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

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)

The purpose is to study Safety and Tolerability.

Study Overview

• Status: Terminated
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: Saline 0.9%; Drug: SPC5001

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333
    • Centre for Huma Drug Research (CHDR)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. BMI of 18-33 kg/m2

3. 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:

1. 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.

2. Active acute or chronic infection, including, but not limited to: upper airway infection, urinary tract infection, and skin infection
3. 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.
4. 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.
5. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Santaris Pharma A/S
• Investigators: Principal Investigator: Koos Burggraaf, MD PhD, Centre for Human Drug Research (CHDR)

Publications and helpful links

General Publications

• van Poelgeest EP, Hodges MR, Moerland M, Tessier Y, Levin AA, Persson R, Lindholm MW, Dumong Erichsen K, Orum H, Cohen AF, Burggraaf J. Antisense-mediated reduction of proprotein convertase subtilisin/kexin type 9 (PCSK9): a first-in-human randomized, placebo-controlled trial. Br J Clin Pharmacol. 2015 Dec;80(6):1350-61. doi: 10.1111/bcp.12738. Epub 2015 Oct 24.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: May 5, 2011
• First Submitted That Met QC Criteria: May 9, 2011
• First Posted (Estimate): May 10, 2011

Study Record Updates

• Last Update Posted (Estimate): November 22, 2011
• Last Update Submitted That Met QC Criteria: November 21, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Keywords: PCSK9; HDL; hypercholesterolemia; hyperlipidemia; LDL; LNA-oligonucleotide
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: SPC5001-901; EudraCT 2011-000489-36