Ulcerative Colitis (UC)
Conditions
Brief summary
This study with ALTB-268 will determine the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending doses of intravenously administrated ALTB-268 in healthy participants.
Detailed description
This is a Phase I, randomized, double-blind, single ascending dose (SAD) study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of intravenously administered ALTB-268 in healthy participants. Approximately 24 healthy participants will be recruited. The primary objective is to evalute the safety and tolerability of intravenous infusion of SAD in healthy participants. The secondary objectives are (1) to characterize the PK profile of ALTB-268 in plasma following single IV doses in healthy participants, and (2) to assess the PD of ALTB-268 following single IV doses in healthy participants.
Interventions
BIOLOGICALALTB-268
monoclonal antibody
OTHERPlacebo
Saline solution
Sponsors
AltruBio Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, non-smoker (no use of tobacco or nicotine products within 3 months prior to screening), ≥18 and ≤55 years of age, with body mass index (BMI) \>18.5 and \<32.0 kg/m2 and body weight ≥50.0 kg for males and ≥45.0 kg for females. 2. Healthy as defined by: 1. the absence of clinically significant illness and surgery within 4 weeks prior to dosing. 2. the absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic diseases. 3. Female participants of non-childbearing potential must be: 1. post-menopausal (spontaneous amenorrhea for at least 12 consecutive months prior to dosing) with confirmation by documented follicle- stimulating hormone (FSH) levels ≥40 mIU/mL; or 2. surgically sterile (bilateral oophorectomy, bilateral salpingectomy, hysterectomy, or bilateral tubal ligation) at least 3 months prior to dosing. 4. Able to understand the study procedures, agree to comply with all study visits, procedures, and restrictions, agree to comply with the prescribed dosage regimens and communicate to study personnel about AEs and concomitant medication use, and provide signed informed consent to participate in the study.
Exclusion criteria
1. Any clinically significant abnormal finding at physical examination at screening and/or Day -1. 2. Clinically significant abnormal laboratory test results at screening and/or Day -1; or positive serology test results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antigen and antibody, or QuantiFERON®-TB test at screening. 3. Any history of suicidal ideation as evidenced by answering "yes" to questions 4 or 5 on the suicidal ideation portion of the C-SSRS completed at screening, or any history of suicide attempts. 4. Any history of clinical depression. 5. C-SSRS score at Day -1 (baseline) above Type 1 ideation. 6. PHQ-8 total score ≥5 at screening and/or Day -1 (baseline).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the safety and tolerability of ALTB-268 following intravenous (IV) infusion in healthy participants - Adverse Events | Through study completion, up to day 71 of the study | \- Numbers of participants with adverse events (AEs): seriousness, severity, relationship to the investigational products, outcome, duration, and management |
| To evaluate the safety and tolerability of ALTB-268 following intravenous (IV) infusion in healthy participants - Infusion Site Assessments | Through study completion, up to day 71 of the study | \- Infusion site assessments, the extent of local reaction at the infusion site will be graded using the scores described below; a global severity rating for infusion site reactions will be included in the assessment of AEs. Infusion Site Reaction Score: None: No reaction; Mild: Tenderness with or without associated symptoms; Moderate: Pain; lipodystrophy; edema; phlebitis; Severe: Ulceration or necrosis; severe tissue damage; operative intervention indicated. |
| To evaluate the safety and tolerability of ALTB-268 following intravenous (IV) infusion in healthy participants - C-SSRS | Through study completion, up to day 71 of the study | \- Columbia suicidality severity rating scale (C-SSRS) is a suicidal ideation and behavior rating scale to evaluate suicide risk. |
| To evaluate the safety and tolerability of ALTB-268 following intravenous (IV) infusion in healthy participants - PHQ-8 | Through study completion, up to day 71 of the study | \- Patient Health Questionnaire-8 (PHQ-8) depression scale is used for depression screening and severity. |
| To evaluate the safety and tolerability of ALTB-268 following intravenous (IV) infusion in healthy participants - Clinical Laboratory Test | Through study completion, up to day 71 of the study | \- Clinical laboratory test results, including white blood cell, lymphocyte and neutrophail (cell counts/ul). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) of ALTB-268 AUC | Through study completion, up to day 71 of the study | * AUC0-t, area under the concentration-time curve from time 0 to t hours * AUC0-inf, area under the concentration-time curve from time 0 to infinity |
| Pharmacokinetic (PK) of ALTB-268 Cmax | Through study completion, up to day 71 of the study | Mmaximum concentration (Cmax) |
| Pharmacokinetic (PK) of ALTB-268 Tmax | Through study completion, up to day 71 of the study | Time to reach Cmax (Tmax) |
| Pharmacokinetic (PK) of ALTB-268 T½ | Through study completion, up to day 71 of the study | Terminal half-life (T½) |
| Pharmacokinetic (PK) of ALTB-268 CL | Through study completion, up to day 71 of the study | Total body clearance (CL) |
| Pharmacokinetic (PK) of ALTB-268 Vz | Through study completion, up to day 71 of the study | Volume of distribution (Vz) |
| Pharmacokinetic (PK) of ALTB-268 Vss | Through study completion, up to day 71 of the study | Steady-state volume of distribution (Vss) |
| Pharmacodynamics (PD) of ALTB-268 following single IV doses in healthy participants. | Through study completion, up to day 71 of the study | Levels of free soluble P-selectin glycoprotein ligand-1 (sPSGL-1) in plasma. |
| Immunogenicity of ALTB-268 in plasma following single IV doses in healthy participants | Through study completion, up to day 71 of the study | Incidence and level of anti-drug antibodies (ADAs). |
Countries
United States
Outcome results
None listed