None listed
Conditions
Brief summary
This study will assess the safety and tolerability of a single dose of Erwinaze, and how this drug acts in the body in healthy volunteers. Erwinaze is indicated for use in patients with acute lymphoblastic leukemia (blood cancer), but a trial of the drug in healthy volunteers is needed to obtain additional information to potentially make Erwinase available in more countries. Who is it for? You may be eligible for this study if you are aged 18 to 40 years and are in good general health without a clinically significant medical history. People who have been diagnosed with cancer will not be eligible for this study. Study details All participants who choose to enrol in this study will be screened for eligibility within the 28 days prior to being admitted to a clinical research unit for up to 5 days. Eligibility will be confirmed within the 24 hours prior to participants receiving a single intramuscular (injected) dose of Erwinaze. Participants will then be asked to provide a series of blood and urine samples to assess the effect of the drug on their body. After 5 days, participants will be discharged home and will be asked to attend two further study visits to provide blood samples. It is hoped this research will determine whether Erwinaze can be safely administered without causing severe reactions. Once the safety and tolerability of Erwinaze has been determined, further studies to assess the effect of Erwinaze in people with leukemia may proceed.
Interventions
This is a study of pharmacokinetics, safety, tolerability and pharmacodynamics of a single dose of Erwinaze in healthy participants. 12 participants will receive 25,000 U/m2 of Erwinaze.
Eligibility will be assessed during a screening period of up to 28 days prior to dosing. For the treatment period, subjects will be admitted to the clinical research unit (CRU) one day prior to the dosing (Day -1). Dosing of eligible participants will occur on the morning of dosing (Day 1).
On Day 1, all subject
This is a study of pharmacokinetics, safety, tolerability and pharmacodynamics of a single dose of Erwinaze in healthy participants. 12 participants will receive 25,000 U/m2 of Erwinaze. Eligibility will be assessed during a screening period of up to 28 days prior to dosing. For the treatment period, subjects will be admitted to the clinical research unit (CRU) one day prior to the dosing (Day -1). Dosing of eligible participants will occur on the morning of dosing (Day 1). On Day 1, all subjects will receive the calculated intramuscular dose of Erwinaze administered by a study nurse or doctor qualified to administer Intramuscular injections. Participants will be discharged from the clinic on Day 5 after all required study procedures are completed and if deemed medically fit. Subjects will return to the clinic on Day 8 (± 1 day), Day 15 (± 2 days) and Day 30 (± 2 days) for follow up visits. Additional follow-up visits may occur at discretion of the Principal Investigator.
Sponsors
Porton Biopharma Limited
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. The participant must be in good general health, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, safety laboratory tests and cardiac monitoring at screening and before administration of Erwinaze. 2. The participant must weigh more or equal to 50.0 kg and less or equal to 120.0 kg and have a body surface area less or equal to 2.0 m2 at screening and on Day -1. 3. The participant must have clinical laboratory values within the limit of normal as specified by the testing laboratory at Screening and Day -1, unless deemed not clinically significant by the PI or if specified by protocol restrictions. 4. The participant must have normal vital signs after more or equal to 5 minutes resting supine: a. More than 90.0 mmHg and less than 140.0 mmHg systolic blood pressure b. More than 50.0 mmHg and less than 95.0 mmHg diastolic blood pressure c. more than 45.0 bpm and less than 100.0 bpm heart rate d. Body temperature more or equal to 35.5 and less than 37.5°C. 5. The participant must have a standard 12-lead electrocardiogram (ECG) parameters after more or equal to 5 minutes resting in supine position with PR more or equal to 120.0 ms and less or equal to 220.0 ms, QRS less than 120.0 ms, QTcF less or equal to 450.0 ms for males and less or equal to 470.0 ms for females, and otherwise normal ECG, unless deemed not clinically significant by the PI. Eligibility should be assessed based on average of triplicate assessments. 6. The participant must have a negative urine drug screen and alcohol breath test at screening and at time of admission to the CRU (on Day -1). A positive drug or alcohol screen test result may be verified by re-testing (up to 1 false positive result permitted) and may be followed up at the discretion of the PI. 7. The participant must have the ability and willingness to attend the necessary visits to the CRU. 8. The participant must sign a written informed consent prior to undergoing any of the study-specific procedures, including screening procedures. 9. Females must not be pregnant nor lactating, and either surgically sterile since at least 90 days prior to screening (eg, tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or, if women of childbearing potential (WOCBP) engaged in a sexual relationship with a fertile male partner, use highly effective double barrier contraceptive method as assessed by the PI (condom AND a vaginal ring or a non-hormonal intrauterine device [IUD]) from screening until study completion, for at least 90 days after the administration of study drug, or be post-menopausal for more or equal to 12 months. Post-menopausal status will be confirmed through testing of follicle-stimulating hormone (FSH) per testing laboratory standards at screening for amenorrheic female participants. Females who are abstinent from heterosexual intercourse as part of their usual lifestyle and are not planning to conceive will be eligible for participation and are not required to use contraception. 10. WOCBP must have a negative pregnancy test at screening and admission and be willing to have additional pregnancy tests as required throughout the study. 11. Males must be surgically sterile (participants provide confirmation of the lack of viable sperm prior to screening), abstinent, or if engaged in a sexual relationship with a WOCBP, the participant and his partner must use an acceptable, highly effective, double barrier contraceptive method as assessed by the PI from screening until study completion, including the follow-up period, for at least 90 days after the administration of study drug. Acceptable methods of contraception include the use of condoms in combination with the use of an effective contraceptive for the female partner (WOCBP). Male participants whose female partner is post-menopausal, and participants who are abstinent from heterosexual intercourse as part of their usual lifestyle will be eligible and are not required to use contraception. 12. Male participants must agree to refrain from donating sperm from screening until study completion, including the follow-up period, for at least 90 days after the last dose of study drug. 13. The participant must be either non-smoker (have last smoked more than 30 days prior to screening and no longer smoking, or have never smoked), or smoke no more than the equivalent of 5 cigarettes per day since at least 30 days prior to screening. If user of other nicotine products (ie, spray, patch, e-cigarette) no more than the equivalent of 5 cigarettes per day since at least 30 days prior to screening is allowed. The participant must agree to abstain from smoking while in the CRU.
Exclusion criteria
1. Participant with medical history of or a positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), hepatitis B core antigen (HbcAg) or hepatitis C virus (HCV) antibodies at screening. 2. The participant has previously been exposed to treatment with any form of L-asparaginase. 3. The participant has a current and/or past history of pancreatitis or hepatitis. 4. The participant has a current and/or past history of haemorrhagic or severe thrombotic events. 5. The participant has hyperammonemia at screening. 6. The participant is immunocompromised as a result of conditions and/or treatments. 7. The participant has an absolute neutrophil count less than 1500/microliter at screening or on Day -1. 8. The participant is unsuitable for the intramuscular (IM) injection of Erwinaze and the evaluation of its safety and tolerability (eg, the presence of tattoos or scarring) at either the right or the left ventrogluteal site, as defined by the PI (or qualified designee). 9. The participant has any underlying physical or psychological medical condition that, in the opinion of the PI, would make it unlikely for them to complete the study. 10. The participant has evidence and/or history of blood clotting abnormalities and/or coagulopathies. 11. The participant has evidence or history of any current chronic medical condition (eg, hypertension, elevated cholesterol/triglycerides, asthma, or diabetes). 12. The participant uses or is planning to use any analgesic (with the exception of paracetamol/acetaminophen up to 3000 mg per day), antibiotic, antifungals, acetylsalicylic acid (aspirin), systemic steroids, and/or any nonsteroidal anti-inflammatory drugs (NSAIDs) within 28 days prior to the initial study drug administration and/or any other prescription or over the counter (OTC) medicines (with the exception of oral contraceptives) within 7 days prior to the initial study drug administration, unless in the opinion of the PI, local medical monitor (MM) and sponsor representative (must be a physician) the medication will not interfere with the study procedures or compromise participant safety. 13. The participant uses or is planning to use hormone replacement therapy (HRT) medications within 30 days following Erwinaze administration, and/or has used HRT within 30 days or 5 half-lives prior to Erwinaze administration, whichever is greater. 14. The participant has aspartate aminotransferase (AST) and/or alanine transaminase (ALT) levels that are more than the upper limit of normal (ULN) at screening or on Day -1. 15. The participant has an estimated glomerular filtration rate (GFR, calculated with the CKI-EPI) less or equal to 90.0 mL/min at screening or on Day -1. 16 The participant has amylase levels and/or lipase levels that are above the ULN at screening or on Day -1. 17. The participant has any of the standard coagulation blood parameters at screening and on Day -1 that are out of normal range, and/or the participant has protein C activity, protein S activity, and/or anti-thrombin III levels that are out of normal range at screening. 18. The participant has fasting glucose levels outside of the normal range, per testing laboratory standards at screening or on Day -1. 19. The participant has a total bilirubin above the ULN at screening or on Day -1. Participants with Gilbert’s syndrome are excluded from this study. 20. The participant has a history of or current alcoholism or drug abuse within the 1 year prior to the initial study drug administration. Alcohol abuse is defined as more than10 standard drinks per week. 21. The participant has donated whole blood (more than 499 mL), has had a significant blood loss (more than 499 mL) within 30 days prior to the initial study drug administration, or has donated plasma within 2 weeks prior to the initial study drug administration. 22. The participant has been dosed in a clinical study within 30 days before the initial administration of the study drug; used any experimental therapy within 30 days or 5 half-lives prior to the initial administration of the study drug, whichever is greater; or used any biologic therapy within 12 weeks or 5 half-lives prior to the initial administration of the study drug, whichever is greater. 23. The participant has had any clinically significant surgery within the 3 months prior to the initial study drug administration that is determined by the PI to have a potential impact on study participation. 24. The participant has an active infection (diagnosed or suspected), and/or history of recurrent infection (local or systemic) within 30 days prior to the initial study drug administration. 25. The participant has any acute and clinically relevant illness within 30 days prior to the initial study drug administration. 26. The participant has any known history of severe allergic, anaphylactic, or other hypersensitivity reactions to the study drug or its excipients, or a history of drug or other allergies including severe allergic reactions that in the opinion of the PI, contraindicates their participation in the study. 27. The participant has been judged by the PI to be unfit to participate for any other reason.
Outcome results
None listed