A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of NJA-730 in Healthy Volunteers
- Conditions
- Acute graft-versus-host disease (aGvHD)Inflammatory and Immune System - Other inflammatory or immune system disorders
- Registration Number
- ACTRN12618001428257
- Lead Sponsor
- apaJen Pharma Inc.
- Brief Summary
56 subjects in SAD and 16 in MAD were treated in the FIH study. No Adverse event(AEs), Severe adverse event(SAEs), Dose Level Toxicity(DLTs), or Treatment-Emergent Adverse Event(TEAEs) leading to study drug withdrawal or premature withdrawal were observed; majority of TEAEs were Grade 1/Mild in severity. No dose-dependence noted in incidence of AEs and ADRs, no ADRs related to liver and kidney function or inflammatory disorders were observed, and all AEs were transient. Most frequent ADRs in active were lymphadenopathy, headache, and diarrhea (4.8% each) in SAD. In MAD, most frequent ADRs were headache (25%), upper respiratory tract infection, dizziness, and lethargy (8.3% each). However, AEs such as lymphadenopathy, headache, upper respiratory tract infection, and dizziness were also observed in placebo. No safety problematic AEs were observed for Clinical Labs, Vital Signs, ECG, and physical examination. NJA-730 concentration peaks were observed near or at the end of infusion followed by rapid elimination. No accumulation was observed following multiple administration. An approximately proportional increase was observed across the dose range following both SAD and MAD doses. In conclusion, safety results indicate no safety concerns for NJA-730 up to 0.6mg in both SAD and MAD which were well tolerated in healthy volunteers. Similar results were obtained in an extension study with high doses up to 6mg, and data is currently being aggregated.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Male
- Target Recruitment
- 96
A subject will be eligible for study participation if he meets all of the following criteria:
1. Healthy males aged between 18 and 55 years at time of informed consent
2. BMI of 18 kg/m2 to less than or equal to 30 kg/m2 (both inclusive)
3. A resting pulse greater than or equal to 40 bpm and less than or equal to 100 bpm at screening and on Day -1.
4. A resting systolic blood pressure of less than or equal to 140 mmHg and a resting diastolic blood pressure of less than or equal to 90 mmHg at screening and on Day -1.
5. Baseline laboratory test values within reference ranges based on the blood and urine samples taken at screening and on Day -1. Out of normal ranges values may be accepted by the Investigator, if not clinically significant.
6. Non-smoker and/or casual smoker who uses no more than 10 cigarettes (or equivalent quantity of any other nicotine containing products eg, cigars, chewing tobacco, snuff, etc.) per week. Subject must abstain from smoking 3 days prior to admission and throughout the confinement period, and test negative on Day -1 for urine cotinine test. Subject must also abstain from smoking 72 hours prior to each outpatient visit.
7. Male subjects with female partners of childbearing potential must agree to use barrier contraception (i.e. condom) and their female partners must use a highly effective method of contraception (i.e. hormonal contraceptives, or intrauterine contraception) from screening through 90 days after the last dose of study drug. Male subjects who are not sexually active (i.e. abstinent) will not be required to use a contraceptive method unless they become sexually active. Males must also refrain from donating sperm during the study and for 90 days post end of study.
8. Ability to understand and voluntarily give informed consent to communicate well with the Investigator, in the local language, to understand and comply with the requirements of the study and to have signed an informed
consent form in accordance with institutional and regulatory guidelines
9. Ability to remain in the study center for a 4-day period.
10. The subject is, in the opinion of the Investigator,
generally healthy based on assessment of medical history, physical examination, vital signs, electrocardiogram (ECG), and the results of the hematology, clinical chemistry, urinalysis, serology, and other laboratory tests.
A subject will be ineligible for study participation if he meets any of the following criteria:
1. The subject has a history or presence of any clinically significant immunological disorder/disease (such as allergy, atopy, autoimmune diseases, etc.), cardiovascular, thromboembolic events, respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological (particularly diabetes or pre-diabetes), hematological, dermatological, venereal, neurological, chronic infectious or psychiatric disease or other major disorder. A history of childhood asthma, hay fever or mild eczema may be acceptable at the discretion of the investigator.
2. History of cancer, including any form of skin cancer, which has not been in remission for at least 5 years prior to the first dose of study product.
3. History of abdominal surgery (excluding laparoscopic cholecystectomy or uncomplicated appendectomy) or thoracic or non-peripheral vascular surgery within 6 months prior to the first dose of study product.
4. Current history of asthma and any skin disease. A history of childhood asthma or mild eczema may be acceptable at the discretion of the investigator.
5. The subject's corrected QT interval (QTcF) (Fridericia's correction) is >450 ms at screening and on Day -1. An out-of-range or abnormal ECG should be repeated. In total, 3 ECGs should be recorded consecutively, and the Investigator must evaluate the triplicate ECG. If the subject's QTcF is >450 ms on at least 2 ECGs, the subject must be excluded.
6. Prior exposure to NJA-730 or any other systemic immunosuppressive agent in the last 6 months or 5 half-lives (whichever is longer).
7. The subject has taken prescription or non-prescription medication, herbal remedies, vitamins or minerals within 2 weeks prior to the first dose of study product (or within 5 half-lives prior to the first dose of study product for any
medication ingested, whichever is longer) without approval of the Investigator, NapaJen representative and medical monitor.
8. The subject has taken any investigational products within 30 days prior to the first dose of study product or 5 halflives, whichever is longer. Unless the investigational product is an immunosuppressive agent in which case prior exposure considered is in the last 6 months according to exclusion criteria number 6.
9. The subject has a history of significant hypersensitivity or anaphylaxis involving any drug, food or other precipitating agent (e.g. bee sting).
10. The subject has any abnormal laboratory values that, in the opinion of the primary Investigator, are deemed clinically significant and would preclude participation in the study.
11. The subject has any concurrent illness that may affect the
particular target or absorption, distribution, and elimination of the study product.
12. The subject has had a clinically significant illness within 4 weeks prior to the first dose of study product.
13. Any major surgery or trauma with significant blood loss within the last 3 months prior to the first dose of study product.
14. Blood donation of 500 mL within 3 months prior to the first dose of study product.
15. Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (anti-HCV) at screening.
16. Any history of tuberculosis (TB), whether treated or untreated (and/or a positive QuantiFERON®-TB Gold blood test).
17. Chest x-ray undertaken 3 months prior to screen or at screening showing signs of
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method