Clinical trial NCT05238493: A Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VEL-101
Official title: A Phase 1, Randomized, Double Blind, Placebo Controlled, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VEL-101 Administered Intravenously or Subcutaneously in Healthy Subjects.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Veloxis Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-02-14
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

Brief summary: This study is primarily designed to assess the safety and tolerability of single doses of VEL-101 when administered subcutaneously (via injection into an area under the skin) or intravenously (via infusion into a vein). As each new group of participants is enrolled into the study, the dose administered to that group may be higher than a previous dose shown to be safe in other participants. The study is also designed to determine blood levels of VEL-101 and some substances produced by the immune system following VEL-101 administration. This information can provide insight into how quickly VEL-101 is eliminated from the body and some if its effects on the body.


Eligibility criteria: Inclusion Criteria:

1. Able to understand the key components of the study as described in the written informed consent document, and willing and able to provide written informed consent;
2. Self-described healthy male or female, 18 to 65 years of age, inclusive, at Screening;
3. Body mass index (BMI) within the range of 18.5 to \<35 kg/m2 at Screening;
4. If female, is surgically sterile, 2 years postmenopausal, or, if of childbearing potential, is using a medically accepted method of contraception (abstinence, the simultaneous use of 2 barrier methods, or the use of an intrauterine device \[in place at least 3 months prior to dosing\], or oral contraceptives), and agrees to continued use of this method until study Day 50;
5. If male, agrees to use an approved method of contraception (abstinence, 2 barrier methods, female partner's use of an intrauterine device \[in place at least 3 months prior to dosing\], oral contraceptives or female partner who is surgically sterile or 2 years postmenopausal) and agrees to use this method until study Day 50;
6. Able to comply with all study procedures, including the required overnight stays in the clinical research center and the food, beverage, and medication restrictions during the study;
7. In the opinion of the Investigator, is able to adhere to the requirements of the study.

Exclusion Criteria:

1. Known allergy to study medication or its components (non-medicinal ingredients) or a history of a severe allergic reaction to any drug or history of multiple food/drug allergies;
2. Use of tobacco, smoking cessation products, or products containing nicotine within 3 months prior to Screening;
3. History of alcohol or illicit drug use disorder, marijuana consumption as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, or a reported habitual alcohol intake greater than 1.5 oz (ethanol equivalent) per day (eg, 24 oz of beer, 10 oz of wine, or 3 oz of hard liquor) for the past two years;
4. Positive urine screen for drugs of abuse including tetrahydrocannabinol or has a positive breathalyzer test on admission to the study center, at Screening and at Baseline for each treatment cohort;
5. Positive serologic test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV), or positive for EBV polymerase chain reaction \[PCR\] at Screening;
6. Negative for Epstein-Barr Virus (\[EBV\], viral capsid antigen \[VCA IgG\], Epstein-Barr nuclear antigen antibody \[EBNA\],);
7. History of inadequately treated active or latent mycobacterium tuberculosis (TB) infection or positive QuantiFERON® TB Gold at Screening;
8. History of diabetes, clinically significant cardiovascular, pulmonary, hepatic, renal, or malabsorptive disease, as determined by the Principal Investigator (PI);
9. Clinically significant abnormality upon physical examination at Screening, as determined by the Investigator;
10. Clinically significant abnormality on 12-lead ECG at Screening, as determined by the Investigator;
11. Clinically significant abnormal laboratory values (clinical chemistry, hematology, coagulation, or urinalysis) outside the reference values established by the laboratory, as determined by the Investigator at Screening;
12. Positive pregnancy test or lactating at Screening or at Day -1;
13. Participation in an investigational study within 30 days or within 5 half-lives of the investigational drug, whichever is longer, prior to the Screening Visit;
14. Receiving any antibody or biologic medicinal product within 90 days prior to Screening;
15. Blood or plasma donation within 72 hours prior to Screening or planned up to study Day 50;
16. Positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen testing or equivalent testing on Day -1; Subjects fully recovered from coronavirus disease 2019 (COVID-19) infection are eligible. Subjects with a past history of hospitalization due to COVID-19 infection will be excluded;
17. History of infection or vaccination within 90 days prior to the Screening, or planned vaccination within 90 days of dosing, with the exception of vaccination against SARS CoV-2;
18. History or presence, upon clinical evaluation, of any illness that, in the opinion of the Investigator, would interfere with the ability to provide informed consent or comply with study instructions, or that might confound the interpretation of the study results or put the subject at undue risk.

Primary outcomes:
measure: Number and Percentage of Participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 through Day 50
measure: Number and Percentage of Participants with Serious TEAEs
timeFrame: Day 1 through Day 50
measure: Number and Percentage of Participants with Grade 3 or Higher TEAEs
timeFrame: Day 1 through Day 50
measure: Number and Percentage of Participants with TEAEs Leading to Withdrawal from the Study
timeFrame: Day 1 through Day 50
measure: Number and Percentage of Participants with TEAEs Leading to Death
timeFrame: Day 1 through Day 50
Secondary outcomes:
measure: Number and Percentage of Participants with Abnormal Chemistry Panel Results
timeFrame: Days -1, 2 (24 hours), 3, 5, 8, 15, 22, 29, 50
measure: Number and Percentage of Participants with Abnormal Hematology Panel Results
timeFrame: Days -1, 2 (24 hours), 3, 5, 8, 15, 22, 29, 50
measure: Number and Percentage of Participants with Abnormal Coagulation Panel Results
timeFrame: Days -1, 2 (24 hours), 3, 5, 8, 15, 22, 29, 50
measure: Number and Percentage of Participants with Abnormal Urinalysis Results
timeFrame: Days -1, 2 (24 hours), 3, 5, 8, 15, 22, 29, 50
measure: Number and Percentage of Participants with Abnormal 12-lead Electrocardiogram (ECG) Results
timeFrame: Days 1 (0, 1, 2, 3, 4, 5, 8, 12, 12, 16, and 20 hours), 2 (24, 30, 36, and 42 hours), 3, 4, 5, 8, 29, 50
measure: Number and Percentage of Participants with Abnormal Vital Signs Results
timeFrame: Days -1, 1 (0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 8, 12, 16, 20 hours), 2 (24, 30, 36, 42 hours), 3, 4, 5, 6, 7, 8, 15, 22, 29, 50
measure: CD28 Receptor Occupancy
timeFrame: Day 1 (0, 1, 3, 5, 8 hours) and Days 2 (24 hours), 3, 15, 22, 29, 50
measure: Number and Percentage of Participants with Anti-drug Antibody (ADA) Formation
timeFrame: Days 1 (0 hour), 15, 29, 50
measure: Number and Percentage of Participants with Detectable Systemic Cytokine Concentrations
timeFrame: Day 1 (0, 1, 3, 5, 8 hours) and Days 2 (24 hours), 3, 15, 50
measure: Maximum Plasma Concentration (Cmax)
timeFrame: Day 1 (0, 1, 3, 5, 8 hours) and Days 2 (24 hours), 3, 4, 5, 6, 7, 8, 15, 22, 29, 50
measure: Time of Observed Maximum Plasma Concentration (Tmax)
timeFrame: Day 1 (0, 1, 3, 5, 8 hours) and Days 2 (24 hours), 3, 4, 5, 6, 7, 8, 15, 22, 29, 50
measure: Terminal Elimination Rate Constant
timeFrame: Day 1 (0, 1, 3, 5, 8 hours) and Days 2 (24 hours), 3, 4, 5, 6, 7, 8, 15, 22, 29, 50
measure: Terminal Elimination Half-life
timeFrame: Day 1 (0, 1, 3, 5, 8 hours) and Days 2 (24 hours), 3, 4, 5, 6, 7, 8, 15, 22, 29, 50
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) from Time Zero to Time of Last Observed Quantifiable Concentration
timeFrame: Day 1 (0, 1, 3, 5, 8 hours) and Days 2 (24 hours), 3, 4, 5, 6, 7, 8, 15, 22, 29, 50
measure: AUC from Time Zero to Infinity
timeFrame: Day 1 (0, 1, 3, 5, 8 hours) and Days 2 (24 hours), 3, 4, 5, 6, 7, 8, 15, 22, 29, 50
measure: Total Clearance (CL)
timeFrame: Day 1 (0, 1, 3, 5, 8 hours) and Days 2 (24 hours), 3, 4, 5, 6, 7, 8, 15, 22, 29, 50
measure: Terminal Volume of Distribution (Vz)
timeFrame: Day 1 (0, 1, 3, 5, 8 hours) and Days 2 (24 hours), 3, 4, 5, 6, 7, 8, 15, 22, 29, 50
measure: Bioavailability (F)
timeFrame: Day 1 (0, 1, 3, 5, 8 hours) and Days 2 (24 hours), 3, 4, 5, 6, 7, 8, 15, 22, 29, 50
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: CTI Clinical Research Center
state: Ohio
Study officials:
affiliation: Veloxis Pharmaceuticals
name: Libbie McKenzie, MD
role: STUDY_DIRECTOR
References: