None listed
Conditions
Brief summary
SUN-001 is a drug being developed as a potential treatment for idiopathic pulmonary fibrosis (IPF). IPF is a chronic progressive Interstitial Lung Disease, the cause of which is unknown. IPF is associated with declining lung function and progressive respiratory failure. SUN-001 is expected to slow fibrosis progression and improve clinical outcomes in patients with IPF. In this study, we will look at the safety and tolerability of SUN-001. This study will also determine the levels of SUN-001 in the bloodstream when SUN-001 is given by nebuliser.
Interventions
The study is a randomized, double-blind, placebo-controlled, single and multiple ascending dose study of inhaled SUN-001 in healthy adult volunteers.
The study is comprised of two parts as follows:
*Part A – up to three planned and one optional, sequentially run, single ascending dose (SAD) cohorts
*Part B - up to two planned and one optional, sequentially run, multiple ascending dose (MAD) cohorts
The study will be initiated with the first SAD dose level cohort in Part A. The first MAD dose le
The study is a randomized, double-blind, placebo-controlled, single and multiple ascending dose study of inhaled SUN-001 in healthy adult volunteers. The study is comprised of two parts as follows: *Part A – up to three planned and one optional, sequentially run, single ascending dose (SAD) cohorts *Part B - up to two planned and one optional, sequentially run, multiple ascending dose (MAD) cohorts The study will be initiated with the first SAD dose level cohort in Part A. The first MAD dose level cohort in Part B (Cohort B1) can commence after initiation of Part A, however, the dose of SUN-001 tested will not be greater than the highest dose that has been declared as safe and well tolerated by the study Safety Monitoring Committee (SMC), based on all available data and cumulative clinical experience with SUN-001.SUN-001 drug product is supplied as a sterile aqueous solution formulated for inhalation. SUN-001 will be diluted in sterile normal saline (sodium chloride 0.9 percent) and administered via nebulization. The nebulizer is a small handheld device that produces a fine mist that is inhaled by mouth through a small mouthpiece, During this time, the participant will breathe normally. The duration of nebulization and dosing may vary depending on the participant’s respiratory rate and lung volume, but the total duration of inhalation procedure will not exceed 20 minutes. A single dose of SUN-001 for SAD cohorts will be administered in the morning on Day 1. For MAD cohorts, SUN-001 will be administered once daily in the morning from Day 1 through Day 14. Every effort will be made to administer the drug at approximately the same time every day. Part A of the study will evaluate up to three planned and one optional SAD cohorts (1 cohort per dose level). Eight participants will be enrolled into each cohort and randomly assigned to receive either placebo (n=2) or SUN-001 (n=6). The planned dose for cohort A1 is 0.6mg, with subsequent dose levels determined by the SMC. The maximum dose for Part A is 1.2mg and the maximum dose of Part B is 1mg daily for 14 days. Participants will only be able to participate once, in either Part A or Part B.
The study is a randomized, double-blind, placebo-controlled, single and multiple ascending dose study of inhaled SUN-001 in healthy adult volunteers.
The study is comprised of two parts as follows:
*Part A – three sequentially run, single ascending dose (SAD) cohorts were dosed as part of in the original protocol design. Amendment 1 added two sequentially run, single ascending dose (SAD) cohorts.
*Part B - up to two planned and one optional, sequentially run, multiple ascending dose (MAD) cohort
The study is a randomized, double-blind, placebo-controlled, single and multiple ascending dose study of inhaled SUN-001 in healthy adult volunteers. The study is comprised of two parts as follows: *Part A – three sequentially run, single ascending dose (SAD) cohorts were dosed as part of in the original protocol design. Amendment 1 added two sequentially run, single ascending dose (SAD) cohorts. *Part B - up to two planned and one optional, sequentially run, multiple ascending dose (MAD) cohorts. Amendment 1 added one multiple ascending dose (MAD) cohort. The study will be initiated with the first SAD dose level cohort in Part A. The first MAD dose level cohort in Part B (Cohort B1) can commence after initiation of Part A, however, the dose of SUN-001 tested will not be greater than the highest dose that has been declared as safe and well tolerated by the study Safety Monitoring Committee (SMC), based on all available data and cumulative clinical experience with SUN-001.SUN-001 drug product is supplied as a sterile aqueous solution formulated for inhalation. SUN-001 will be diluted in sterile normal saline (sodium chloride 0.9 percent) and administered via nebulization. The nebulizer is a small handheld device that produces a fine mist that is inhaled by mouth through a small mouthpiece, During this time, the participant will breathe normally. The duration of nebulization and dosing may vary depending on the participant’s respiratory rate and lung volume, but the total duration of inhalation procedure will not exceed 20 minutes. A single dose of SUN-001 for SAD cohorts will be administered in the morning on Day 1. For MAD cohorts, SUN-001 will be administered once daily in the morning from Day 1 through Day 14. Every effort will be made to administer the drug at approximately the same time every day. Part A of the study will evaluate up to three planned and one optional SAD cohorts (1 cohort per dose level). Eight participants will be enrolled into each cohort and randomly assigned to receive either placebo (n=2) or SUN-001 (n=6). The dose administered for cohort A1 was 0.6mg. Dose administered for cohort A2 was 0.9mg and A3 was 1.2mg. The planned dose for A4 is 2.4mg and A5 is 3.6mg. Progression between the dosing cohorts will require all available safety data to be reviewed by the safety monitoring committee (SMC) and the escalation approved. Part B of the study dosed two multiple ascending dose (MAD) cohorts. The dose in Cohort B1 was 0.5mg daily for 14 days and cohort B2 was 1.0mg daily for 14 days. The planned dose for cohort B3 is 3.0mg daily for 14 days. Cohort B3 will not commence until SAD cohort A5 has completed and all available safety and pharmacokinetic data has been reviewed by the SMC. Participants will only be able to participate once, in either Part A or Part B.
Sponsors
Sunterra Bio
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
To be eligible for this study, a participant must meet all of the following criteria: 1. Healthy adults equal to or greater than 18 and equal to or less than 60 years (inclusive). 2. Forced Expiratory Volume in one second (FEV1) equal to or greater than 80% predicted at the screening visit. 3. Body Mass Index (BMI) equal to or greater than 18 and equal to or less than 32 kg/m^2 (inclusive). 4. Females must be non-pregnant and non-lactating, and must be a) Surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before screening), or use highly effective contraceptive method (oral contraceptive pills [OCPs], long-acting implantable hormones, injectable hormones, a vaginal ring or an intrauterine device [IUD], or having undergone tubal occlusion at least 6 weeks prior to screening) and condom for male partner, from screening until study completion, including the follow-up period for at least 30 days after the last dose of study drug, or b) Post-menopausal for equal to or greater than12 months. Post-menopausal status will be confirmed through testing of follicle-stimulating hormone (FSH) levels (equal to or greater than40 IU/mL) at screening for amenorrheic female participants. Female participants who’s only partner has had a vasectomy (>30 days since vasectomy with no viable sperm), and female participants who are abstinent from heterosexual intercourse as part of their usual lifestyle will also be eligible for participation. 5. Women of childbearing potential (WOCBP) must agree to abstain from egg donation through 30 days after 5 half-lives of the study product have elapsed from the last dose of study drug. 6. Males must be: a) Surgically sterile (>30 days since vasectomy with no viable sperm), abstinent, or their partner must be surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or if engaged in sexual relations with a WOCBP, the male participant and his partner must use an acceptable, highly effective contraceptive method from screening until study completion, including the follow-up period, for at least 90 days after the last dose of study drug. Acceptable methods of contraception include the use of condoms and the use of an effective contraceptive for the female partner (WOCBP) that includes: OCPs, long-acting implantable hormones, injectable hormones, a vaginal ring, an IUD or having undergone tubal occlusion at least 6 weeks prior to screening. Participants who are abstinent from heterosexual intercourse as part of their usual lifestyle will also be eligible. 7. Male participants must agree to refrain from donating sperm through 90 days after 5 half-lives of the study product have elapsed from the last dose of study drug. 8. Ability and willingness to comply with all protocol procedures and restrictions (e.g., compliance with visit schedule, nebulization, dietary requirements, alcohol restrictions, etc.). 9. Ability to provide written informed consent.
Exclusion criteria
A participant who meets any of the following criteria must be excluded from the study: 1. History of any significant pulmonary disease including, but not limited to, asthma (including exercise induced asthma, allergy-induced asthma, or any history of asthma diagnosis including resolved childhood asthma), chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, and history of previous tuberculosis exposure with positive interferon gold test (without actual infection). Recent history of pneumonia or respiratory tract infection (within 6 weeks of screening). 2. History of clinically significant (as per Principal Investigator's discretion) upper respiratory disease including, but not limited to, nasal polyps or Samter's Triad. 3. Diagnosis of gastro-esophageal reflux disease (GERD). 4. History of cardiovascular disease including, but not limited to, heart failure (New York Heart Association (NYHA) class II, III or IV), myocardial infarction, angina, transient ischemic attack, cerebral infarct or haemorrhage, or history of an invasive cardiovascular therapeutic procedure such as coronary angioplasty, stent implantation, Coronary Artery Bypass Graft (CABG), etc. 5. Presence of a clinically significant electrocardiogram (ECG) finding at any time prior to initial IMP dose (e.g., QTcF greater than 450 msec for males, QTcF greater than 470 msec for females, left bundle branch block (LBBB), significant cardiac arrhythmia). 6. History of anaphylaxis, severe allergies or confirmed drug hypersensitivity reactions. 7. Known diagnosis of prolonged QT interval, history of arrhythmias (with the exception of sinus bradycardia) or previous episode of syncope thought to be of cardiac origin, or a family history of congenital long QT syndrome or unexplained death. 8. If female, positive pregnancy test at screening or on admission to the Unit on Day -1, or breastfeeding, or planning to breastfeed during the study. 9. Unwillingness to refrain from strenuous physical activity (e.g., heavy lifting, weight or fitness training) from 72 hours prior to admission and each other study day where safety laboratory samples are collected. 10. Unwillingness to refrain from sunbathing or use of a sunbed during the study. 11. Consumption of foods and/or drinks with known modulation of Cytochrome P450 Enzyme (CYP) activity (e.g., grapefruit / Seville oranges/pomelo, quinine containing products or drinks [tonic water/bitter lemon]) from 5 days before dosing until the final PK sample is collected. 12. The presence of clinically significant physical examination (including vital signs) or laboratory findings at screening or baseline that, in the opinion of the Principal Investigator, may interfere with any aspect of study conduct or interpretation of results or place a participant at heightened risk. 13. History of renal disease or abnormal kidney function tests at screening (glomerular filtration rate [GFR] less than 60 mL/min/1.73m2 as estimated using the CKD-EPI equation). 14. Participants with a history of, or active, clinically significant disease that could interfere with the interpretation of the study results or compromise the health of the volunteer. 15. Participants with a history of, or active, chronic liver disease due to alcohol, auto-immune mechanisms, primary biliary cholangitis, human immunodeficiency virus (HIV), hepatitis B virus (HBV), or active hepatitis C virus (HCV)-infection, Wilson's disease, alpha-1-antitrypsin deficiency, hemochromatosis, or metabolic dysfunction-associated steatohepatitis (MASH) disease. Participants with Gilbert’s disease and/or cholecystectomy will not be excluded. 16. Significant psychiatric history (including bipolar disorder, major depression, anxiety requiring behavioural or medical therapy, suicidal behaviour) in the opinion of the Principal Investigator within 2 years of screening. Approval of the Sponsor Medical Monitor should be sought for participants with a history of psychiatric disorders within 5 years prior to screening. 17. Abnormal laboratory results: a) amylase and/or lipase greater than the Upper Limit of Normal (ULN) (elevated values may be repeated once on a separate day). b) AST and/or ALT greater than ULN (elevated values less than 1.2 x ULN may be repeated once on a separate day). c) platelet count less than 150,000/mm^3 (decreased counts equal to or greater than 120,000/mm^3 may be repeated once on a separate day). d) Absolute eosinophil count greater than 1.5 x ULN (increased counts greater than 1.5 and less than 2.0 times the ULN may be repeated on a separate day). 18. Administration of vaccines/immunizations and/or boosters within 28 days prior to first dosing or if planned during the study. 19. Significant allergy to medical adhesive tape in the opinion of the Principal Investigator. 20. Use of any medications other than permitted contraceptives and hormone replacement therapy for post-menopausal women only (including prescription and non-prescription medications, and herbal supplements) within 14 days or 5 half-lives (whichever is longer) prior to admission to the Unit on Day -1, or an anticipated requirement for use of these during the study. Occasional use of paracetamol up to 4 g/day is permitted. Nutritional supplements may be permitted but must be discussed with the Sponsor Medical Monitor prior to participant enrolment. 21. History of, or suspected allergy or hypersensitivity to the investigational product components. 22. History of any active infection at the time of screening and/or within 28 days prior to first dosing. 24. Positive Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), Hepatitis C virus antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening. 25. Participation in any other clinical interventional study (including screening, dosing and follow-up) within 30 days or 5 half-lives prior to screening, whichever is longer. If clinical intervention was more than 6 months prior to screening and the participant is in follow-up only, eligibility may be assessed on a case-by-case basis in consultation with the Sponsor’s Medical Monitor. 26. Previous participation in a study with an investigational drug or device involving a biological targeted therapy, where final administration of the investigational drug or utilization of the device occurred within 24 weeks prior to first dosing. 27. Alcohol consumption greater than 14 units per week for men or greater than 7 units per week for women and/or positive alcohol breath test at screening and/or Day -1 (one unit is defined as 12 fluid ounces of regular beer (5 percent alcohol), 5 fluid ounces of wine (12 percent alcohol), or 1.5 fluid ounces of 80 proof (40 percent alcohol) distilled spirits). 28. Positive urine drug test at screening or on admission to the unit on Day -1. 29. Use of any tobacco and/or nicotine and/or inhaled marijuana product within 2 years prior to screening. 30. Use of non-nicotine-containing vaping product within 6 months prior to screening. 31. Existence of any surgical or medical condition that, in the judgement of the Principal Investigator, might interfere with the absorption, distribution, metabolism, or excretion of the investigational product. 32. Any anticipated upper respiratory, pulmonary, or abdominal procedures (e.g., surgery), that might interfere with the compliance or completion of the study. 33. Donation (or loss) of 470 mL or more whole blood during the 56 days prior to first dosing, or donation of plasma or platelets during the 14 days prior to first dosing, and/or plan to donate whole blood, plasma or platelets within 4 weeks after the last study-related blood draw.
Outcome results
None listed