Multiple Ascending Dose Study of SPC5001 in Treatment of Healthy Subjects and Subjects With FH

Study Overview
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Brief Summary
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The purpose is to study Safety and Tolerability.

Official Title
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A First-in-Human (FIH), Randomized, Dose-Escalation, Double-Blind, Placebo-Controlled Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SPC5001 Administered to Healthy Subjects and Subjects With Familial Hypercholesterolemia (FH)

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: SPC5001
* Drug: Saline 0.9%
* Drug: SPC5001
* Drug: SPC5001
* Drug: SPC5001
* Drug: SPC5001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects and subjects with heterozygous Familial Hypercholesterolemia Healthy male or female subjects, age 18 to 65 years, inclusive will be enrolled in Cohorts 1 through 4. In Cohort 5, male or female subjects with heterozygous Familial Hypercholesterolemia, confirmed through genetic testing, without a history of cardiovascular disease (e.g. coronary artery, peripheral artery or cerebrovascular disease), hypertension or diabetes mellitus age 18-45 years, inclusive, will be enrolled. BMI of 18-33 kg/m2 Screening hematology, clinical chemistries, coagulation and urinalysis consistent with overall good health and the following criteria are met: LDL ≥.3.24 mmol/L (≥ 100 mg/dL) Triglycerides (fasted) < 4.5 mmol/L (< 398 mg/dL) ALT within normal limits for healthy subjects and ALT < 2 x ULN for FH subjects Exclusion Criteria: Any uncontrolled or active major systemic disease including, but not limited to: cardiovascular, pulmonary, gastrointestinal, metabolic, urogenital, neurological, immunological, psychiatric, or neoplastic disorder with metastatic potential - History or presence of malignancy within the past year is an exclusion criterion. Subjects who have been successfully treated with no recurrence of basal cell carcinoma of the skin or carcinoma in-situ of the cervix may be enrolled. Active acute or chronic infection, including, but not limited to: upper airway infection, urinary tract infection, and skin infection Use of prescription medication within 14 days prior to the planned first drug administration and throughout the study. For the FH subjects statin therapy (and other lipid lowering therapies) will be prohibited within 4 weeks prior to the first study drug administration. Use of non-prescription or over-the-counter medications is prohibited within 7 days prior to the planned first drug administration and throughout the study. This includes all vitamins, herbal supplements, or remedies. An exception can be made for medication or supplements that in the opinion of both the investigator and the Sponsor do not complicate or compromise the study or interfere with the study objectives. Positive results on the following Screening laboratory tests: urine or serum pregnancy test (women only), alcohol breath test, urine drugs of abuse, hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: saline 0.9%<br> | Drug: Saline 0.9%<br>* 3 weekly SC injections<br>|
| Experimental: Cohort 1<br>0.5 mg/kg in Healthy Subjects | Drug: SPC5001<br>* 3 weekly SC injections<br>|
| Experimental: Cohort 2<br>1.5 mg/kg in Healthy subjects | Drug: SPC5001<br>* 3 weekly SC injections<br>|
| Experimental: Cohort 3<br>5.0 mg/kg in Healthy subjects | Drug: SPC5001<br>* 3 weekly SC injections<br>|
| Experimental: Cohort 4<br>10 mg/kg in Healthy subjects | Drug: SPC5001<br>* 3 weekly SC injections<br>|
| Experimental: Cohort 5<br>TBD mg/kg in FH subjects | Drug: SPC5001<br>* 3 weekly SC injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | Safety evaluation will assess adverse event (AE) profile, clinical laboratory safety tests, vital signs and ECG monitoring | Regularly over 78 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) of SPC5001 |  | up to 78 days | 
| Lipid lowering effect |  | Through out the study | 
| Area under the plasma concentration versus time curve (AUC) of SPC5001 |  | up to 78 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypercholesterolemia, hyperlipidemia, HDL, LDL, PCSK9, LNA-oligonucleotide