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

NCT01350960 | Terminated Phase 1

• 2 other identifiers: SPC5001-901EudraCT 2011-000489-36
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose is to study Safety and Tolerability.

Conditions

Hypercholesterolemia

Keywords

hypercholesterolemia; hyperlipidemia; LDL; HDL; PCSK9; LNA-oligonucleotide

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (6)

saline 0.9%

PLACEBO COMPARATOR

Drug: Saline 0.9%

Cohort 1

EXPERIMENTAL

0.5 mg/kg in Healthy Subjects

Drug: SPC5001

Cohort 2

EXPERIMENTAL

1.5 mg/kg in Healthy subjects

Drug: SPC5001

Cohort 3

EXPERIMENTAL

5.0 mg/kg in Healthy subjects

Drug: SPC5001

Cohort 4

EXPERIMENTAL

10 mg/kg in Healthy subjects

Drug: SPC5001

Cohort 5

EXPERIMENTAL

TBD mg/kg in FH subjects

Drug: SPC5001

Interventions

SPC5001 DRUG

3 weekly SC injections

Cohort 1

Saline 0.9% DRUG

3 weekly SC injections

saline 0.9%

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Santaris Pharma A/S: lead

Study Sites (1)

Centre for Huma Drug Research (CHDR)

Leiden, 2333, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 26261033 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia; Hyperlipidemias

Interventions

SPC5001; Sodium Chloride

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Koos Burggraaf, MD PhD

  Centre for Human Drug Research (CHDR)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2011
• First Posted: May 10, 2011
• Study Start: May 1, 2011
• Primary Completion: October 1, 2011
• Study Completion: November 1, 2011
• Last Updated: November 22, 2011

Record last verified: 2011-11

Locations

NL (1)