Dapansutrile to reduce inflammation in people with early Parkinson's disease.

Anti-inflammatory Intervention With Dapansutrile (OLT1177®) for Parkinson's Disease Modification (DAPA-PD): A Randomised Double-Blind, Placebo-Controlled Phase II Trial

This will test whether the anti-inflammatory drug dapansutrile is safe and can reduce inflammation in people aged 50–80 with early Parkinson's disease who have raised CRP.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 50 Years to 80 Years
• Sex: All
• Sponsor: Cambridge University Hospitals NHS Foundation Trust (Academic / other)
• Drugs / interventions: rituximab, alemtuzumab, methotrexate, cyclophosphamide
• Locations: 1 site (Cambridge)
• Trial ID: NCT07157735 on ClinicalTrials.gov

What this trial studies

DAPA-PD is a randomized, double-blind, placebo-controlled Phase II trial at a single Cambridge site enrolling 36 people with early Parkinson's disease and evidence of peripheral inflammation (hsCRP >1 mg/L). Participants are randomized 2:1 to dapansutrile 1000 mg twice daily or placebo for 6 months, followed by an optional 6-month open-label phase where all receive the active drug. The primary outcome is safety and tolerability over the 6-month placebo-controlled period, with secondary measures including blood and CSF inflammatory biomarkers, TSPO PET brain imaging, pharmacokinetics, and clinical motor and cognitive measures. Safety monitoring includes venous blood tests, ECGs, and regular clinical assessments throughout both phases.

Who should consider this trial

Good fit: Ideal participants are people aged 50–80 with clinically established early Parkinson's disease (disease duration ≤5 years, Hoehn and Yahr stage ≤2) who have hsCRP >1 mg/L and are either drug-naïve or on a stable dopaminergic regimen.

Not a fit: People with advanced Parkinson's disease, low systemic inflammation (hsCRP ≤1 mg/L), significant organ dysfunction, or who cannot travel to the Cambridge site are unlikely to benefit from or be eligible for this trial.

Why it matters

Potential benefit: If successful, dapansutrile could reduce harmful inflammation and potentially slow motor or cognitive progression in early Parkinson's disease while being well tolerated.

How similar studies have performed: Preclinical studies and early human trials of dapansutrile and other NLRP3 inhibitors have shown reduced inflammation and neuroprotection in models, but definitive clinical benefit in Parkinson's disease has not yet been demonstrated.

Eligibility criteria

Inclusion Criteria:

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

Exclusion Criteria:

The presence of any of the following will preclude inclusion:

* 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.
* Women of childbearing potential - female participants must be surgically sterile or be post-menopausal. (A post-menopausal state is defined as no menses for 12 months without an alternative medical cause).
* Male participants must be surgically sterile or must agree to use effective contraception during the period of therapy and for 6 months after the last dose of the trial treatment.
* Known hypersensitivity to dapansutrile or its excipients.
* Received an investigational drug or used an invasive investigational medical device within 12 weeks before the screening assessment, or is currently enrolled in another interventional investigational trial. Participants currently enrolled in other observational studies may be recruited.
* Contraindications to PET-magnetic resonance imaging (MRI) scanning including metal implants, claustrophobia or inability to lie flat for 90 minutes.
* Concomitant treatment with any medications that could interfere with \[18F\] DPA-714 binding (e.g., benzodiazepines).
* Current use of any drugs of abuse or average alcohol intake of \>21units per week over the last 3 months.
* Any other significant disease, disability or investigation result which, in the opinion of the Chief Investigator (CI), may either put the participant at risk, or may influence the result of the trial, or the participant's ability to participate in the trial.

Where this trial is running

Cambridge

• John Van Geest Centre for Brain Repair — Cambridge, United Kingdom (Recruiting)

Study contacts

• Principal investigator: Caroline Williams-Gray, BMBCh MA(Cantab) FRCP PhD — University of Cambridge
• Study coordinator: Trial Coordinator

Conditions Parkinson Disease; Dapansutrile; Neurodegeneration; Neuroinflammation; Inflammation; NLRP3 inflammasome