A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ASP6294 Administered Intravenously or Subcutaneously in Healthy Young Male and Female Subjects

NCT02681861 | Completed Phase 1 DMC

• 2 other identifiers: 6294-CL-00012014-003451-59
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of single ascending intravenous doses and single subcutaneous (sc) doses of ASP6294 in healthy young male and female subjects. This study will also evaluate the pharmacokinetics (pk) of single ascending intravenous doses and single ascending sc doses of ASP6294; determine the effect of ASP6294 administered intravenously and sc on the serum levels of circulating total Nerve Growth Factor (NGF); explore a potential gender difference in safety, tolerability and pk of single intravenous dose and single sc doses administrations of ASP6294 as well as determine the maximum tolerated dose (MTD) of single intravenous doses and single sc doses of ASP6294. Part 2 will also evaluate the relative bioavailability of ASP6294 when administered sc.

Conditions

Healthy Subjects; Pharmacokinetics of ASP6294

Keywords

Pharmacodynamics; Pharmacokinetics; ASP6294; Maximum tolerated dose; Healthy subjects

Outcome Measures

Primary Outcomes (7)

• Safety of ASP6294 as assessed by Nature, frequency and severity of Adverse Events (AEs)

  Up to 120 Days

• Safety of ASP6294 as assessed by Vital signs

  Vital signs include blood pressure, pulse and oral body temperature

  Up to 120 Days

• Safety of ASP6294 as assessed by Neurological examination

  Neurological Assessment will be measured on a scale for the following Neurological examinations: Gait; Coordination; Speech; Cranial Nerves; Sensations; Muscle Strength; Muscle Tone; Muscle Movement and Reflexes and will be rated as "Normal" or "Abnormal".

  Up to 120 Days

• Safety of ASP6294 as assessed by laboratory tests

  Laboratory tests include hematology, biochemistry and urinalysis

  Up to 120 Days

• Safety of ASP6294 as assessed by routine 12-lead Electrocardiogram (ECG)

  Up to 120 Days

• Safety of ASP6294 as assessed by continuous cardiac monitoring (Holter ECG) (part 1 only)

  ECGs are to be collected using a 12-lead ECG continuous monitoring and recording system.

  Days 1 and 2

• Safety of ASP6294 as assessed by Sensory assessments

  Sensory Assessment will be measured on a scale for Lower Limbs and Hands. The following categories: Touch Pressure; Pinprick; Vibration and Joint Position will be rated as Normal (=0 points), Decreased (= 1 point) or Absent (=2 points). A total score for the left and right side of lower limbs and hands will be calculated.

  Up to 120 Days

Secondary Outcomes (15)

• Pharmacokinetics of ASP6294: AUClast

  Up to 120 Days

• Pharmacokinetics of ASP6294: AUC168h

  Up to 120 Days

• Pharmacokinetics of ASP6294: AUCinf

  Up to 120 Days

• Pharmacokinetics of ASP6294: Cmax

  Up to 120 Days

• Pharmacokinetics of ASP6294: CL (part 1 only)

  Up to 120 Days

Study Arms (2)

Part 1: ASP6294 Single Ascending Intravenous Doses

EXPERIMENTAL

A dose escalation design will be implemented. Successive cohorts of patients (8 participants/cohort) will each be started on a fixed dose of ASP6294 or Placebo intravenously. If no dose limiting toxicities are observed escalation to the next higher dose is planned approximately every 3 weeks. Within the planned dose range, a dose lower than the next planned dose may be tested, or a dose level may be repeated, depending on emerging safety, tolerability and/or other relevant data, such as available pharmacokinetic and pharmacodynamic data of previous dose levels.

Drug: ASP6294 Intravenous; Drug: Placebo Intravenous

Part 2: ASP6294 Single Ascending Subcutaneous Doses

EXPERIMENTAL

A dose escalation design will be implemented. Successive cohorts of patients (8 participants/cohort) will each be started on a fixed dose of ASP6294 or Placebo subcutaneously. The subcutaneous cohorts may be done in parallel with part 1, using doses which have been proven to be safe and tolerable. Within the planned dose range, a dose lower than the next planned dose may be tested, or a dose level may be repeated, depending on emerging safety, tolerability and/or other relevant data, such as available pharmacokinetic and pharmacodynamic data of previous dose levels.

Drug: ASP6294 Subcutaneous; Drug: Placebo Subcutaneous

Interventions

ASP6294 Intravenous DRUG

Intravenous (IV)

Part 1: ASP6294 Single Ascending Intravenous Doses

ASP6294 Subcutaneous DRUG

Subcutaneous (SC)

Part 2: ASP6294 Single Ascending Subcutaneous Doses

Placebo Intravenous DRUG

Intravenous (IV)

Part 1: ASP6294 Single Ascending Intravenous Doses

Placebo Subcutaneous DRUG

Subcutaneous (SC)

Part 2: ASP6294 Single Ascending Subcutaneous Doses

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject has a body mass index range of 18.5 - 30.0 kg/m2, inclusive, and the subject weighs at least 50 kg (at screening).
• Female subject must either:
• Be of non-childbearing potential: Post-menopausal (defined as at least 1 year without any menses) prior to screening, or Documented surgically sterile
• Or, if of childbearing potential: Agree not to try to become pregnant during the study and for 120 days after final study drug administration; Must have a negative pregnancy test at screening and day -1; And, if heterosexually active, agree to consistently use 2 forms of birth control starting at screening and throughout the clinical study period and for 120 days after final study drug administration.
• Female subject must agree not to breastfeed starting at screening and throughout the clinical study period, and for 120 days after final study drug administration.
• Female subject must not donate ova starting at screening and throughout the clinical study period, and for 120 days after final study drug administration.
• Male subject and their female spouse/partner who are of childbearing potential must be using a highly effective form of birth control† in combination with a barrier method starting at screening and throughout the clinical study period and for 120 days after final study drug administration.
• Male subject must not donate sperm starting at screening and throughout the clinical study period and for 120 days after final study drug administration.
• Subject agrees not to participate in another interventional study during participation in the present study, defined as signing the informed consent form until completion of the last study visit.

You may not qualify if:

• Female subject who has been pregnant within 6 months prior to screening assessment or breast feeding within 3 months prior to screening.
• Subject has a known or suspected hypersensitivity to ASP6294 or any components of the formulation used.
• Subject has been exposed to a biological drug within the last 6 months prior to screening.
• Subject has a history of allergic or anaphylactic reaction to a biological drug.
• Subject has been diagnosed with osteoarthritis (OA) or has a history of rapidly progressive OA.
• Subject has any of the liver function tests (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], alkaline phosphatase, gamma glutamyl transferase, total bilirubin \[TBL\]) above the upper limit of normal (ULN) at day-1. In such a case, the assessment may be repeated once.
• Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
• Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic (including orthostatic hypotension and autonomic neuropathy), dermatologic, psychiatric, renal and/or other major disease or malignancy, as judged by the investigator.
• Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (noncutaneous) infection within 1 week prior to day -1 (admission day).
• Subject has any clinically significant abnormality following the investigator's review of the physical examination, ECG and protocol-defined clinical laboratory tests at screening or day -1.
• Subject has a mean pulse \< 40 or \> 90 beats per minute; mean systolic blood pressure \> 140 mmHg; mean diastolic blood pressure \> 90 mmHg (vital sign measurements taken in triplicate after subject has been resting in supine position for 5 minutes; pulse will be measured automatically) at screening and day -1. If the mean blood pressure exceeds the limits above, 1 additional triplicate measurement can be taken.
• Subject has a mean corrected QT interval using Fridericia's formula (QTcF) of \> 430 ms for males and \> 450 ms for females at screening and day -1. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken (admission day).
• Subject uses any prescribed or nonprescribed drugs (including vitamins, natural and herbal remedies, e.g. St. John's Wort) in the 2 weeks prior to study drug administration, except for occasional use of paracetamol (up to 2 g/day) or the use of contraceptives or hormone replacement therapy.
• Subject has a history of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to admission to the clinical unit.
• Subject has a history of drinking more than 21 units (male subjects) or 14 units (female subjects) of alcohol per week (1 unit = 10 g pure alcohol = 250 mL of beer \[5%\] or 35 mL of spirits \[35%\] or 100 mL of wine \[12%\]) within 3 months prior to admission to the clinical unit or the subject tests positive for alcohol or drugs of abuse at screening or day-1 (amphetamines, barbiturates, benzodiazepines, tetrahydrocannabinoids, cocaine, and opiates).

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead

Study Sites (1)

Site GB44001

Harrow, HA1 3UJ, United Kingdom

Location

Study Officials

• Executive Director

  Astellas Pharma Europe B.V.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2016
• First Posted: February 15, 2016
• Study Start: January 1, 2016
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: January 10, 2017

Record last verified: 2017-01

Locations

GB (1)