A Trial to Test the Use of Dapansutrile, an Anti-inflammatory Medication, in People With Parkinson's Disease

NCT07157735 | Recruiting Phase 2 DMC

• 2 other identifiers: CCTU0443348480; 1010807
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

In Parkinson's disease (PD), there is inflammation in the brain, the gut and the blood, which is thought to contribute to the development and progression of the disease. The Nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is a complex of proteins which plays a critical role in mediating inflammation, and there is growing evidence from laboratory research that the inflammasome plays a role in Parkinson's disease. Dapansutrile is a new drug which has a highly specific effect on the NLRP3 inflammasome. In animal models, dapansutrile can protect against inflammation in the brain and prevent loss of dopamine cells. Initial 'in human' studies have indicated that this drug can effectively reduce inflammation without causing significant side effects. The goal of this clinical trial is to test whether dapansutrile might be a useful treatment for Parkinson's disease. The main questions it aims to answer are:

1. 1.is dapansutrile safe and well-tolerated in people with Parkinson's?
2. 2.does dapansutrile reduce inflammation in the brain, cerebrospinal fluid (CSF) and blood?

Conditions

Parkinson Disease

Keywords

Dapansutrile; Neurodegeneration; Neuroinflammation; Inflammation; NLRP3 inflammasome

Outcome Measures

Primary Outcomes (1)

• Number of adverse events (AEs) recorded during the 6-month double-blind period

  Adverse events are recorded from the point of participant informed consent and at every trial visit

  Assessed at screening, baseline, day 1, and weeks 2, 4, 6, 12, 18, 23 and 26.

Secondary Outcomes (15)

• Change in [¹⁸F]-DPA-714 PET non-displaceable binding potential in subcortical and cortical regions of interest

  Between baseline and week 23

• Change in concentration of C-reactive protein (CRP) in blood

  Over 6 months of treatment, measured at day 1, and weeks 6, 18 and 26.

• Change in concentration of interleukin (IL)-1β in blood

  Over 6 months of treatment, measured at day 1, and weeks 6, 18 and 26.

• Change in concentration of interferon (IFN)-γ in blood

  Over 6 months of treatment, measured at day 1, and weeks 6, 18 and 26.

• Change in concentration of IL-18 in blood

  Over 6 months of treatment, measured at day 1, and weeks 6, 18 and 26.

Other Outcomes (11)

• Number of AEs recorded

  During the 6-month open-label period

• Change in Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III

  Between baseline and 6 months, and over 12 months (if performed)

• Change in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) gait/axial score

  Between baseline and 6 months, and over 12 months (if performed).

Study Arms (2)

Research

ACTIVE COMPARATOR

Drug: dapansutrile

Control

PLACEBO COMPARATOR

Drug: placebo

Interventions

dapansutrile DRUG

Dapansutrile tablets administered for 26 weeks, starting at 1,000 mg daily (500 mg twice daily) for 4 weeks, escalated to 2,000 mg daily (1,000 mg twice daily) thereafter.

Research

placebo DRUG

Matched placebo tablets administered for 26 weeks, admistered as per the active treatment.

Control

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be included in the trial, the potential participant must:
• Have given written informed consent to participate.
• Be aged between 50 and 80 years (inclusive) at the time of the screening visit.
• Be a fluent English speaker.
• Have a diagnosis of clinically established early PD according to the Movement Disorder Society Criteria for Clinically Established Early Parkinson's Disease.
• Have a disease duration of less than 5 years at the time of screening visit.
• Have early-stage PD, defined as Hoehn and Yahr stage ≤2.
• Be PD drug naïve or be receiving a stable dose of dopaminergic therapy for at least 3 months prior to screening visit, or between screening and baseline.
• Have hsCRP \> 1 mg/L at screening visit.
• Have adequate organ function, as defined below (to be rechecked prior to baseline/investigational medicinal product \[IMP\] initiation if \>42 days from screening visit): Haemoglobin ≥ 110 g/L; Platelet count ≥ 130 × 109/L; Neutrophil count ≥ 1.5 × 109/L; Renal function: estimated glomerular filtration rate (eGFR) \>45 mL/min/1.73m2; Hepatic function: alanine aminotransferase (ALT) and bilirubin \< 1.5 times the institutional upper limit of normal; Thyroid stimulating hormone (TSH) within normal range; Corrected calcium ≤ institutional upper limit of normal; Alkaline phosphatase (ALP) \< 1.5 times the institutional upper limit of normal

You may not qualify if:

• Low affinity binder for TSPO ligands based on genotyping for single nucleotide polymorphism (SNP) rs6971.
• Any use of immunomodulatory drugs or biologic agents (such as azathioprine, mycophenolate, methotrexate, ciclosporin, cyclophosphamide etc.) within 12 months prior to screening visit, or between screening and baseline.
• Any previous use of rituximab or alemtuzumab at any time.
• Treatment with oral corticosteroids for greater than 2 weeks within 12 months prior to screening visit, or any oral or injected steroid use within 3 months prior to screening visit, or between screening and baseline.
• Regular use of non-steroidal anti-inflammatory drugs (NSAIDs) - including aspirin \> 75 mg, naproxen, ibuprofen and meloxicam - on more than 2 days per week.
• Known inflammatory or autoimmune disease.
• Chronic or latent infection.
• Severe infection requiring the use of parenteral antimicrobial agents within 2 months prior to screening visit, or between screening and baseline.
• Skin, solid organ or haematological malignancy within the 5 years prior to screening visit, or between screening and baseline.
• The inability to take or swallow oral medication.
• Parkinson's Disease Dementia according to Movement Disorder Society (MDS) PD Dementia criteria.
• A known genetic mutation associated with PD.
• A positive test for human immunodeficiency virus (HIV), hepatitis B (HBV)/C (HCV) or syphilis.
• Chronic liver disease.
• Any concurrent medical or psychiatric condition or disease that is likely to interfere with the trial procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this trial.

Sponsors & Collaborators

• University of Cambridge: collaborator
• Olatec Therapeutics LLC: collaborator
• Cure Parkinson's: collaborator
• Van Andel Research Institute: collaborator
• Cambridge University Hospitals NHS Foundation Trust: lead

Study Sites (1)

John Van Geest Centre for Brain Repair

Cambridge, CB2 0PY, United Kingdom

RECRUITING

MeSH Terms

Conditions

Parkinson Disease; Nerve Degeneration; Neuroinflammatory Diseases; Inflammation

Interventions

dapansutrile

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Caroline Williams-Gray, BMBCh MA(Cantab) FRCP PhD

  University of Cambridge

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Trial Coordinator

CONTACT

44 1223 331160; mcd68@cam.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participant, care provider, investigator and outcomes assessor will remain blinded until the end of the open label phase.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Optional open-label phase after 6 months

Study Record Dates

• First Submitted: May 15, 2025
• First Posted: September 5, 2025
• Study Start: February 2, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

GB (1)