A Two-Part Single and Multiple Ascending Dose Trial of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LBT-3627 in Healthy Participants and in Participants With Parkinson's Disease.

Phase I a/b SAD/MAD study to evaluate safety and tolerability of LBT-3627 in both healthy volunteers and Parkinson's patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Placebo; Drug: LBT-3627

Detailed Description

Evaluate the safety and tolerability of LBT-3627 in both a single and multiple ascending dose study.

Phase Ia will explore safety and tolerability first in healthy volunteers then followed by Parkinson's patients after a single dose. Dose levels will escalate per cohort.

Phase Ib will explore safety and tolerability in Parkinson's patients after multiple doses. Dose levels will escalate per cohort.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Tim Porter, MBBS, FANZCA, MBioethics; Phone Number: +61 450992172; Email: Tim.Porter@avancecro.com

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia
      • Alfred Hospital
      • Contact: Jack Germaine; Phone Number: +61 487 531 448; Email: NeurologyClinicaltrials@alfred.org.au
    • Melbourne, Victoria, Australia
      • Nucleus Networks
      • Contact: Ofer Gonen; Phone Number: 1800 243 733; Email: melbourne@nucleusnetwork.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria (Everyone)

Participants will be included in the study only if they satisfy all the following criteria:

1. Must have given written informed consent, before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
2. Healthy male or female, aged between 30 and 89 years, inclusive at screening.
3. Body mass index (BMI) of 18 to 32 kg/m2, inclusive.

4. Participant is medically healthy (in the opinion of the Investigator [or delegate]), as determined by pre-study medical history and without clinically significant abnormalities including:

   1. Physical examination without any additional clinically relevant findings

   2. Systolic blood pressure in the range of 90 to 140 mmHg and diastolic blood pressure in the range of 40 to 90 mmHg after 5 minutes in supine/semi-supine, and subsequently after 3 minutes of standing position.

      Note: Participants with orthostatic hypotension are not permitted. Orthostatic hypotension is defined as ≥ 20 mm Hg reduction in systolic blood pressure and/or ≥ 10 mm Hg reduction in diastolic blood pressure between supine/semi-supine versus subsequent standing measurements.

   3. Heart rate in the range of 50 to 100 beats/minute after 5 minutes rest in supine/semi-supine position, and subsequently after 3 minutes of standing position.

      Note: Participants with orthostatic hypotension are not permitted. Orthostatic hypotension is defined as ≥ 30 beats/minute increase in heart rate between supine/semi-supine versus subsequent standing measurements.

   4. Body temperature (tympanic), between 35.5°C and 37.5°C.
   5. Electrocardiogram (ECG) without clinically significant abnormal including QT interval corrected for Fredericia (QTcF) < 450 msec for male participants and < 470 msec for female participants.
   6. No clinically significant findings in serum chemistry, haematology, coagulation or urinalysis (in the opinion of the Investigator).

5. Female participants must be of non-child-bearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before the screening visit) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone [FSH] level consistent with postmenopausal status, per local laboratory guidelines), or, if of child-bearing potential:

   1. Must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test on Day -1, prior to dose administration.
   2. Must agree not to donate ova or attempt to become pregnant from the time of signing consent until at least 30 days after the last dose of study drug.
   3. If not exclusively in a same-sex relationship, must agree to remain abstinent throughout the study, or must agree to use adequate contraception (which is defined as use of a condom by the male partner combined with use of a highly effective method of contraception from one month prior to screening until at least 30 days after the last dose of study drug.

6. Male participants must:

   1. Agree not to donate sperm from the time of signing consent until at least 30 days after the last dose of study drug.
   2. If engaging in sexual intercourse with a female partner who could become pregnant, agree to use adequate contraception (defined as use of a condom plus a highly effective method of contraception from the time of signing consent until at least 30 days after the last dose of study drug.
   3. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, agree to use a condom from the time of signing consent until at least 30 days after the last dose of study drug.
7. Willing and able to comply with all scheduled visits, treatment plans, laboratory tests and other study procedures.

Exclusion Criteria (Everyone)

Participants will be excluded from the study if there is evidence of any of the following:

1. Use of immunomodulators (including steroids and topical/oral/inhaled OTC glucocorticoids) within the past 90 days prior to the start of the first dose of study drug.
2. Use of coenzyme Q10 within 5 days prior to the start of the first dose of study drug.
3. Received a vaccine within 2 months of first dose of study drug.
4. History of hypersensitivity reaction, anaphylaxis or other clinically significant reactions or known allergy to any of the study drug ingredients.
5. History of transient ischemic attack or stroke or any unexplained loss of consciousness within 12 months of screening
6. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection upon admission to clinic on Day -1 (SARS-CoV-2 testing to be performed according to site standard process) or participant report of 'Long-COVID' any time prior to screening (where long-COVID is defined by probable or confirmed SARS-CoV-2 infection; usually within 3 months from the onset of COVID-19, with symptoms and effects that last for at least 2 months).

7. History of any clinically significant disorder (which, in the opinion of the Investigator [or delegate] would make implementation of the protocol or interpretation of study results difficult, or that would put the participant at risk by participating in the study), including cardiovascular (including but not limited to unstable angina, myocardial infarction, chronic heart failure), hematologic, pulmonary, hepatic, renal, gastrointestinal, connective tissue, uncontrolled endocrine/metabolic, oncologic (within the last 5 years), neurologic (including seizures, strokes, brain tumours), and psychiatric (including but not limited to major depression, schizophrenia, bipolar disorder, personality, or substance abuse disorder), or any disorder that may prevent the successful completion of the study or influence the absorption, distribution, metabolism, excretion, or action of the study drug.

   Note: Participants with well-controlled asthma (and is not receiving inhaled or oral steroids) is permitted, per PI (or delegate) discretion. Participants with well controlled, mild depression or anxiety, with no change in medication within the past 3 months is permitted, per PI (or delegate) discretion.

8. History of surgery or hospitalisation within 12 weeks prior to screening, or surgery planned during the study.
9. Lack of suitable veins for multiple venepunctures/cannulations as assessed by the Investigator or delegate at screening.
10. Presence of any tattoos or scarring which (in the opinion of the Investigator [or delegate]) would interfere with injection site reaction assessments.
11. Laboratory results at screening that indicate inadequate renal function (estimated creatinine clearance above the ULN or below the LLN, as calculated by the Cockcroft and Gault formula).
12. Liver function test results elevated more than 1.5-fold above the ULN for gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) or alanine aminotransferase (ALT). Volunteers with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the Investigator, if the levels are unaccompanied by clinical signs and are determined to be normal variants.
13. Liver function tests outside the normal range for bilirubin (more than 1.5-fold above the ULN for total bilirubin).
14. Any clinically relevant laboratory finding or medical condition that could place the volunteer at risk for participation in the study.
15. Any active infection requiring systemic antibiotic, antifungal, or antiviral medication within 14 days prior to first dose of study drug.
16. Concurrent enrolment in another clinical study, or participation in another clinical study within 90 days prior to screening.
17. Regular consumption of >10 standard alcoholic drinks/week where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc/Vol], 100 mL wine [12% Alc/Vol], 30 mL spirit [40% Alc/Vol]).
18. Positive alcohol breath test at screening or upon admission to the clinic on Day -1.
19. Positive urine drugs of abuse test at screening or upon admission to the clinic on Day -1.
20. Participant has a positive cotinine test upon admission to the clinic on Day -1.
21. Participant smokes more than 5 cigarettes or equivalent per week, and/or participant is unwilling to abstain from smoking for 72 hours prior to check-in on Day -1 and throughout the confinement period at the study site.
22. Use of cannabis or delta-9- tetrahydrocannabinol (THC), including for medicinal purposes, within 90 days prior to the start of the first dose of study drug, and/or participant is unwilling to abstain from use during the study
23. Participant is breastfeeding or pregnant, or planning to breastfeed or become pregnant during the study.
24. Known substance abuse or medical, psychological, or social conditions that, in the opinion of the PI (or delegate), may interfere with the participants inclusion in the clinical study or evaluation of the clinical study results.
25. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C (HepC) virus antibody, or human immunodeficiency (HIV) antibody tests at screening.
26. Participant has donated blood/blood products, experienced significant (> 500 mL) blood loss within 3 months prior to the first dose administration or receipt of a blood transfusion within 1 year prior to the first dose administration.
27. Any other condition or prior therapy that in the opinion of the Investigator (or delegate) would make the participant unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.

Additional Inclusion Criteria (Parkinson's Disease Participants)

Parkinson's Disease Participants will be included in the study only if they satisfy all the following criteria:

1. Diagnosis of Parkinson's disease as defined by:

• Evidence (written confirmation by a neurologist) of diagnosis of Parkinson's disease between 1-10 years prior to first dose administration.

Note: Criteria for diagnosis of Parkinson's disease is per the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease:

• Progressive asymmetric onset of bradykinesia

• Muscle rigidity and/or rest tremor (4- to 6-Hz tremor in the fully resting limb)

  • Hoehn and Yahr score of 1-3 (inclusive)
  • Not diagnosed with any other neurodegenerative diseases.
  • If on levodopa/carbidopa therapy: Stable levodopa/carbidopa therapy for at least 3 months prior to screening with ability to be withdrawn from therapy for at least 12 hours (e.g., overnight) prior to study drug administration and on-study assessments. Participants will be able to resume therapy immediately after study drug is administrated and on-study assessments are completed.
  • If not on levodopa/carbidopa therapy: To be able to remain treatment naïve throughout the study from screening through to the final EoS visit.

Additional Exclusion Criteria (Parkinson's Disease Participants)

Parkinson's Disease Participants will be excluded from the study if there is evidence of any of the following:

1. Use of antibiotics within 30 days prior to the start of the first dose of study drug.
2. Use of over-the-counter (OTC) prebiotics and probiotics supplements. Note: Participants receiving stable use of within 30 days prior to the start of the first dose of study drug may be permitted.
3. History of use of any biologic therapy targeting beta-amyloid peptides or tau protein.
4. History of any brain surgery for Parkinson's disease, or a history of focused ultrasound treatment at any time, or history of any neuromodulation procedures.
5. Unexplained falls (≥ 3 falls) within 12 months prior to the start of the first dose of study drug.
6. History of in situ prostate carcinoma.
7. History of any clinically significant disorder (which, in the opinion of the Investigator [or delegate] would make implementation of the protocol or interpretation of study results difficult, or that would put the participant at risk by participating in the study), including cardiovascular (including but not limited to unstable angina, myocardial infarction, chronic heart failure), hematologic, pulmonary, hepatic, renal, gastrointestinal, connective tissue, uncontrolled endocrine/metabolic, oncologic (within the last 5 years), neurologic (including seizures, strokes, brain tumours; but not including Parkinson's disease), and psychiatric (including but not limited to major depression, schizophrenia, bipolar disorder, personality, or substance abuse disorder), or any disorder that may prevent the successful completion of the study or influence the absorption, distribution, metabolism, excretion, or action of the study drug. Participants with diagnosed concomitant diseases and that are receiving stable therapy (for > 1 year prior to screening) may be permitted at the discretion of the PI (and in consultation with the Sponsor).

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
Experimental: Healthy Volunteers - SAD; Single dose of LBT-3627 administered to healthy volunteers	Drug: Placebo; Vehicle; Drug: LBT-3627; Synthetic peptide
Experimental: Parkinson's disease patients - SAD; Single dose of LBT-3627 administered to Parkinson's disease patients	Drug: Placebo; Vehicle; Drug: LBT-3627; Synthetic peptide
Experimental: Parkinson's disease patients - MAD; Multiple doses of LBT-3627 administered to Parkinson's disease patients	Drug: Placebo; Vehicle; Drug: LBT-3627; Synthetic peptide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence, nature, and severity of adverse events [Safety and Tolerability]	Day of treatment to end of follow-up period (1, 2 or 4 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration [Cmax]	The peak plasma concentration of a drug after administration.	Day of treatment to end of follow-up period (1, 2 or 4 weeks)
Elimination half life [T1/2]	The time required for the concentration of the drug to reach half of its original value.	Day of treatment to end of follow-up period (1, 2 or 4 weeks)
Time to reach Cmax [Tmax]	Time required to reach Cmax.	Day of treatment to end of follow-up period (1, 2 or 4 weeks)
Volume of Distribution [Vd]	The apparent volume in which a drug is distributed (i.e., the parameter relating drug concentration in plasma to drug amount in the body).	Day of treatment to end of follow-up period (1, 2 or 4 weeks)
Concentration [C]	Amount of drug in a given volume of plasma	Day of treatment to end of follow-up period (1, 2 or 4 weeks)
Area under the curve [AUC]	The integral of the concentration-time curve (after a single dose or in steady state).	Day of treatment to end of follow-up period (1, 2 or 4 weeks)
Clearance [CL]	The volume of plasma cleared of the drug per unit time.	Day of treatment to end of follow-up period (1, 2 or 4 weeks)
Bioavailability [f]	The systemically available fraction of a drug.	Day of treatment to end of follow-up period (1, 2 or 4 weeks)

Collaborators and Investigators

• Sponsor: Longevity Biotech Australia Pty Ltd (subsidiary)

Publications and helpful links

Helpful Links

• Michael J. Fox Trial Finder

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2024
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: June 10, 2024
• First Submitted That Met QC Criteria: June 13, 2024
• First Posted (Actual): June 20, 2024

Study Record Updates

• Last Update Posted (Actual): June 20, 2024
• Last Update Submitted That Met QC Criteria: June 13, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• 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: LBT-3627-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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