None listed
Conditions
Brief summary
The phase 1 trial will be conducted in two parts, initially, it will comprise of a single-centre, subject blinded randomised single ascending dose study of TIMP-GLIA to 6 cohorts. Each cohort will contain six participants two will be randomised to placebo and four to TIMP-GLIA. At the beginning of each dose level, one sentinel (TIMP-GLIA) participant and one placebo participant will be dosed. The remaining four participants will be dosed 48 hours after the sentinel participants. A Safety Committee will meet after the completion of each cohort dosing to ascertain safety prior to the next dose level is given. In the second part of the trial, a repeat dosing strategy will be employed (maximum, two doses seven days apart) at the Level 4 and Level 6 dose. Following a screening period (up to 28 days), eligible participants will be randomised to TIMP-GLIA or placebo using a computer generated randomisation schedule which will be held by an unblinded pharmacist.
Interventions
The study is a two-part design, the first part consisting of single ascending doses (SAD) of TIMP-GLIA (Gliadin, a glutenoid protein encapsulated in poly lactic-co-glycolic acid nanoparticles) or saline placebo delivered over a 30-minute controlled infusion under the supervision of study nurses, to 6 cohorts of 6 subjects. All subjects will be resident in the clinic for 48 hours after each dose for medical observation.
In each cohort one drug-treated (sentinel subject) and one placebo subject wi
The study is a two-part design, the first part consisting of single ascending doses (SAD) of TIMP-GLIA (Gliadin, a glutenoid protein encapsulated in poly lactic-co-glycolic acid nanoparticles) or saline placebo delivered over a 30-minute controlled infusion under the supervision of study nurses, to 6 cohorts of 6 subjects. All subjects will be resident in the clinic for 48 hours after each dose for medical observation. In each cohort one drug-treated (sentinel subject) and one placebo subject will be dosed first with the the remainder of the cohort (3 drug-treated and 1 placebo) to be dosed after 48 hours has elapsed. A Safety Management Committee (SMC) meeting will be held after completion of each cohort to review safety observations against predefined stopping rules before continuation to the next dose level. Cohort dosing is shown below: SAD Cohort 1 TIMP-GLIA 8 mg or saline placebo Cohort 2 TIMP-GLIA 40 mg or saline placebo Cohort 3 TIMP-GLIA 120 mg or saline placebo Cohort 4 TIMP-GLIA 300 mg or saline placebo Cohort 5 TIMP-GLIA 600 mg or saline placebo Cohort 6 TIMP-GLIA 800 mg or saline placebo In the second part of the study two further cohorts (n=6) will be given two doses of TIMP-GLIA, 7 days apart as follows: Level 4 dosing TIMP-GLIA 300 mg or saline placebo Level 6 dosing TIMP-GLIA 800 mg or saline placebo SMC review will occur between cohorts.
Sponsors
Delpharm Consultants Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. In the opinion of the investigator, the healthy subject is capable of understanding and complying with protocol requirements and agrees to comply with protocol requirements. 2. The healthy subject provides written informed consent to participate. 3. The healthy subject is an adult man or woman, 18 to 65 years of age, inclusive, at Screening Visit. 4. Has a minimum body weight greater than 45 kg up to a maximum body weight of 121 kg, inclusive, and if BMI is less than18 (classified as “underweight”) or greater than 25 (classified as “overweight”) is otherwise healthy in the opinion of the investigator. 5. If male, agrees to practice medically approved contraception that may include, but is not limited to, abstinence, monogamous relationship with a female who is not of child-bearing potential, surgical sterilization procedure (vasectomy), and or condoms throughout the study. 6. If female, is not of child bearing potential (postmenopausal or premenopausal with surgical sterilization) or agrees to practice medically approved contraception that may include, but is not limited to, abstinence, monogamous relationship with a male who is post-surgical sterilization procedure (vasectomy), or agrees to use medically acceptable and highly effective birth control methods (e.g., an intrauterine device, a double-barrier method such as condom and diaphragm, a contraceptive implant, injectable contraceptive, or oral contraceptive) throughout the study. 7. Agrees not to participate in another interventional study while participating in the present study.
Exclusion criteria
1. Has a history of clinically confirmed immunoglobulin E (IgE)-mediated reaction and/or anaphylaxis to wheat, barley or rye. 2. Has a known history of hypersensitivity or allergies to TIMP-GLIA components or any other known severe hypersensitivity or allergic reaction (any reaction that resulted in hospitalization [initial or prolonged], congenital anomaly, or disability, or that required medical intervention to prevent permanent impairment or damage) to any other allergens (medications, food or environmental). 3. Has any history or evidence of splenectomy (removal of the spleen) or any clinically significant cardiovascular, gastrointestinal endocrinologic, haematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease, in the opinion of the investigator. 4. Uses any prescribed or non-prescribed drugs (including vitamins, natural and herbal remedies, in the 2 weeks prior to study drug administration, except for occasional use of acetaminophen (up to 2 g/day) or PI-approved contraceptives or hormone replacement therapy. 5. Received immunosuppressive doses of corticosteroids (more than 20 mg of prednisone given daily for 2 weeks or more) within 2 months prior to Day 1, any dose of corticosteroids within 30 days of Day 1, or high dose inhaled corticosteroids greater than or equal to 960 µg/day of beclomethasone dipropionate or equivalent]) within 30 days of Day 1. 6. Has known human immunodeficiency virus (HIV) infection or positive for HIV antibodies at Screening. 7. Has a history of any acute illness including, fever greater than or equal to 38 degrees C) within 14 days of check-in Day -1. 8. Has an active malignancy, or history of malignancy or chemotherapy, within the past 5 years other than history of localized or surgical removal of focal basal cell skin cancer, cervical cancer in situ treated successfully in the past by local treatment or by hysterectomy. 9. Has known liver disease or serology positive for hepatitis C infection; positive hepatitis B surface antigen (HBsAg) at Screening Visit. 10. Has a positive test result for drugs of abuse in urine or alcohol in urine or breath at Screening Visit or at Check-in. 11. Has a history of any drug or alcohol abuse in the past 5 years, or alcohol consumption greater than 21 units per week that, in the opinion of the investigator, would interfere with the subject’s ability to comply with the study requirements.. Alcohol consumption will be prohibited 24 hours prior to entry into the clinical research unit until discharge. 12. Has the inability to undergo venepuncture or tolerate venous access as determined by the investigator or designee. 13. If female, is pregnant or lactating or intending to become pregnant before or during the study. 14. Has clinically significant laboratory results at Screening, as determined by the investigator, which are indicative of hepatic, renal or haematological disorders or other condition that would indicate the subject should not participate in the trial. 15. Has clinically significant, abnormal electrocardiogram (EGC) at Screening, as determined by the investigator. 16. Has received any investigational drug within 30 days or 5 half-lives prior to first dosing/Day 1. 17. Received a live or inactive vaccine within 28 days prior or a subunit vaccine within 14 days prior to first dosing/Day 1 or the subject has a planned vaccination during the study. 18. Has donated blood or plasma within 56 days prior to Screening and plans to donate blood or plasma within 5 weeks of completing the study. 19. Has received blood products, monoclonal antibody, or other systemic protein therapy within 6 months prior to first dosing/Day 1. 20. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study or may consent under duress. 21. Is unsuitable for enrolment in the opinion of the investigator for any other reason not specified above.
Outcome results
None listed