Healthy
Conditions
Brief summary
This is a Phase 1, FIH, randomized, double-blind, placebo-controlled study designed to assess the safety, tolerability, PK and PD after SAD and MAD in healthy adult participants.
Detailed description
The present study is the first administration of ABL301 in humans. This study will evaluate safety and tolerability and characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile of ABL301, following IV single ascending dose (Part 1 - SAD), and multiple ascending dose (Part 2 - MAD) administrations, in healthy adult participants. In Part 1 SAD, seven single doses are planned to be administered in an ascending manner: DL1, DL2, DL3, DL4, DL5, DL6 and DL7. Each dose level will comprise 8 participants randomly assigned in an overall 6:2 ratio (ABL301:Placebo), including 1:1 ratio for the first 2 sentinel participants and 5:1 ratio for the remaining participants, to receive a single dose of study drug or placebo, respectively. In Part 2 MAD, three multiples doses are planned to be administered in an ascending manner: DL1, DL2 and DL3. Each dose level will comprise 10 participants randomly assigned in an overall 8:2 ratio (ABL301:Placebo)
Interventions
DRUGABL301
SAD: Participants will receive a single dose of ABL301 IV infusion, MAD: Participants will receive multiple doses of ABL301 IV infusion
DRUGPlacebo
SAD: single Placebo IV infusion, MAD: multiple Placebo IV infusion
Sponsors
ABL Bio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Single Ascending Dose and Multiple Ascending Dose
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* The participant is considered by the investigator to be in good health as determined by medical history, clinical laboratory test results (including urinalysis), physical and neurological examination, vital signs, and ECG. * The participant agrees to comply with all protocol requirements. * The participant is a healthy male or female 18 to 55 years of age, inclusive. * The participant has body weight ≥50 kg and a BMI of 19 to 30 kg/m2, inclusive.
Exclusion criteria
* The participant has a history of cardiovascular disease (eg, hypertension, arrhythmia, heart failure, long QT syndrome, or other conditions/diseases causing prolongation of the QT/QTcF). * The participant has a past medical history of clinically significant ECG abnormalities or a family history of a prolonged QT interval syndrome prior to initial dosing. * The participant has frequent headaches and/or migraine or recurrent nausea and/or vomiting (for vomiting only: more than twice a month). * The participant has history of malignancy including solid tumors and hematologic malignancies within 5 years prior to the screening visit (except basal cell and squamous cell carcinomas of the skin that had been completely excised and were considered cured). * The participant has a history of clinically significant drug or food allergies, as determined by the investigator. * (MAD only) The participant has a current psychiatric disorder, suicidal ideation in the previous 6 months (as assessed by the C SSRS), or a lifetime suicide attempt.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events | Day 1 to Day 113 for SAD Part and D1 to Day 169 for MAD Part | Number of participants with AEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of pharmacokinetic(PK) parameter Cmax in serum | Day 1 to Day 113 for SAD Part and D1 to Day 169 for MAD Part | Maximum plasma concentration observed |
| Assessment of pharmacokinetic(PK) parameter AUClast in serum | Day 1 to Day 113 for SAD Part and D1 to Day 169 for MAD Part | Area under the plasma concentration versus time curve from time zero to the real time tlast |
| Assessment of immunogenicity | Day 1 to Day 113 for SAD Part and D1 to Day 169 for MAD Part | Numbers of subjects with ADA(anti-drug antibody) positive |
| Assessment of pharmacokinetic(PK) parameter AUCtau in serum (MAD only) | D1 to Day 169 for MAD Part | Area under the serum concentration time curve over the dosing interval |
Other
| Measure | Time frame | Description |
|---|---|---|
| Total alpha-synuclein in plasma | Day 1 to Day 113 for SAD Part and D1 to Day 169 for MAD Part | Plasma samples for PD analysis of ABL301 will be collected |
Countries
United States
Outcome results
None listed