Clinical Study of HER-096 in Healthy Volunteer Subjects and Patients with Parkinson's Disease

Inclusion Criteria:

Part 1:

1. Sufficient command of the Finnish language to be able to understand the subjectinformation leaflet and to communicate well with the study personnel.

2. Age 50-75 years at the time of consent.

3. Male or postmenopausal female.

4. BMI 18-35 kg/m2

5. Good general health, based on medical history, physical examination and laboratoryassessments.

6. Provision of written informed consent prior to any other trial related procedure isperformed.

7. Judged by the investigator to be alert and oriented to person, place, time andsituation when giving the informed consent.

Part 2:

1. Provision of written informed consent prior to any other trial related procedure isperformed.

2. Clinically established diagnosis of PD (MDS 2015 criteria), early idiopathic,Modified Hoehn and Yahr scale up to 2.5, with bradykinesia plus one of the othercardinal signs of PD (resting tremor, rigidity) being present, without any otherknown or suspected cause of PD.

3. Brain DAT-SPECT or DAT-PET imaging results consistent with PD.

4. Age 45-80 years at the time of consent; males and postmenopausal females.

5. Stable clinical disease state with either:

6. Patient does not require dopaminergic PD medication and is not expected torequire dopaminergic treatment within the study duration, or

7. Stable treatment including one or any combination of below treatments, asclinically established and well tolerated i. Levodopa substitution with oral levodopa + DOPA decarboxylase inhibitor (not morethan 1000 mg levodopa daily) ii. Orally administered dopamine agonists excludingergot-derived- agonist drugs iii. Transdermal rotigotine patches iv. Monoamineoxidase B (MAO-B) inhibitor c. All treatments of PD should be stable for at least 45days prior to baseline assessments and not expected to change within the studyduration.

8. Good general health (apart from PD), based on medical history, physical examinationand laboratory assessments.

9. BMI 18-35 kg/m2.

Exclusion Criteria:

Part 1:

1. Predicted poor compliance with study procedures, restrictions and requirements.

2. Veins unsuitable for repeated venepuncture or cannulation.

3. History or evidence of current clinically significant cardiovascular, pulmonary,renal, hepatic, gastrointestinal, haematological, metabolic-endocrine, neurological,urogenital or psychiatric disorder. Subjects with any type of generalized seizuresin adulthood must be excluded. Personal or first-degree family history of congenitallong QT syndrome or sudden death of a first-degree relative suspected to be due tolong QT syndrome will also exclude the subject.

4. MRI (3 T) of the brain with indication of clinically significant CNS disorder.

5. History of any type of cancer, except for the age group of above 65 years, where ahistory of successfully treated cancer, with at least 5 years since the end oftreatment, or local prostate cancer with no evidence of disease progression underadequate active surveillance, may be allowed at the investigator's discretion.

6. Susceptibility to severe allergic reactions, e.g. history of anaphylactic shock dueto any reason.

7. Any condition requiring regular concomitant medication (including non-prescriptionalover-the-counter (OTC) drugs), or likely to need any concomitant medication duringthe study. As exceptions, hormone replacement therapy in female subjects andsupplementation therapy with thyroxin, iron, calcium, folate and vitamin B12 atrecommended doses is allowed. Vitamin D supplementation at doses of 20 µg/day orless is also allowed. The use of other vitamins, nutritional supplements and herbalproducts, at recommended doses, may be allowed at the investigator's discretion.Occasional use of paracetamol for pain is allowed.

8. Use of any medication that might affect the study results or cause a health risk forthe subject within 2 weeks prior to IMP administration.

9. Any clinically significant abnormalities in screening laboratory test results, vitalsigns or physical examination findings that might influence the results of the studyor cause a health risk for the subject if he/she takes part in the study.

10. Estimated glomerular filtration rate (eGFR) below 60 ml/min/1,73 m2

11. Coagulopathy, thrombocytopenia, use of anticoagulants or other antithromboticagents.

12. Positive serology to human immunodeficiency virus antibodies (HIVAgAb), hepatitis Cvirus antibodies (HCVAb) or hepatitis B surface antigen (HBsAg).

13. Any clinically significant 12-lead ECG abnormality after 10 min rest in supineposition at the screening visit or baseline evaluation at the dosing visit. Forexample, any of the following findings in the resting ECG:

14. QTcF above 450 or below 300 msec;

15. Notable resting bradycardia (heart rate (HR) below 45 beats per minute (bpm))or tachycardia (HR above 100 bpm);

16. Screening or baseline ECG with QRS and/or T wave judged to be unfavourable fora consistently accurate QT measurement (e.g., neuromuscular artifact thatcannot be readily eliminated, arrhythmias, indistinct QRS onset, low amplitudeT wave, merged T- and U-waves, prominent U waves);

17. Evidence of atrial fibrillation, atrial flutter, complete bundle branch block,Wolf-Parkinson-White syndrome, or cardiac pacemaker.

18. HR below 45 bpm or above 85 bpm, systolic blood pressure (BP) below 90 mmHg or above 150 mmHg, or diastolic BP below 50 mmHg or above 95 mmHg after 10 min rest in supineposition at the screening visit.

19. History of alcohol or drug abuse within the last 5 years, or current regular use ofillicit drugs or excessive use of alcohol (regular alcohol drinking of more than 24units/week for males or 14 units/week for females).

20. Positive breath test for alcohol or positive urine screening test result for drugsof abuse.

21. Current use of nicotine-containing products of more than 5 cigarettes or equivalentper day, or inability to refrain from using nicotine-containing products during thestay at the study centre.

22. Inability to refrain from consuming caffeine-containing beverages during the stay atthe study centre.

23. Participation in any other clinical drug study within 3 months before the IMPadministration of this study.

24. Donation of blood within 3 months before the IMP administration.

25. Any medical or surgical procedure planned during the study period.

26. Male subjects who are sexually active with a female partner of childbearingpotential and do not agree to use two medically accepted methods of contraceptionduring the study and for three months after the dosing, and refrain from donatingsperm during this time.

27. Female subjects need to be postmenopausal for at least one (1) year beforeparticipation or be surgically sterilized.

28. Any indication of increased intracerebral pressure by neurological examination orother contraindication for lumbar puncture.

29. Any contraindication for MRI of the brain.

30. Large tattoo or another condition of the skin or subcutaneous tissue that wouldprevent reliable assessment of local injection site reactions.

31. Significant risk of suicidal behaviour, defined using the C-SSRS, as the subjectanswering "yes" at the screening visit to suicidal ideation questions 4 or 5 oranswering "yes" to suicidal behaviour within the past 6 months.

Part 2:

1. Predicted poor compliance with study procedures, restrictions and requirements.

2. Veins unsuitable for repeated venepuncture or cannulation.

3. History or evidence of current clinically significant, potentially unstablecardiovascular, pulmonary, renal, hepatic, gastrointestinal, haematological,metabolic-endocrine or urogenital disorder. Persons with stable chronic diseases maybe included at the investigator's discretion. Subjects with any type of generalizedseizures in adulthood must be excluded. Personal or first-degree family history ofcongenital long QT syndrome or sudden death of a first-degree relative suspected tobe due to long QT syndrome will also exclude the subject.

4. History of major psychiatric disorder, including schizophrenia and bipolar illness.A subject with a history of major depressive disorder (MDD) that is considered to bein remission or controlled with treatment can be included in the trial perinvestigator's judgement.

5. History of any type of cancer, except for the age group of above 65 years, where ahistory of successfully treated cancer, with at least 5 years since the end oftreatment, or local prostate cancer or fully excised non-melanoma skin cancers withno evidence of disease progression under adequate active surveillance for at least 6months, or cervical intraepithelial neoplasia stage I uterine cancer may be allowedat the investigator's discretion.

6. Other neurological disorder than PD, including Alzheimer's disease, ALS, multiplesclerosis, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP),multiple system atrophy (MSA), Parkinson's disease dementia (PDD) and other movementdisorders with overlapping symptomatology to PD.

7. Wearing-off or dyskinesia in relation to dopaminergic treatment.

8. Treatment with levodopa infusions, apomorphine infusions or other non-oral PDmedications (except for transdermal rotigotine patches).

9. Ongoing or previous treatment of PD with deep brain stimulation (DBS) orhigh-intensity ultrasound (HIFU).

10. Coagulopathy, thrombocytopenia, use of anticoagulants or other antithromboticagents.

11. Susceptibility to severe allergic reactions, e.g. history of anaphylactic shock dueto any reason.

12. Ongoing treatment with antipsychotic medications, or use of other medications thatin the opinion of the investigator might cause a risk for the study participant orjeopardise the study assessments. Disallowed medications include e.g. systemicallyused glucocorticoids and other modulators of immune functions.

13. Any clinically significant abnormalities in screening laboratory test results, vitalsigns or physical examination findings that might influence the results of the studyor cause a health risk for the subject if he/she takes part in the study.

14. Estimated glomerular filtration rate (eGFR) below 60 ml/min/1,73 m2

15. Positive serology to human immunodeficiency virus antibodies (HIVAgAb), hepatitis Cvirus antibodies (HCVAb) or hepatitis B surface antigen (HBsAg).

16. History of alcohol or drug abuse within the last 5 years, or current regular use ofillicit drugs or excessive use of alcohol (regular alcohol drinking of more than 24units/week for males or 14 units/week for females).

17. Positive breath test for alcohol or positive urine screening test result for drugsof abuse.

18. Current use of nicotine-containing products of more than 10 cigarettes or equivalentper day, or inability to refrain from using nicotine-containing products during thestay at the study centre.

19. Participation in any other clinical drug study within 3 months before the first IMPadministration of this study.

20. Donation of blood within 3 months before the first IMP administration.

21. Any medical or surgical procedure planned during the study period.

22. Male subjects who are sexually active with a female partner of childbearingpotential and do not agree to use two medically accepted methods of contraceptionduring the study and for three months after the last dosing, and refrain fromdonating sperm during this time.

23. Female subjects need to be postmenopausal for at least one (1) year beforeparticipation or be surgically sterilized.

24. Any contraindication MRI of the brain.

25. MRI (3 T) of the brain with indication of clinically significant CNS disorder apartfrom PD.

26. For subjects scheduled to undergo DAT-SPECT: any contraindication for DAT-SPECT ofthe brain, including previous hypersensitivity reactions to iodine administration.

27. Any indication of increased intracerebral pressure by neurological examination atinclusion, or another contraindication for LP.

28. Any condition expected to require changes in medical treatment during the trialperiod, or use of disallowed concomitant medications, or concomitant medication thathas not been stable for at least 45 days prior to baseline assessments. The usevitamins, nutritional supplements and herbal products, at recommended doses, may beallowed at the investigator's discretion. Occasional use of paracetamol for pain isallowed. Hormone replacement therapy in female subjects and supplementation therapywith thyroxin, iron, calcium, folate and vitamin B12 at recommended doses isallowed. Vitamin D supplementation at doses of 20 µg/day or less is also allowed.

29. Large tattoo or another condition of the skin or subcutaneous tissue that wouldprevent reliable assessment of local injection site reactions.

30. Significant risk of suicidal behaviour, defined using the C-SSRS, as the subjectanswering "yes" at the screening visit to suicidal ideation questions 4 or 5 oranswering "yes" to suicidal behaviour within the past 6 months.

31. Previous treatment with any investigational and/or marketed passive immunotherapyagainst PD within 6 months before screening or 5 half-lives, whichever is longer,unless there is firm evidence that the subject received placebo only (in the case ofany investigational product administered within the frame of a clinical trialparticipation).

32. Participation in previous clinical trials for PD and/or for neurological disordersusing any small molecule drug with a washout <30 days or <5 half-lives of the drug,whichever is longer before screening, unless there is firm evidence that the subjectreceived placebo only.

33. Concomitant participation in any other clinical trial using experimental or approvedmedications or therapies (e.g., device, stem cells). This does not includenoninterventional devices for disease tracking or imaging studies.