A Phase 1 Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ASP6294 Administered Intravenously or Subcutaneously in Healthy Young Male and Female Subjects
Overview
- Phase
- Phase 1
- Intervention
- ASP6294 Intravenous
- Conditions
- Healthy Subjects
- Sponsor
- Astellas Pharma Europe B.V.
- Enrollment
- 74
- Locations
- 1
- Primary Endpoint
- Safety of ASP6294 as assessed by Nature, frequency and severity of Adverse Events (AEs)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
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.
Detailed Description
The study consists of two parts: Part 1 (ascending intravenous dose) and Part 2 (ascending subcutaneous dose). Subjects will participate in either Part 1 or Part 2. Subjects in Part 1 and Part 2 will have a residential period of 6 days followed by outpatient visits.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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-
- •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).
Arms & Interventions
Part 1: ASP6294 Single Ascending Intravenous Doses
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.
Intervention: ASP6294 Intravenous
Part 1: ASP6294 Single Ascending Intravenous Doses
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.
Intervention: Placebo Intravenous
Part 2: ASP6294 Single Ascending Subcutaneous Doses
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.
Intervention: ASP6294 Subcutaneous
Part 2: ASP6294 Single Ascending Subcutaneous Doses
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.
Intervention: Placebo Subcutaneous
Outcomes
Primary Outcomes
Safety of ASP6294 as assessed by Nature, frequency and severity of Adverse Events (AEs)
Time Frame: Up to 120 Days
Safety of ASP6294 as assessed by Vital signs
Time Frame: Up to 120 Days
Vital signs include blood pressure, pulse and oral body temperature
Safety of ASP6294 as assessed by Neurological examination
Time Frame: Up to 120 Days
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".
Safety of ASP6294 as assessed by laboratory tests
Time Frame: Up to 120 Days
Laboratory tests include hematology, biochemistry and urinalysis
Safety of ASP6294 as assessed by routine 12-lead Electrocardiogram (ECG)
Time Frame: Up to 120 Days
Safety of ASP6294 as assessed by continuous cardiac monitoring (Holter ECG) (part 1 only)
Time Frame: Days 1 and 2
ECGs are to be collected using a 12-lead ECG continuous monitoring and recording system.
Safety of ASP6294 as assessed by Sensory assessments
Time Frame: Up to 120 Days
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.
Secondary Outcomes
- 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)
- Pharmacokinetics of ASP6294: CL/F (part 2 only)(Up to 120 Days)
- Pharmacokinetics of ASP6294: λz(Up to 120 Days)
- Pharmacokinetics of ASP6294: MRT(Up to 120 Days)
- Pharmacokinetics of ASP6294: tmax(Up to 120 Days)
- Pharmacokinetics of ASP6294: t1/2(Up to 120 Days)
- Pharmacokinetics of ASP6294: Vss (part 1 only)(Up to 120 Days)
- Pharmacokinetics of ASP6294: Vz (part 1 only)(Up to 120 Days)
- Pharmacokinetics of ASP6294: Vz/F (part 2 only)(Up to 120 Days)
- Pharmacodynamics of ASP6294 Nerve growth factor (NGF) total serum concentration: Cmax(Up to 120 Days)
- Pharmacodynamics of ASP6294 NGF total serum concentration: tmax(Up to 120 Days)