A Phase I Randomised, Double Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Effect of Food on the Bioavailability of SKY-0515 in Healthy Volunteers and Patients with Huntington’s Disease

Phase 1

Recruiting

• Conditions: Huntington’s Disease; Human Genetics and Inherited Disorders - Other human genetics and inherited disorders

• Registration Number: ACTRN12624000602527
• Lead Sponsor: Skyhawk Therapeutics, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-05-09
• Last Update Posted: 26 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 74

Inclusion Criteria

Part C (i):
1. Must have given written informed consent
2. Males and females, aged between 25 and 65 years.
3. Confirmed diagnosis of HD as defined by:
a. Genetically confirmed HD diagnosis by direct DNA testing. CAG repeat length greater than or equal to 40, and
b. Huntington’s Disease Integrated Staging System (HD-ISS) Stage 1: CAG greater than or equal to 40 & biomarker of pathogenesis. Atrophy identified in caudate volumetric magnetic resonance imaging (vMRI) and putamen vMRI, or
c. HD-ISS Stage 2: CAG greater than or equal to 40 & biomarker of pathogenesis & sign/symptom. Total Motor Score (TMS) greater than 6; Independence Score (IS) equal to 100 and Total Functional Capacity (TFC) equal to 13, or
d. HD-ISS Stage 3 (Mild): CAG greater than or equal to 40 & biomarker of pathogenesis & sign/symptom & functional change. TMS greater than 6, IS greater than or equal to 70, and TFC greater than or equal to 8.

Part C (ii):
1. Must have given written informed consent
2. Males and females, aged between 25 and 65 years.
3. Must have completed Part C (i) of the study.
4. Confirmed diagnosis of HD as defined by:
a. Genetically confirmed HD diagnosis by direct DNA testing. CAG repeat length greater than or equal to 40, and
b. Huntington’s Disease Integrated Staging System (HD-ISS) Stage 1: CAG greater than or equal to 40 & biomarker of pathogenesis. Atrophy identified in caudate volumetric magnetic resonance imaging (vMRI) and putamen vMRI, or
c. HD-ISS Stage 2: CAG greater than or equal to 40 & biomarker of pathogenesis & sign/symptom. Total Motor Score (TMS) greater than 6; Independence Score (IS) equal to 100 and Total Functional Capacity (TFC) equal to 13, or
d. HD-ISS Stage 3 (Mild): CAG greater than or equal to 40 & biomarker of pathogenesis & sign/symptom & functional change. TMS greater than 6, IS greater than or equal to 70, and TFC greater than or equal to 8.
5. Participant is otherwise medically healthy (in the opinion of the Investigator), as
determined by pre-study medical history and without clinically significant (CS) abnormalities including:
a. Physical examination without any clinically relevant findings
b. Systolic blood pressure in the range of 90 to 160 mmHg (inclusive) and diastolic blood pressure in the range of 50 to 95 mmHg (inclusive) after 5 minutes in supine or semi-supine position.
c. Heart rate in the range of 45 to 100 beats/minute (inclusive) after 5 minutes rest in supine or semi-supine position.
d. Body temperature (tympanic), between 35.5°C and 37.7°C (inclusive).
e. ECG without CS abnormal including QTcF lesser than 450 msec for male subjects and lesser than 470 msec for female subjects.
f. No CS findings in serum chemistry, haematology, coagulation or urinalysis (in the opinion of the Investigator).
g. Neutrophil count greater than or equal to 2x10^9/L, platelets count greater than or equal to 150x10^9/L and reticulocyte count greater than or equal to 0.2% of total red blood cells count.
6. Female participants must be of non-child-bearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy or 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 FSH level consistent with postmenopausal status, per local laboratory guidelines), or, if of child-bearing potential:
a. Must have a negative serum pregnancy test at the screenin

Exclusion Criteria

No exclusion criteria for Part C (i).

Part C (ii):
Huntington’s Disease patients will be excluded from Part C (ii) of the study if there is evidence of any of the following:
1. Any active infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications.
2. Suffers from frequent or recurrent infections (defined as greater than or equal to 3 recurrent or separate occurrences in the 12 months preceding first study drug administration or 2 recurrent or separate occurrences in the 6 months preceding first study drug administration).
3. Active malignancy and/or any history of malignant disease in the last 5 years (excludes surgically resected skin squamous cell or basal cell carcinoma or low grade cervical intraepithelial neoplasia).
4. Evidence of clinically relevant immunosuppression, including (but not limited to), immunodeficiency conditions such as common variable hypogammaglobulinemia.
5. History of hypersensitivity reaction, anaphylaxis or other clinically significant (CS) reactions or known allergy to the study drug or its ingredients.
6. Presence or history of cardiovascular disease (including unstable angina, myocardial infarction, chronic heart failure).
7. History of any CS disorder, including haematologic, pulmonary, hepatic, renal, GI, connective tissue disease, uncontrolled endocrine/metabolic, oncologic (within the last 5 years), neurologic (including seizures, strokes, brain tumours), and psychiatric diseases, 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 history of resolved childhood asthma, history of migraine (if lesser than or equal to 1 monthly episode and not on preventative medication), or history of non-hospitalised depression (if not on any anti-depressant) will be allowed to participate in the study.
8. Presence or having sequelae of GI, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs (prior gall bladder and/or appendix removal is not exclusionary if the procedure was undertaken greater than or equal to 3 months prior to study drug administration; if less than 3 months, history of such procedures may still be considered not exclusionary if it is deemed appropriate by the Investigator).
9. History of surgery or hospitalisation within 12 weeks prior to screening, or surgery planned during the study.
10. Are a suicide risk, as determined by meeting any of the following criteria:
a. Suicide attempt within one year prior to screening
b. Suicidal ideation as defined by a positive response to Question 5 on the C-SSRS (Baseline Visit Form) at screening
c. Presence or previous history of uncontrolled major depression
d. Significant suicide risk, per Investigator discretion.
11. Have marked cognitive impairment with a Montreal Cognitive Assessment (MoCA) score lesser than or equal to 22.
12. Presence of CS psychosis and/or confusional states, in the opinion of the Investigator.
13. Lack of suitable veins for multiple venepunctures/cannulations as assessed by the Investigator or delegate at screening and Day 1 (pre-dose)
14. Participant has donated blood/blood products or experienced significant blood loss within 3 months prior to the first dose administration.
15. Laboratory results at screening that indicate inadequate renal function (esti

Study & Design

• Study Type: Interventional
• Study Design: Not specified