None listed
Conditions
Brief summary
KER-047 is being developed by Keros Therapeutics Australia Pty Ltd as a potential treatment for Fibrodysplasia ossificans progressive (FOP). FOP is a rare genetic condition where the muscles, tendons and ligaments of the body slowly turn into bone. There are no approved treatments for FOP; This study aims to recruit healthy volunteers to determine the safety and pharmacokinetics of single and multiple dose of KER-047.
Interventions
Investigation product: KER-047 to be administered as an oral capsule or liquid with KER-047 dissolved in SyrSpend. Intervention adherence will be assessed by sponsor representative monitors. The monitors will asses compliance with the study protocol by performing an audit of nurses notes and pharmacy logs.
The study consists of two parts:
1. Single ascending dose (SAD) randomized 3 (study drug): 1 (placebo) in up to 10 cohorts.
Cohort 1: 1mg single oral dose administered on day 1
Cohort 2: 3mg s
Investigation product: KER-047 to be administered as an oral capsule or liquid with KER-047 dissolved in SyrSpend. Intervention adherence will be assessed by sponsor representative monitors. The monitors will asses compliance with the study protocol by performing an audit of nurses notes and pharmacy logs. The study consists of two parts: 1. Single ascending dose (SAD) randomized 3 (study drug): 1 (placebo) in up to 10 cohorts. Cohort 1: 1mg single oral dose administered on day 1 Cohort 2: 3mg single oral dose administered on day 1 Cohort 3: 10mg single oral dose administered on day 1 Cohort 4: 30mg single oral dose administered on day 1 Cohort 5: 100mg single oral dose administered on day 1 Cohort 6: 300mg single oral dose administered on day 1 Cohort 7: 30mg single oral dose administered on day 1 Cohort 8: 100mg single oral dose administered on day 1 Cohort 9: 300mg single oral dose administered on day 1 Cohort 10: 450mg single oral dose administered on day 1 2. Multiple ascending dose (MAD) The dose of the first MAD cohort will be determined by the Safety Review Committee (SRC), based on the PK and safety results of the SAD study. Dose increases for the MAD will be determined from the SAD. Up to 6 cohorts will be randomized 4 (study drug): 1 (placebo) with once daily, twice daily or every other day dosing for seven (7) or fourteen (14) days.
Sponsors
Keros Therapeutics, Australia Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Male Subjects: 1. 18 to 60 years old (MAD Cohorts 4, 5 & 6: 50 years) (inclusive) at screening; 2. Good health as determined by review of medical history, physical examination, vital signs, oxygen saturation, clinical laboratory tests, 12-lead ECG, and any abnormal findings are assessed as not clinically significant by the Investigator; 3. Non-smoker or social smokers who agrees to smoke less than or equal to 8 cigarettes per week or willing to abstain from smoking/nicotine products during the study; 4. Body weight between 50 and 110 kg inclusive and body mass index (BMI) between 18 and 32 kg/m2 (inclusive) at screening; Female Subjects: 1. Postmenopausal female aged 45 to 60 years (MAD Cohorts 4, 5 & 6: 50 years) (inclusive) at screening; 2. Good health as determined by review of medical history, physical examination, vital signs, oxygen saturation, clinical laboratory tests, 12-lead ECG, and any abnormal findings are assessed as not clinically significant by the Investigator; 3. Non-smoker or social smokers who agrees to smoke less than or equal to 8 cigarettes per week or willing to abstain from smoking/nicotine products during the study; 4. Body weight between 50 and 100 kg (inclusive) and BMI between 18.5 and 32 kg/m2 (inclusive) at screening.
Exclusion criteria
1. History of or current malignancy (excluding non-melanoma skin cancer that has been resected with no evidence of metastatic disease for 3 years); 2. Use of any prescription or over-the-counter medications taken within 7 days prior to dosing should be discussed with Investigator and Sponsor Medical Monitor (if deemed necessary). Use of medication should be ceased prior to dosing. Subject may be enrolled if the medication taken is not expected to interfere either with safety or study results; 3. Clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease; 4. Chronic stable diseases including migraines, hypertension, hyperthyroid disorder, hypothyroid disorder, gastroesophageal reflux disease, or mild depression/anxiety ; 5. History of opportunistic infection (e.g. invasive candidiasis or pneumocystis pneumonia); 6. Serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., septicemia) within the 3 months prior to screening; 7. History of severe allergic or anaphylactic reactions; 8. Surgery within the previous 3 months to screening (other than minor cosmetic surgery or minor dental procedures); 9. Fever (body temperature > 38°C) or symptomatic viral or bacterial infection within 2 weeks prior to screening that has not resolved prior to dosing; 10. Clinically relevant/significant laboratory findings (up to 2 repeats permitted) at screening including, but not limited to: • Alanine transaminase and Aspartate transaminase > 1.0 x upper limit of normal (ULN), isolated and mainly unconjugated hyperbilirubinemia consistent with Gilbert's should not be excluded; • Creatinine outside normal laboratory range; • Serum creatine kinase > 1.5 x ULN; 11. Treatment with another investigational drug, investigational device, or approved therapy for investigational use within 1 month or 7 half-lives prior to dosing.
Outcome results
None listed