Single Ascending Doses of HER-096 in Healthy Subjects

Phase I, Randomised, Double-Blind, Placebo-Controlled, Safety, Tolerability and Pharmacokinetic Study of Subcutaneous Single Ascending Doses of HER-096 to Healthy Volunteer Subjects

This study evaluates the safety and tolerability of HER-096 in healthy volunteer subjects by comparing the effects of active study treatment HER-096 to placebo (0.9% physiological saline). In addition, the pharmacokinetic profile of HER-096 in humans will be investigated. The investigational medicinal products will be administered as a single dose by subcutaneous injection.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Placebo; Drug: HER-096

Detailed Description

This is a Phase I, double-blind, placebo-controlled, clinical study, in which safety, tolerability and pharmacokinetic profile of HER-096 will be investigated after a subcutaneously (s.c.) administered single ascending doses of HER-096 to healthy volunteer subjects (HVS).

Altogether 60-64 HVS will be enrolled into the study and the study will be conducted in two parts, part 1 being randomised and part 2 being open-label. In part 1, up to 48 young male HVS will be randomised 6:2 either to receive HER-096 or placebo (0.9% physiological saline) solution. In part 1, up to 6 dosing cohorts have been planned with single ascending doses of HER-096. In part 2, 12-16 older and elderly HVS, both males and females, will be administered with single dose of HER-096 to evaluate the blood-brain-barrier penetration of HER-096. The investigational medicinal products (HER-096 or placebo solution) will be administered as a s.c. injection.

The total duration of the study will be up to 36 days for each subject, consisting of screening and treatment period.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Finland
  • Turku, Finland
    • Clinical Research Services Turku - CRST Oy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Voluntary and written informed consent and alert and oriented to person, place, time and situation at the time of the informed consent.
2. Sufficient command of the Finnish language.
3. Age 20-45 years for Part 1 and 50-75 years for Part 2.
4. Male sex for Part 1, and male or female for Part 2.
5. Body mass index (BMI) 18-30 kg/m2.
6. Good general health.

Exclusion Criteria:

1. Predicted poor compliance with study procedures, restrictions and requirements.
2. Veins unsuitable for repeated venipuncture 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 seizures in adulthood must be excluded. Personal or first-degree family history of congenital long QT syndrome or sudden death of a first-degree relative suspected to be due to long QT syndrome will also exclude the subject.
4. History of any type of cancer, except for the age group of >50 years, where a history of successfully treated cancer may be allowed.
5. Susceptibility to severe allergic reactions, e.g. history of anaphylactic shock.
6. Any condition requiring regular concomitant medication (including non-prescriptional over-the-counter drugs), or likely to need any concomitant medication during the study.
7. Use of any medication that might affect the study results or cause a health risk for the subject within 2 weeks prior to IMP administration.
8. Any clinically significant abnormalities in screening laboratory test results, vital signs or physical examination findings that might influence the results of the study or cause a health risk for the subject if he/she takes part in the study.
9. Coagulopathy, thrombocytopenia, use of anticoagulants or other antithrombotic agents.
10. Positive serology to human immunodeficiency virus antibodies (HIVAgAb), hepatitis C virus antibodies (HCVAb) or hepatitis B surface antigen (HBsAg).
11. Any clinically significant 12-lead ECG abnormality.
12. HR < 45 bpm or > 85 bpm, systolic blood pressure (BP) < 90 mmHg or > 150 mmHg, or diastolic BP < 50 mmHg or > 90 mmHg.
13. History of alcohol or drug abuse within the last 5 years, or current regular use of illicit drugs or excessive use of alcohol.
14. Positive breath test for alcohol or positive urine screening test result for drugs of abuse.
15. Current use of nicotine-containing products of more than 5 cigarettes or equivalent per day, or inability to refrain from using nicotine-containing products.
16. Inability to refrain from consuming caffeine-containing beverages.
17. Participation in any other clinical drug study within 3 months before the IMP administration of this study.
18. Donation of blood within 3 months before the IMP administration.
19. Any medical or surgical procedure planned during the study period.
20. Male subjects who are sexually active with a female partner of childbearing potential and do not agree to use two medically accepted methods of contraception during the study and for three months after the dosing, and refrain from donating sperm during this time.
21. Female subjects for Part 2 need to be postmenopausal for at least one (1) year before participation or be surgically sterilized.
22. For subjects in Part 2, any indication of increased intracerebral pressure by neurological examination at inclusion, or another contraindication for LP.
23. Large tattoo or another condition of the skin or subcutaneous tissue that would prevent reliable assessment of local IREs.
24. Significant risk of suicidal behaviour, defined using the C-SSRS.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo (Part 1); Corresponding volumes of placebo solution according to the dosing cohort administered as a s.c. injection.	Drug: Placebo; Administered as a single dose via s.c. injection; Other Names: 0.9% physiological saline; Sodium chloride 9 mg/ml
Active Comparator: HER-096 (Part 1); Single ascending doses of HER-096 up to six dosing cohorts administered as a s.c. injection.	Drug: HER-096; Administered as a single dose via s.c. injection
Active Comparator: HER-096 (Part 2); A single dose of HER-096 will be administered as a s.c. injection.	Drug: HER-096; Administered as a single dose via s.c. injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs)	Incidence, type and severity of treatment-emergent AEs	8 +/- 1 days
Physical examination	Incidence of clinically significant physical examination findings	8 +/- 1 days
Vital signs	Incidence of clinically significant findings in systolic and diastolic blood pressure, heart rate and body temperature	8 +/- 1 days
12-lead electrocardiogram (ECG)	Incidence of clinically significant findings in heart rate, PR interval, RR, QRS interval and QTcF	24 hours
Pulse oximetry	Incidence of clinically significant changes in blood oxygen saturation	8 hours
Laboratory safety assessments - Haematology	Incidence of clinically significant laboratory variables in haemoglobin, erythrocytes, leucocytes, thrombocytes, mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC) and differential leucocyte count	8 +/- 1 days
Laboratory safety assessments - Clinical chemistry	Incidence of clinically significant laboratory variables in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), bilirubin total, bilirubin conjugated, albumin, creatinine, glucose, sodium, potassium, calcium, C-reactive protein (CRP), creatine kinase (CK), thyroid-stimulating hormone (TSH) and prolactin	8 +/- 1 days
Laboratory safety assessments - Coagulation	Incidence of clinically significant laboratory variables in plasma activated partial thromboplastin time (P-APTT) and international normalized ratio (INR)	8 +/- 1 days
Laboratory safety assessments - Urinalysis	Incidence of clinically significant laboratory variables in pH, erythrocytes, leukocytes, nitrite, protein, glucose and ketones	8 +/- 1 days
Laboratory safety assessments - CSF (Part 2 only)	Incidence of clinically significant laboratory variables in cell count and protein concentration	12 hours
Columbia-Suicide Severity Rating Scale (C-SSRS)	Incidence of subjects with increased suicidal tendencies measured by C-SSRS questionnaire consisting of maximum of 4 sections. Suicidal ideation: 5 yes/no questions with "yes" indicating suicidal ideation and "no" indicating no suicidal ideation. Intensity of ideation: 5 questions to be rated with respect to the most severe type if ideation (5 being the most severe intensity and 1 being the least intensity). Suicidal behavior: 5 yes/no questions with "yes" indicating suicidal behavior and "no" indicating no suicidal behavior. Actual attempts only: 2 questions to be rated with respect to the most severe outcome of the suicide attempt (highest score indicating the most severe outcome and 0 indicating no harm).	8 +/- 1 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HER-096 concentration levels	Changes in HER-096 concentration levels in plasma and urine	24 hours
HER-096 concentration in CSF (Part 2 only)	Changes in HER-096 concentration levels in CSF	12 hours

Collaborators and Investigators

• Sponsor: Herantis Pharma Plc.
• Collaborators: Clinical Research Services Turku - CRST Oy
• Investigators: Principal Investigator: Aleksi Tornio, MD, Clinical Research Services Turku - CRST Oy

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2023
• Primary Completion (Actual): September 29, 2023
• Study Completion (Actual): September 29, 2023

Study Registration Dates

• First Submitted: May 8, 2023
• First Submitted That Met QC Criteria: June 13, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 25, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Parkinson Disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: 13-XC-CL; 2022-003283-24 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No