A Study of MA-0217 (ASP1128) in Healthy Adult Subjects an... | NCT04742517

Description Module

Label	Type	Description	Intervention Names
Single ascending dose of ASP1128	Experimental	Participants (6 for each cohort) will receive a single dose of ASP1128.	Drug: ASP1128
Single ascending dose of Placebo	Placebo Comparator	Participants (2 for each cohort) will receive a single dose of matching Placebo.	Drug: Placebo
Multiple ascending dose of ASP1128	Experimental	Participants (9 for each cohort) will receive daily doses of ASP1128 for 7 consecutive days.	Drug: ASP1128
Multiple ascending dose of Placebo	Placebo Comparator	Participants (3 for each cohort) will receive matching Placebo for 7 consecutive days.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
ASP1128	Drug	Intravenous	Multiple ascending dose of ASP1128 Single ascending dose of ASP1128

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of participants with Adverse Events (AEs) in Part 1	An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. In order to identify any events that may be associated with study procedures and could lead to a change in the conduct of the study, AEs will be collected even if the subject has not received study drug treatment.	Up to Day 16
Number of participants with laboratory value abnormalities and/or AEs in Part 1	Number of participants with potentially clinically significant laboratory values.	Up to Day 16
Number of participants with vital sign abnormalities and/or AEs in Part 1	Number of participants with potentially clinically significant vital sign values.	Up to Day 16
Number of participants with electrocardiogram (ECG) abnormalities and/or AEs in Part 1	Number of participants with potentially clinically significant 12-ECG values.	Up to Day 16
Number of participants with real-time cardiac monitoring (cardiac telemetry) abnormalities and/or AEs in Part 1	Number of participants with potentially clinically significant cardiac telemetry values.	On Day 1
Number of participants with AEs in Part 2	An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. In order to identify any events that may be associated with study procedures and could lead to a change in the conduct of the study, AEs will be collected even if the subject has not received study drug treatment.

Secondary Outcomes

Measure	Description	Time Frame
Part 1: Pharmacokinetics (PK) of ASP1128 in plasma: Area under the concentration-time curve (AUC) from the time of dosing extrapolated to time infinity (AUCinf)	AUCinf will be recorded from the PK plasma samples collected.	Up to 72 hours post-dose on Day 1
Part 1: PK of ASP1128 in plasma: AUC from the time of dosing to the last measurable concentration (AUClast)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

For adult subjects (cohorts 1.1 to 1.8 and cohorts 2.1 to 2.5):
- Subject is a healthy adult male or female subject 18 to 55 years of age, inclusive at screening.
- Subject has a body mass index (BMI) range of 18.5 to 32.0 kg/m^2, inclusive and weighs at least 50 kg at screening.
For elderly subjects (cohort 2.6):
- Subject is a healthy elderly male or female subject ≥ 65 years of age at screening.
- Subject has a BMI range of 18.5 to 32.0 kg/m^2, inclusive and weighs at least 50 kg at screening.
Subject is considered an adult according to local regulation at the time of signing informed consent.
Female subject must either be of nonchildbearing potential:
- Postmenopausal (defined as at least 1 year without any menses for which there is no other obvious pathological or physiological cause) prior to screening, or
- Documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy or bilateral oophorectomy), OR, if of childbearing potential:
- Agree not to try to become pregnant during the study and for 28 days after the final study drug administration
- Have a negative blood pregnancy test at screening and a negative urine pregnancy test on day -1
- If heterosexually active, agree to consistently use 1 form of highly effective birth control starting at screening and throughout the study period and for 28 days after the final study drug administration
Female subject must agree not to breastfeed starting at screening and throughout the study period and for 28 days after the final study drug administration.
Female subject must not donate ova starting at screening and throughout the study period and for 28 days after the final study drug administration.
A sexually active male subject with female partner(s) who is(are) of childbearing potential is eligible for the study if:
- Agree to use a male condom starting at screening and continue throughout study treatment and for 28 days after the final study drug administration.
- If the male subject has not had a vasectomy or is not sterile, their female partner(s) is(are) utilizing 1 form of highly effective birth control starting at screening and continue throughout study treatment and for 28 days after the male subject receives their final study drug administration.
Male subject must not donate sperm starting at screening and throughout the study period and for 28 days after the final study drug administration.
Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner(s) is(are) breastfeeding throughout the study period and for 28 days after the final study drug administration.
Subject agrees not to participate in another interventional study while participating in the present study.

Exclusion Criteria:

Subject has received investigational drug within 28 days or 5 half-lives, whichever is longer, prior to screening.
Subject has any condition which makes the subject unsuitable for study participation.
Female subject who has been pregnant within 6 months prior to screening or breastfeeding within 3 months prior to screening.
Subject has a known or suspected hypersensitivity to ASP1128 or any components of the formulation used.
Subject has had previous exposure with ASP1128.
Subject has unsuitable or difficult venous access to support the intravenous infusion(s) and/or required blood draws.
Subject has any of the liver function tests (LFTs; aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], gamma-glutamyl transferase and total bilirubin [TBL]) above the upper limit of normal (ULN) at screening or on day -1. In such a case, the assessment may be repeated once.
Subject has total creatine kinase (CK) > 1.5 × ULN or cardiac troponin I above the ULN at day -1.
Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies) prior to study drug administration.
Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal and/or other major disease or malignancy.
Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (noncutaneous) infection within 1 week prior to day -1.
Subject has any clinically significant abnormality following the physical examination, electrocardiogram (ECG) and protocol-defined clinical laboratory tests at screening or on day -1.
Subject has a mean pulse < 45 or > 90 bpm; mean systolic blood pressure (SBP) > 140 mmHg; mean diastolic blood pressure (DBP) > 90 mmHg (measurements taken in triplicate after subject has been resting in the supine position for at least 5 minutes; pulse will be measured automatically) at screening or on day -1. For elderly subjects the following criteria apply: SBP > 160 mmHg, DBP > 100 mmHg. If the mean blood pressure exceeds the limits above, 1 additional triplicate can be taken.
Subject has a mean QT interval using Fridericia's correction formula (QTcF) interval of > 430 msec (for males) and > 450 msec (for females) at screening or on day -1. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken.
Subject has used 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 acetaminophen (up to 2 g/day), hormonal contraceptives and hormone replacement therapy.
Subject has used any peroxisome proliferator-activated receptor (PPAR) ligands such as fibrates and thiazolidinediones, including self-medication obtained via the internet, in the 4 weeks prior to study drug administration.
Subject has smoked or has used tobacco-containing products and nicotine or nicotine-containing products in the past 6 months prior to screening.
Subject has a history of consuming > 14 units of alcoholic beverages per week within 6 months prior to screening or has a history of alcoholism or drug/chemical/substance abuse within past 2 years prior to screening (Note: 1 unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits/hard liquor) or the subject tests positive for alcohol or drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates) at screening or on day -1.
Subject has used any drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates) within 3 months prior to day -1.
Subject has used any inducer of metabolism (e.g., barbiturates and rifampin) in the 3 months prior to day -1.
Subject has had significant blood loss, donated ≥ 1 unit (450 mL) of blood or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to day -1.
Subject has a positive serology test for hepatitis B surface antigen (HBsAg), hepatitis B core (HBc) antibodies, hepatitis A virus (HAV) antibodies (immunoglobulin M [IgM]), hepatitis C virus (HCV) antibodies or antibodies to human immunodeficiency virus (HIV) type 1 and/or type 2 at screening.
Subject is an employee of Astellas, Mitobridge or designated contract research organization (CRO).