), 150mg: 300mg: placebo; all once daily. Intervention duration: 6 months and 2 months follow up (NCT03205488) and 12 months and 3 months follow up (NCT02954978).
Rationale: 
PRIMARY OUTCOME MEASURE: Safety and tolerability (both studies). SECONDARY OUTCOME MEASURES: Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III (motor function) will be evaluated to determine if Nilotinib has the potential to reduce the MDS-UPDRS motor score as well as a spectrum of motor and non-motor outcome scales, PK profile in cerebrospinal fluid and a number of exploratory biomarkers.
Comments: 
Nilotinib is a drug approved for treatment of chronic leukaemia and as such has a number of safety concerns. The current studies aim to assess safety/ tolerability of nilotinib as well as explore signals of efficacy to determine if the future studies are warranted. There are other molecules targeting the c-ABL pathway in development with potentially better safety profile and better CNS penetration, (Sun Pharma, NCT02970019).

Impact of Nilotinib on Safety, Tolerability, Pharmacokinetics and Biomarkers in Parkinson’s Disease (PD Nilotinib)

Status: 
No Longer Recruiting
Clinicaltrials.gov identifier: 
NCT02954978
Sponsor: 
Georgetown University
Enrollment: 
75
Study Design: 
Out of 75 participants that will be recruited and randomly assigned 1:1:1 to the 3 groups (arms), 150mg: 300mg: placebo; all once daily. Intervention duration: 6 months and 2 months follow up (NCT03205488) and 12 months and 3 months follow up (NCT02954978).
Rationale: 
PRIMARY OUTCOME MEASURE: Safety and tolerability (both studies). SECONDARY OUTCOME MEASURES: Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III (motor function) will be evaluated to determine if Nilotinib has the potential to reduce the MDS-UPDRS motor score as well as a spectrum of motor and non-motor outcome scales, PK profile in cerebrospinal fluid and a number of exploratory biomarkers.
Comments: 
Nilotinib is a drug approved for treatment of chronic leukaemia and as such has a number of safety concerns. The current studies aim to assess safety/ tolerability of nilotinib as well as explore signals of efficacy to determine if the future studies are warranted. There are other molecules targeting the c-ABL pathway in development with potentially better safety profile and better CNS penetration, (Sun Pharma, NCT02970019).

A Phase 1, Randomized, Double-Blind, Single Ascending Dose Trial of the Safety, Tolerability and Pharmacokinetics of NPT200-11 in Healthy Subjects

Status: 
Completed
Clinicaltrials.gov identifier: 
NCT02606682
Sponsor: 
Neuropore Therapies/UCB
Enrollment: 
55
Study Design: 
Single ascending dose of orally administered capsule(s) NPT200-11 vs placebo: 15, 30, 60,120, 240, 360 and 480 mg dose.
Rationale: 
PRIMARY OUTCOME MEASURE: Safety, including adverse events, physical examinations, ECGs, clinical laboratory tests. Time Frame: Screening (28 days prior to dosing) through Day 7. SECONDARY OUTCOME MEASURES: To possibly determine the maximally tolerated dose (MTD) of orally administered NPT200-11 in healthy subjects. The number of participants with unacceptable toxicities at each dose level will determine the maximally tolerated dose.
Comments: 
An early phase SAD study was completed but the data have not been published and no information on future drug development are available.

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