A Study of AST-008 in Healthy Subjects

A Randomized, Combined SAD/MAD Phase 1 Study of the Safety, Pharmacokinetics and Pharmacodynamics of AST 008 in Healthy Subjects

AST-008 will be dosed subcutaneously to healthy volunteers in a combined SAD/MAD study to evaluate its safety, tolerability, pharmacokinetics and pharmacodynamics.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer Study
• Intervention / Treatment: Drug: AST-008

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 1YR
    • Richmond Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

1. Healthy male or female subjects aged ≥18 and ≤40 years of age at the time of first dosing.
2. Subjects must have a body mass index (BMI) between 18.0-25.0 kg/m² inclusive.
3. Satisfactory medical assessment with no clinically significant or relevant abnormalities as determined by medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory evaluation (haematology, biochemistry, coagulation, and urinalysis) that is reasonably likely to interfere with the subject's participation in or ability to complete the study as assessed by the Investigator.
4. Ability to provide written, personally signed, and dated informed consent to participate in the study, in accordance with the ICH Good Clinical Practice (GCP) Guideline E6 (1996) and applicable regulations, before completing any study-related procedures.
5. An understanding, ability, and willingness to fully comply with study procedures and restrictions.

Main Exclusion Criteria:

1. Current or recurrent disease (e.g., cardiovascular, haematological, neurological, endocrine, renal, liver, GI or other conditions) that could affect the action, absorption, or disposition of AST-008, or could affect clinical assessments or clinical laboratory evaluations.
2. Any history of cancer.
3. Any history (including significant and confirmed family history) of autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, autoimmune hepatitis, or thrombocytopenia.
4. Has had an acute illness within two weeks prior to screening.
5. Current or relevant history of physical or psychiatric illness that may require treatment or make the subject unlikely to fully comply with the requirements of the study or complete the study, or any condition that presents undue risk from the investigational product or study procedures.
6. Any other significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study may influence the result of the study, or the subject's ability to participate in the study.
7. Female subjects who are pregnant or breastfeeding.
8. Subjects with abnormal findings of inguinal, axillary, or cervical lymph nodes at screening or Day -1.
9. A positive human immunodeficiency virus (HIV) antibody screen, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody screen.
10. Titres above reference ranges (according to local laboratory) for autoimmune antibodies: rheumatoid factor (RF), anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SCREENING
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single Ascending Dose	Drug: AST-008; AST-008 is a toll-like receptor 9 agonist.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious related adverse events	To evaluate SAEs after a single subcutaneous dose of AST-008	Up to 1 month after the last dose of AST-008
Adverse events	To evaluate adverse events after a single subcutaneous dose of AST-008	Up to 1 month after the last dose of AST-008

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose finding	To recommend a dose and regimen for further development.	Up to 1 month after the last dose of AST-008
Maximum plasma concentration assessment	Measurement of the maximum observed plasma concentration (Cmax) after single doses of AST-008	Up to 1 month after the last dose of AST-008
AUC assessment	Measurement of the area under the curve (AUC) after single doses of AST-008	Up to 1 month after the last dose of AST-008
Pharmacodynamics	Measurement of type 1 cytokine concentrations as a function of time after single doses of AST-008	Up to 1 month after the last dose of AST-008
Pharmacodynamics	Measurement of changes in absolute number and and fraction of a panel of lymphocyte markers as a function of time after single doses of AST-008	Up to 1 month after the last dose of AST-008
QTc interval testing	To determine the effect of AST-008 on QTc interval	Up to 1 month after the last dose of AST-008

Collaborators and Investigators

• Sponsor: Exicure, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 20, 2017
• Primary Completion (ACTUAL): August 16, 2018
• Study Completion (ACTUAL): August 16, 2018

Study Registration Dates

• First Submitted: March 10, 2017
• First Submitted That Met QC Criteria: March 15, 2017
• First Posted (ACTUAL): March 22, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 25, 2018
• Last Update Submitted That Met QC Criteria: September 21, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: AST-008-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes