Multiple Ascending Dose Study of SPC4955 in Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to study safety and tolerability of SPC4955 in healthy subjects.

Official Title
-----------------
A First-in-Human (FIH), Randomized, Dose-Escalation, Double-Blind, Placebo-Controlled Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SPC4955 Administered to Healthy Subjects

Conditions
-----------------
Hypercholesterolemia

Intervention / Treatment
-----------------
* Drug: SPC4955
* Drug: SPC4955
* Drug: SPC4955
* Drug: SPC4955
* Drug: SPC4955
* Drug: Saline 0.9%


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male or female subjects, age 18-65 years, inclusive. BMI 18-33 kg/m2 Screening hematology, clinical chemistries, coagulation and urinalysis consistent with overall good health and the following criteria are met: LDL-C ≥3.24 mmol/L (≥125 mg/dL) Triglycerides (fasted) <2.7mmol/L (<239 mg/dL) ALT within normal limits 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. Subjects who have been successfully treated (for 3 months or longer) 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. 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. Positive results on the following Screening laboratory tests: urine 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
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>0.25 mg/kg in Healthy Subjects | Drug: SPC4955<br>* 3 Weekly SC injections<br>|
| Experimental: Cohort 2<br>0.5 mg/kg in Healthy Subjects | Drug: SPC4955<br>* 3 Weekly SC injections<br>|
| Experimental: Cohort 3<br>1.0 mg/kg in Healthy Subjects | Drug: SPC4955<br>* 3 Weekly SC injections<br>|
| Experimental: Cohort 4<br>1.5 mg/kg in Healthy Subjects | Drug: SPC4955<br>* 3 Weekly SC injections<br>|
| Experimental: Cohort 5<br>2.0 mg/kg in Healthy Subjects | Drug: SPC4955<br>* 3 Weekly SC injections<br>|
| Placebo Comparator: Saline 0.9%<br> | Drug: Saline 0.9%<br>* 3 Weekly SC injections<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects experiencing adverse events |  | up to 78 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) of SPC4955 |  | Up to 78 Days | 
| total Cholesterol |  | up to 78 days | 
| Area under the plasma concentration versus time curve (AUC) of SPC4955 |  | Up to 78 days | 
| LDL |  | up to 78 days | 
| HDL |  | up to 78 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
LDL, Hypercholesterolemia, HDL, apoB, hyperlipidemia, LNA-oligonucleotide