Phase 1 First-in-human Study Involving Healthy Subjects
Conditions
Brief summary
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TNX-1500 in Healthy Subjects
Interventions
DRUGTNX-1500
The active ingredient is an anti-CD154 humanized IgG4 monoclonal antibody.
DRUGPlacebo: USP 0.9% sterile saline for injection
The placebo comparator arm (Arm 4)
BIOLOGICALKeyhole Limpet Hemocyanin (KLH)
KLH is not the primary therapeutic drug being tested. Instead, it is an "immunogenic T-cell dependent antigen" used as a challenge tool to assess the pharmacological and immunosuppressant effects of TNX-1500
Sponsors
Tonix Pharmaceuticals, Inc.
CTI Clinical Trial and Consulting Services, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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. 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 ≤34.9 kg/m2 at Screening 4. if female, is surgically sterile, 1-year postmenopausal (confirmed by follicle stimulating hormone \[FSH\] at Screening), or, if of childbearing potential, is using a medically accepted method of contraception (the simultaneous use of 2 barrier methods, or the use of a non-hormonal intrauterine device \[IUD; in place at least 3 months prior to dosing\]) and agrees to continued use of this method until study Day 120 5. if male, agrees to use an approved method of contraception (2 barrier methods, female partner's use of an IUD \[in place at least 3 months prior to dosing\], oral contraceptives, or female partner who is surgically sterile or 2 years postmenopausal) and agrees to use this method until study Day 120 6. proof of receiving either Pfizer-BioNTech (COMIRNATY®) or Moderna (SPIKEVAXTM) coronavirus disease 2019 (COVID-19) vaccination ≥14 days prior to consent 7. able to comply with all study procedures, including the Clinical Research Center COVID-19 policy and procedures, required overnight stay in the Clinical Research Center, and the food, beverage, and medication restrictions during the study 8. in the opinion of the Investigator, is able to adhere to the requirements of the study.
Exclusion criteria
1. history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins, mAbs, or allergy to any of the TNX-1500 components 2. history of shellfish allergy 3. increased risk for thromboembolic events due to an ongoing heart disease or due to a medical device, including but not limited to vascular graft, valvular heart disease, atrial fibrillation, or a heart rhythm disorder 4. use of any hormonal replacement therapy or oral, transdermal, IUD, or injectable hormonal contraception 5. history of confirmed venous thromboembolism, arterial thrombosis, coagulopathy, or known platelet disorders 6. history of diabetes, clinically significant and currently relevant cardiovascular, pulmonary, hepatic, or kidney diseases, as determined by the Investigator 7. history of protein C or protein S deficiency disorders and/or clinically significant abnormality in protein C and protein S levels at Screening 8. requiring treatment with antiplatelet and/or antithrombotic drugs 9. received any doses of Janssen/Johnson \& Johnson COVID-19 vaccine 10. history of major surgery in the last 6 months or plans to undergo elective surgery during the study period 11. clinically significant abnormality upon physical examination at Screening, as determined by the Investigator 12. use of tobacco, smoking cessation products, or products containing nicotine within 3 months prior to Screening 13. history of alcohol or illicit drug use disorder, marijuana use disorder 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 14. positive urine screen for drugs of abuse including but not limited to tetrahydrocannabinol, or elevated ethanol breathalyzer concentration on admission to the study center at Screening or at Check-in (Day -1) 15. positive serologic test for hepatitis B surface antigen, hepatitis B core antibody, hepatitis C virus antibody, human immunodeficiency virus 16. negative for EBV viral capsid antigen IgG, Epstein-Barr nuclear antigen IgG 17. history of positive tuberculin (TB) test or positive QuantiFERON® TB Gold at Screening 18. clinically significant abnormality on 12-lead ECG at Screening, as determined by the Investigator 19. 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 or at Check-in (Day -1) 20. positive pregnancy test for women of childbearing potential (WOCBP) or lactating at Screening or at Check-in (Day -1) 21. 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 22. receiving any antibody or biologic medicinal product within 90 days prior to Screening 23. unable to refrain from or anticipates the use of any prescription and/or non-prescription medications, vitamins, herbal, or dietary supplements beginning 14 days prior to the first dose of study medication and throughout the study, with the exception of occasional 'as-needed' use of acetaminophen at a dose of ≤1000 mg/day 24. COVID-19 infection within 28 days prior to Check-in (Day -1) and/or a positive test for severe acute respiratory syndrome coronavirus 2 antigen testing or equivalent testing at Check-in (Day -1) 25. previous exposure to KLH 26. history of vaccination (with the exception of COVID-19 vaccination) within 60 days prior to the Screening, or anticipated need for any type of vaccination(s) and/or boosters (including COVID-19 booster) throughout the study 27. 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. 28. abnormal renal function (FDA, 2020) (Appendix 2) based on an estimated glomerular filtration rate (eGFR; CKD-EPI 2021 equation) (National Kidney Foundation, 2021) \< 60 mL/min at screening or at Check-in (Day -1). 29. moderate to severe hepatic impairment as per the Child-Pugh system (FDA, 2003) (Appendix 3). Exclude if Child-Pugh system score is \> 6 points based on: encephalopathy grade; level of ascites; serum bilirubin, mg/dL; serum albumin, g/dL; and prothrombin time, sec prolonged. Note: elevated bilirubin due to Gilbert's syndrome is not exclusionary.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Nature, frequency, and severity of treatment-emergent adverse events (TEAEs) | From enrollment to the end of the study at Day 120 |
Secondary
| Measure | Time frame |
|---|---|
| Cmax: maximum observed TNX-1500 serum concentration | From enrollment to the end of the study at Day 120 |
| Tmax: time to maximum TNX-1500 serum concentration | From enrollment to the end of the study at Day 120 |
| T1/2,z: Terminal exponential half-life, calculated as ln(2)/λz | From enrollment to the end of the study at Day 120 |
| AUC0-t: Area under the TNX-1500 serum concentration-time curve calculated using linear trapezoidal rule from time zero to time t, where t is the time of the last observed quantifiable concentration (Ct) | From enrollment to the end of the study at Day 120 |
| AUC0-∞: area under the TNX-1500 serum concentration-time curve from time zero to infinity, defined as AUC0-t + Ct/λz | From enrollment to the end of the study at Day 120 |
Countries
United States
Outcome results
None listed