A Multi-arm Clinical Trial Accelerator and Derisking Platform for Parkinson’s Disease (PD)
PD is the fastest growing neurological condition worldwide, with..
WHY SO MANY TRIALS FAIL?
Despite numerous completed clinical trials, we still lack disease modifying therapies that can slow or halt the progression of Parkinson’s disease. A major reason is that many candidate drugs advance into late-stage trials without solid evidence that they engage their biological targets. As a result, large and costly trials often fail, delaying progress toward effective treatments.
SLEIPNIR:
AN INNOVATIVE APPROACH
SLEIPNIR directly addresses this gap. The platform is designed to determine early whether a potential disease-modifying therapy penetrates the central nervous system (CNS) and acts on its intended target. By filtering out ineffective compounds early, SLEIPNIR enables a smarter, faster, and more efficient pathway to treatment development for Parkinson’s disease, focusing resources only on the treatments with the highest likelihood of success.
DESIGN
SLEIPNIR is a Phase 2a, randomized, double-blind, biomarker-driven, multi-arm platform trial designed to test several potential disease-modifying treatments for Parkinson’s disease in parallel. Each treatment is evaluated in its own cohort, but all cohorts share a common trial infrastructure and, when scientifically valid, a pooled contemporary placebo group.
The platform uses a two-step randomization process:
1. Randomization across active cohorts that are open at the same time.
2. Randomization within each cohort to either active treatment or matching placebo.
Because only contemporary placebo participants are used for comparison, the allocation ratio (active:placebo) may differ between cohorts to ensure sufficient control numbers and scientific validity.
Each participant undergoes:
· Up to 8 weeks of screening, including optimization of standard of care medication.
· 12 weeks of treatment with either an investigational compound or placebo.
· 2 weeks of safety follow-up after the last dose.
All participants provide CSF and blood samples and undergo brain imaging to measure:
· CNS penetration of the compound (via CSF-to-plasma ratios)
· Target engagement in the CNS (compound-specific biomarkers)
SLEIPNIR is non-adaptive: all study arms run to completion unless stopped for safety reasons. New compounds can enter the platform asynchronously, allowing rapid evaluation of emerging therapeutic candidates.
Only treatments that demonstrate acceptable safety, robust CNS penetration, and clear evidence of target engagement will be recommended for advancement into later-phase efficacy trials
OBJECTIVES
Safety: To evaluate the safety and tolerability of each investigational compound
CNS penetration: To determine whether each compound enters the human brain, measured by CSF-to-plasma concentration ratios of the parent drug and/or relevant metabolites at steady state.
Target engagement: To assess whether each compound acts on its intended biological target within the CNS. This is evaluated using compound-specific biomarkers in CSF (and supportive blood/imaging markers), reflecting the expected molecular or biochemical effect of the treatment in the brain.
INCLUSION CRITERIA
Participants are eligible to be included in the study only if all of the following criteria apply:
Participant must be 40 to 85 years of age inclusive, at the time of signing the informed consent.
Participants who are diagnosed with clinically established PD as defined by the MDS Clinical Diagnostic Criteria, meeting all of the following: a) Diagnosis of PD within 10 years of enrollment, b) Hoehn and Yahr score of ≤3 at enrolment, and c) On stable anti-parkinsonian treatment (not starting new anti-parkinsonian medications, or changes in current doses for a period of at least 2 weeks prior to baseline.
Body weight within 45-120Kg (inclusive).
Male or female assigned at birth, inclusive of all gender identities. Contraceptive requirements apply during the entire treatment period, and following a washout period of 8 weeks after last intake of the last study intervention, or within 5 half-lives of the experimental treatment, whichever is longer.
Male participants must: a) Refrain from donating fresh unwashed semen. b) Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR must agree to use a male condom when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: a) Is a woman of non-childbearing potential. b) Is a Woman of Childbearing Potential (WOCBP) and using a contraceptive method that is highly effective (with a failure rate of < 1% per year). c) A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within 24 hours before the first dose of study intervention.
Signed informed consent.
Presence of dopaminergic nigrostriatal denervation documented by dopamine transporter (DAT) single photon emission tomography (SPECT) or positron emission tomography (PET), or [18F]DOPA-PET.
Lack of evidence of other neurodegenerative disorders or any severe somatic or mental illness that may interfere with the study.
Are able to undergo MRI, blood sampling, and lumbar puncture (LP).
EXCLUSION CRITERIA
Participants are excluded from the study if any of the following criteria apply:
Known or suspected cause of parkinsonism other than neurodegenerative idiopathic PD, including but not limited to atypical parkinsonian syndromes (e.g., progressive supranuclear palsy (PSP), or multiple system atrophy (MSA), corticobasal syndrome (CBS), dementia with Lewy bodies (DLB), drug-induced parkinsonism (e.g., neuroleptics, metoclopramide, etc.), encephalitis, known monogenic disorders, etc.
Known or suspected neurodegenerative disorders other than neurodegenerative idiopathic PD.
Differential diagnoses to PD, including atypical parkinsonism or other neurodegenerative disorders.
MoCA score < 23, dementia, or other significant cognitive impairment that, in the opinion of the Investigator, would interfere with study evaluation.
History of any brain surgery for PD (e.g., pallidotomy, deep brain stimulation, or fetal tissue transplant) or history of focused ultrasound treatment at any time; or history of neuromodulation procedures, including, but not limited to, transcranial magnetic
stimulation (TMS), transcranial direct or alternating current stimulation (tDCS/tACS) that have been performed within 90 days of screening.
History of unstable angina, myocardial infarction, chronic heart failure (New York Heart Association Class 3 or 4), or clinically significant conduction abnormalities (e.g., unstable atrial fibrillation) within 1 year before Screening.
Poorly controlled diabetes mellitus, as defined by having dosage adjustment of diabetic medication within 3 months before dosing (Day 1) or glycosylated hemoglobin ≥ 8% at Screening.
History of active malignancy. At Investigator’s discretion, participants with a history of malignancy that is considered cured can participate.
History of solid organ transplantation.
History of alcohol/substance abuse within 1 year from baseline.
History of any psychiatric disorder that would interfere with the participant’s ability to comply with the study, as determined by the Investigator.
History of any somatic illness that would interfere with the participant’s ability to comply with the study, as determined by the Investigator.
Participant is currently prescribed a drug/nutraceutical that interacts with the study intervention (contact us for details).
Participant is enrolled in a current clinical trial or has been enrolled in a clinical trial of an experimental therapy within the 30 days prior to Screening and/or within 5 half-lives of the IMP, whichever is longer.
Prolonged QT-interval with QTcF > 480 ms at screening or baseline (the mean of the triplicate QTcF values will be used). QT intervals will be corrected for heart rate using Fridericia’s formula (QTcF = QT / RR^(1/3)), in accordance with ICH E14 recommendations.
Any ECG abnormality or rhythm disturbance that, in the opinion of the investigator, poses a significant risk of ventricular arrhythmia.
History or positive test result at Screening for human immunodeficiency virus (HIV) or hepatitis C virus antibody.
Current hepatitis B virus (HBV) infection (defined as positive for hepatitis B surface antigen [HbsAg]). Participants with immunity to hepatitis B from previous natural infection (defined as negative HbsAg, positive anti-HBc, and positive hepatitis B surface antibody [anti-HBs]) or vaccination (defined as negative HbsAg, negative anti-HBc, and positive anti-HBs) are eligible to participate in the study.
Currently active infection or serious infection (e.g., pneumonia, septicemia) within 8 weeks before Day 1, as determined by the Investigator.
Liver function test results (ALAT, ASAT, bilirubin) ≥ 1.5 times the upper limit of normal at the Screening Visit (participants with previously diagnosed Gilbert’s syndrome and elevated levels of bilirubin consistent with such diagnosis may be allowed in the study).
Urinary albumin/creatinine ratio (ACR) ≥ 20 mg/mmol at time of enrollment.
Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 at screening.
Screening value for hemoglobin < 12 g/dL for men or < 11 g/dL for women.
Platelet count < 100 x 109/L.
Participants with abnormal test results may be rescreened one time at the discretion of the Investigator. Participants with clinically nonsignificant out-of-range laboratory results may be enrolled at the discretion of the Investigator after consultation with the Medical Monitor and/or Study Director.
Use of Mucuna pruriens within 90 days before baseline and for the duration of the study.
Any contraindications to having a brain MRI (e.g., pacemaker; MRI-incompatible implants; claustrophobia that cannot be managed without general anesthesia, etc.).
Any contraindications to having a lumbar puncture: Contraindications as defined by institutional guidelines:
a. Increased intracranial pressure and/or space-occupying lesion
b. Spinal epidural abscess
c. Infection in or near the puncture site
d. Known spinal stenosis with myelopathy or spinal cord compression above level of
puncture
e. Known spinal or cranial developmental abnormalities
f. Increased risk of bleeding (platelet count < 40 x 109/L, INR ³ 1.4, use of anticoagulants other than acetylsalicylic acid (ASA 75 mg once daily), use of NSAIDs that cannot be discontinued within the recommended timeframe according to institutional guidelines for each specific drug, known increased bleeding risk from other causes, deemed clinically significant by the investigator)
Known allergies to active IMP.