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.

Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of 36 Weeks of Treatment With NLY01 in Early-Stage Parkinson’s Disease

Status: 
Recruiting
Sponsor: 
Neuraly, Inc.
Enrollment: 
240
Study Design: 
This is a Phase 2 randomized, placebo-controlled double-blind study comparing three parallel assigned arms: NLY01 2.5mg injection, NLY01 5mg injection, and placebo saline injection. Subjects will be randomized 1:1:1 to these three arms. The drug or placebo is delivered via weekly subcutaneous injection. The study includes individuals aged 30 to 80 with a diagnosis of Parkinson’s disease within 5 years prior to screening. Additionally, participants complete a DaTScan which must be consistent with a PD diagnosis. Notably, individuals who have used dopaminergic treatment or MAO-B inhibitors for more than 28 days, or who have had previous surgical treatment, are excluded from participation in the study. Those found to have major depression or suicidal ideation within 1 year of screening will be excluded.
Rationale: 
In addition to the primary outcomes of safety and tolerability, the study is assessing efficacy as measured by change from baseline to 36 weeks in the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts II and III combined score, for each dose of NYL01 compared to placebo. MDS-UPDRS Part II assesses motor aspects of daily living, and Part III assesses motor signs of Parkinson’s. Secondary efficacy endpoints include change from baseline in: UPDRS Part I: Non-Motor Aspects of Experiences of Daily Living; Clinical Global Impression Scale–Severity (CGI-S); Patient Global Impression of Severity (PGI-S); Schwab and England Activities of Daily Living Scale (SE-ADL); Parkinson’s Disease Questionnaire–39 (PDQ-39); Montreal Cognitive Assessment (MoCA); Scales for Outcomes of Parkinson’s Disease Cognition (SCOPA-COG); Non-Motor Symptoms Scale (NMSS). Other Secondary Assessments include change from baseline in: DaTscan (quantitative); Incidence of anti-NLY01 antibodies; NLY01 population PK assessment. Safety and Tolerability Assessments include: Incidence, severity, and duration of all reported treatment-emergent adverse events (TEAEs); Vital signs, physical examinations, and ECGs; Clinical laboratory assessments; Columbia-Suicide Severity Rating Scale (C-SSRS); Epworth Sleepiness Scale (ESS); Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease–Rating Scale (QUIP-RS); Beck Depression Inventory–II (BDI-II).
Comments: 
The unique quality of NYL01 as a pegylated version of the previously-studied exenatide confers a potential advantage over the more well-known compound. By increasing blood-brain-barrier penetration with pegylation, NYL01 may have increased target engagement of central GLP-1 receptors, which in turn could prove more efficacious than its un-pegylated counterpart. This would be an additional benefit to the anticipated well-tolerated safety profile, given the robust safety data for existing GLP-1 agonists.

GLP1R in Parkinson’s Disease (GIPD)

Status: 
Not Yet Recruiting
Sponsor: 
Oslo University Hospital
Enrollment: 
120
Study Design: 
The study is a double-blind, placebo-controlled, randomised 1:1, crossover, delayed start design, run in a single centre. Treatment in the first stage lasts for 2 years. This is followed by an open second stage where all participants will be on semaglutide, with treatment lasting for a further 2 years.
Rationale: 
The primary outcome measure is motor function as measured by MDS-UPDRS part 3 in the OFF state at baseline and 48 months. There are no official secondary outcomes specified, although the text describes further parameters that will be assessed: a. Motor function measured by levodopa equivalent dose (LED); b. Nigrostriatal degeneration measured by changes in DATscan; c. Cognitive function measured by MME and MOCA; d. Quality of life measured by EQFDQ and PDQ; e. Non-motor symptoms measured by NMSS; f. Inflammatory markers measured in blood and CSF. Each of the above will be measured at baseline, 12, 24, 36 and 48 months. In addition, the blood and CSF samples will be used to assess the permeability of the blood brain barrier to semaglutide.
Comments: 
The target population for this trial is patients newly diagnosed with PD, confirmed by DaTscan. Enrolment must happen within a year of diagnosis. The eligible age range is 40-75, narrower than many other PD trials. Ozempic is available in 2 doses, 0.5mg and 1.0mg; the Oslo PD study will test the higher dose. Given the comparatively slow degeneration rate in PD, the treatment periods of 2 years each are a positive feature of this study. Assuming no other confounding factors, the first 2-year block should reach enough decline in the placebo group to enable a meaningful comparison with the active drug. Semaglutide is the first GLP-1 agonist to be taken orally. This could be a strong competitive edge if the efficacy of GLP-1 agonists in PD should prove to be a class effect with similar outcomes.

Effect of Exenatide on disease progression in early Parkinson’s Disease.

Status: 
Recruiting
Sponsor: 
Stockholm Health Care Services
Enrollment: 
60
Study Design: 
The study is single-centre, double-blind, parallel group, randomised and placebo-controlled. The exenatide and placebo groups will receive treatment for 18 months, with the final evaluation occurring 3 months afterwards.
Rationale: 
The primary outcome measure is FDG-PET analysis at baseline, 9 and 21 months. Secondary outcomes are: a. MDS-UPDRS part 3 in OFF-medication state, and accelerometer-based parameters of physical activity at baseline, 9, 18 and 21 months; b. MDS-UPDRS parts 1, 2, 3, and 4 in the ON-medication state, Hoehn and Yahr stage, levodopa equivalent daily dose, CSF and plasma parameters at baseline, 3, 6, 9, 12, 15, 18, and 21 months; c. PDQ-39, NMSQuest, ESS, MADRS at baseline, 6, 12, 19 months; d. MoCA at baseline, 9, and 21 months; e. B-SIT at baseline, 9, and 18 months.
Comments: 
The target patient population for this study is those PwP in the early stages of PD, as defined by a Hoehn and Yahr score of 2 in the ON state, currently on levodopa therapy. A 3-month washout period at the end of the treatment phase is intended to minimise any symptomatic relief potentially provided by exenatide. This study will provide analysis of changes in brain metabolism that will provide further insight to the mechanism of action of GLP-1 agonists in PD progression. In addition, it will produce further data on the clinical effect of exenatide in PD.

SR-Exenatide (PT320) to Evaluate Efficacy and Safety in Patients With Early Parkinson’s Disease

Status: 
Recruiting
Sponsor: 
Peptron Inc.
Enrollment: 
99
Study Design: 
This is a multi-centre (3 locations) randomised, double-blind, placebo-controlled, parallel group study. There are 3 arms – placebo; PT320 2.0mg once weekly; and PT320 2.5mg every 2 weeks with placebo administered every other week.
Rationale: 
The primary outcome measure is motor function as measured by MDS-UPDRS part 3 at baseline and 48 weeks. Secondary outcome measures are: 1. Specific to non-specific binding ratio (SNBR) by PET scan at baseline and 48 weeks; 2. MDS-UPDRS part 3 score at 0, 24 and 60 weeks; 3. MDS-UPDRS parts 1,2 and 4 at baseline, 24,48 and 60 weeks; 4. Korean PD Questionnaire-39 at 0, 48 and 60 weeks; 5. Montreal cognitive assessment-Korean (MoCA-K) at baseline, 24,48 and 60 weeks; 6. Korean-non-motor symptoms scale (K-NMSS) at baseline, 24,48 and 60 weeks; 7. The percentage of subjects in each modified Hoehn and Yahr stage at baseline, 24,48 and 60 weeks; 8. Change in levodopa dosage at baseline, 2, 4, 8, 12, 24, 36, 48 and 60 weeks. This outcome measure is the starting time of levodopa treatment and the percentage of subjects taking levodopa. The study will also measure pharmacokinetic parameters in plasma and CSF, together with anti-exenatide antibodies, at baseline, 2, 12, 24, 36, 48 and 60 weeks.
Comments: 
The inclusion criteria are for PwP between the ages of 40 and 75 diagnosed in the previous 2 years. They may already be on dopaminergic therapy (less than 600mg levodopa per day) or not yet have started. The Hoehn and Yahr stage must be <2.5. The Bydureon formulation of exenatide is already a sustained release product, enabling weekly dosing. The Peptron product will need to prove superiority in efficacy, or sufficiently better convenience, to be clinically competitive.

Exenatide Once Weekly Over 2 Years as a Potential Disease Modifying Treatment for Parkinson’s Disease (Exenatide-PD3)

Status: 
Not Yet Recruiting
Sponsor: 
University College London
Enrollment: 
200
Study Design: 
A randomised, double-blind, placebo-controlled, parallel group study run at a single centre. The active drug is a 2mg, self-administered, sub-cutaneous injection with a 2-year treatment period.
Rationale: 
The primary outcome measure is change in the motor function as measured by MDS-UPDRS part 3 in the OFF state between baseline and 96 weeks. Secondary outcome measures are: 1. MDS-UPDRS parts 1,2 and 4 in the ON state; 2. Timed walk assessment both ON and OFF; 3. Montreal cognitive assessment (MOCA); 4. Unified dyskinesia rating scale (UDysRS); 5. Patient health questionnaire-9 (PHQ-9); 6. PD quality of life (PDQ-39); 7. Non-motor symptoms scale (NMSS); 8. Levodopa equivalent dose (LED); 9. Hauser diary (3 day) of PD state; 10. Safety and tolerability. These assessments will also be done at baseline and 96 weeks.
Comments: 
The inclusion criteria are for PwP between the ages of 25 and 80 who are already on dopaminergic therapy. The Hoehn and Yahr stage must be <2.5 in the ON state, thus excluding more advanced patients. Given the comparatively slow degeneration rate in PD, the treatment period of almost 2 years is a positive feature of this study. The success of the trial does, however, assume that the same rate of increase in UPDRS scores in the placebo group seen in the 48-week period in the previous studies will continue over 96 weeks in this one. This study should also show whether the positive impact of exenatide treatment on MDS-UPDRS scores seen in prior work is a short-lived effect that dissipates with time, simply delaying a return to an expected rate of decline; or if the extended treatment may slow a further decline in disability, thus meeting the real need for people with PD, a medicine that slows the progressive development of symptoms.

Effects of Exenatide on Motor Function and the Brain

Status: 
Recruiting
Sponsor: 
University of Florida
Enrollment: 
15
Study Design: 
This is a single center, open-label, single group assignment study. All participants will receive the intervention of exenatide 2mg, administered as a weekly subcutaneous injection for the 1-year duration of the study. Eligible participants are aged 40 to 77 with a diagnosis of PD within 5 years of screening and Hoehn and Yahr stage less than or equal to 2. Main exclusion criteria include individuals with previous exposure to exenatide, diagnosis of Diabetes, renal failure, “psychiatric disorders” or dementia defined as MoCA < 23. Because of the MRI imaging obtained during the study, individuals with any implantable electrical device or metallic hardware, or with significant claustrophobia, are excluded.
Rationale: 
This study’s Primary Outcome Measures are changes in four functional and structural MRI brain imaging metrics from baseline to the study end at 1 year. The four metrics being measured include: 1) free-water accumulation in the substantia nigra, 2) blood oxygen level-dependent (BOLD) signal in the posterior putamen, 3) BOLD signal in the primary motor cortex (M1), 4) BOLD signal in the supplemental motor area (SMA). Additional measures include questionnaires regarding quality of life and depression, motor and strength function tests and cognitive tests.
Comments: 
This study is unique in that it is a single-center open-label study of exenatide with only one treatment arm and no placebo arm. The lack of a placebo group for comparison of MRI metric changes from baseline to 1-year may limit the study’s ability to formulate conclusions of exenatide’s effect on brain structure and function, though it is unclear if the study team plans to compare the treatment group to pre-existing control MRIs. The small sample size also has the potential to be a constraint in finding significance of the study’s outcomes. The fact that this study’s primary outcome is change in MRI imaging measures sets it apart from concurrent GLP-1 agonist trials.

Multicenter, Randomized, Placebo-controlled, Double Blinded, Parallel Arm Proof-of-concept Trial of Lixisenatide in Patients With Early Parkinson’s Disease

Status: 
Recruiting
Sponsor: 
University Hospital, Toulouse
Enrollment: 
158
Study Design: 
This is a multi-center randomized double-blind placebo-controlled proof-of-concept Phase 2 trial. It is a 2-arm study, with participants randomized 1:1 to either lixisenatide or placebo. The Lixisenatide group will receive lixisenatide 10μg/day for 14 days and then 20μg/day, administered via once-daily subcutaneous injections for 12 months. Participants unable to tolerate the 20μg/day dose can have their dose reduced to 10μg/day. After 12 months of treatment period there will be a 2-month wash-out period. The study includes individuals aged 40 to 75 years who have early-stage PD, defined as PD diagnosis for less than 3 years without dyskinesias or motor fluctuations. Participants must have an optimized and stable PD medication regimen, including dopamine agonist, levodopa, and/or MAO B-inhibitor) for one month prior to the baseline study assessment. Participants are expected to remain on their medication regimen for at least the first 6 months, and ideally the full 12 months, of the study. Notably, individuals will be excluded from participation if they have had previous GLP-1 agonist exposure, have participated in another interventional trial within 30 days, or have had surgical intervention for Parkinson’s. Medical conditions that prevent participation include major depression, cognitive impairment (MoCA score <26), Type 1 or 2 Diabetes, have had a weight change more than 5kg in 3 months prior to screening, hyperthyroidism or uncontrolled hypothyroidism.
Rationale: 
The Primary Outcome Measure is the change from baseline to end-point (month 12) in the MDS-UPDRS Part III motor sub-score, evaluated in the “ON” state.
Comments: 
A distinct advantage of lixisenatide is that it is a repurposed drug, rather than a novel compound. As it is FDA-approved for Diabetes, it has a well-established safety and tolerability in humans. The aforementioned preclinical work in neurodegenerative and Parkinson’s models suggests that lixisenatide may be more effective than exenatide at engaging the GLP-1R target, reducing inflammation and promoting neuroprotection. An advantage of this study design for participants is that they do not have to be treatment naive; they can be on a stable Parkinson’s medication regimen during study participation. A disadvantage for participants is that the drug is administered as daily injections, as compared to weekly injections for other compounds (exenatide, NLY01 and semaglutide).

A Phase II, Randomized, Double-blinded, Placebo-controlled Trial of Liraglutide in Parkinson’s Disease

Status: 
Recruiting
Sponsor: 
Cedars-Sinai Medical Center
Enrollment: 
57
Study Design: 
This is a single center, double-blind, randomized placebo-controlled study. Subjects are randomized 2:1 to receive once daily self-administered injections of liraglutide (1.2 or 1.8 mg, as tolerated after a 2-week titration) or placebo at the same dose range. Participants will be followed for up to 56 weeks and will complete 9 in-person visits and 2 telephone visits. Eligible participants are those aged 25 to 85 with a diagnosis of idiopathic PD for at least 2 years. Notable exclusionary criteria include individuals with dementia (Mattis Dementia Rating Scale, MADRS-2, score <120), severe depression (BDI score > 29), Diabetes diagnosis, prior intracerebral surgical intervention, or current treatment with an anti-cholinergic medication.
Rationale: 
Primary Outcome Measures are: 1) change in motor function, determined by the change in MDS-UPDRS Part III scores at baseline, 28 and 54 weeks, 2) change in non-motor function determined by the change in Non-Motor Symptoms Scale (NMSS) score at baseline, 28 and 54 weeks, and 3) change in cognitive function, determined by the change in the MADRS-2 score at baseline, 28 and 54 weeks. Secondary Outcome Measures include: 1) change in peripheral insulin resistance, measured by the change in Homeostasis Model Assessment (HoMA-IR) index at baseline, 28 and 54 week visit, 2) change in the total MDS-UPDRS scores at baseline, 28 and 54 week visit, 3) change in quality of life determined by change in PDQ-39 scores at baseline, 28 and 54 weeks, 4) adverse events frequency, which will be monitored with vital signs, ECGs, urine and blood tests, at screening and follow-up visits.
Comments: 
Liraglutide has the advantage of being a re-purposed drug with established regulatory approval for Diabetes and obesity, and thus has an established safety and tolerability profile. Also similar between these two compounds is the demonstration of their neuroprotective effects in mouse models of PD, which proved superior to exenatide’s effects in these preclinical studies. A disadvantage of the drug is its once-daily injection, which will likely be less favorable to potential participants compared to exenatide and other once-weekly injected GLP-1 agonists under study (NLY01 and semaglutide).

A Study to Evaluate the Safety and Efficacy of IPX203 in Parkinson’s Disease Patients With Motor Fluctuations

Status: 
Recruiting
Sponsor: 
Impax Laboratories LLC (now Amneal)
Enrollment: 
510
Study Design: 
This is a multi-center (89 locations), randomized, double-blind, double-dummy, active-controlled, parallel-group study. It will consist of a 3-week, open-label IR CD-LD dose adjustment period; a 4-week, open-label period for conversion to IPX203; followed by a 13-week double-blind treatment period with subjects randomized in a 1:1 ratio, stratified by center, to receive either IPX203 (with matching IR CD-LD placebo) or IR CD-LD (with matching IPX203 placebo).
Rationale: 
The primary outcome is the change in “good ON” time. Secondary outcome measures are the change in OFF time; patients rated as “much improved” or “very much improved” in Patient Global Impression of Change (PGI-C); change in UPDRS Part III; and change in UPDRS Parts II and III. All the outcome measures will be assessed at the end of the double-blind study period at 13 weeks.
Comments: 
While symptomatic therapies for PD are easier to develop than drugs to modify the course of the disease, easier does not mean easy. This reality is underlined by the recent failure of the previously featured Phase 3 study of Intec Pharma’s Accordion Pill to reach its primary outcome objectives [3]. The Accordion Pill LD/CD containing both immediate and controlled release forms, presented with a unique gastric retentive drug delivery system which allowed for slow release of LD/CD in the stomach. According to the company website, on preliminary review, the study failed to demonstrate a statistically significant difference in OFF times as compared to the IR CD/LD arm. Further analysis and publication of data are pending [4]. The Phase 3 trial of IPX203 is thus a large and comprehensive program with a randomized, double-blind, double-dummy, active-controlled, parallel-group study design. The company’s experience with Rytary (codenamed IPX066 when in development) will be invaluable for the successful implementation of this pivotal Phase 3 study. While not groundbreaking, if successful, a new oral formulation of LD/CD with a longer duration of action will be a welcome addition to the armamentarium of available treatment options for PwPs.

Infusion of Apomorphine: Long-term Safety Study (INFUS-ON)

Status: 
Active, No Longer Recruiting
Sponsor: 
US WorldMeds
Enrollment: 
99
Study Design: 
This is a Phase 3, multicentre (18 locations), open-label, safety and tolerability study of continuous apomorphine infusion in subjects with advanced Parkinson’s Disease (PD) whose motor fluctuations remain unsatisfactory with levodopa (or levodopa/carbidopa) and at least one other class of drugs or mode of therapy for PD.
Rationale: 
The primary outcome is the percentage of OFF time during the waking day at week 12 compared to baseline. Secondary outcome measures are all based on efficacy: 1. Percent of daily “on” time without troublesome dyskinesias during waking day, baseline to Week 12; 2. Percent of daily “off” time during the waking day, baseline to weeks 2, 4, 8, 20, 28, 36, 44, and 52, and all treatment extension period visits; 3. Percent of daily “on” time without troublesome dyskinesias during the waking day, baseline to weeks 2, 4, 8, 20, 28, 36, 44, and 52, and all treatment extension period visits; 4. Percent of daily “on” time without dyskinesias, baseline visit to treatment weeks 2, 4, 8, 20, 28, 36, 44, and 52, and all treatment extension period visits; 5. UPDRS - Motor Score, baseline visit to week 12; 6. Clinical Global Impression of Severity (CGI-S) and Change (CGI-C) Scale, baseline visit to treatment weeks 2, 4, 8, 20, 28, 36, 44, and 52; and all treatment extension period visits; 7. Patient Global Impression of Severity (PGI-S) and Change (PGI-C) Scale, baseline visit to treatment weeks 2, 4, 8, 20, 28, 36, 44, and 52, and all treatment extension period visits; 8. Parkinson’s Disease Questionnaire, baseline visit to treatment weeks 2, 4, 8, 20, 28, 36, 44, and 52, and all treatment extension period visits; 9. UPDRS - Activities of Daily Living Score, baseline visit to treatment weeks 2, 4, 8, 20, 28, 36, 44, and 52, and all treatment extension period visits; 10. Proportion of responders, baseline visit to treatment weeks 2, 4, 8, 20, 28, 36, 44, and 52, and all treatment extension period visits; 11. Frequency and total dose of average daily intermittent injection of APOKYN for subjects on APOKYN treatment at study entry, baseline visit to treatment weeks 2, 4, 8, 20, 28, 36, 44, and 52, and all treatment extension period visits.
Comments: 
The INFUS-ON trial is aiming to recruit patients with advanced idiopathic PD, with unsatisfactory motor control despite optimised treatment and OFF periods ≥3 hours per day. Apomorphine is well accepted as efficacious in the treatment of OFF episodes in advanced PD and the rationale for continuous s.c. delivery makes sense. Hopefully, this study will enable drug approval in the US after many years of successful utilization in Europe.

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