None listed
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled, single-ascending dose (SAD, Part 1) and multiple-ascending dose study (MAD, Part 2) of KER-012 in healthy postmenopausal women. The study will evaluate the safety, tolerability and PK of KER-012. In addition, this study will explore the effects of KER-012 on muscle, bone, and adipose tissues, and determine the pharmacokinetic/pharmacodynamic (PD) relationship of those effects.
Interventions
KER-012 will be administered subcutaneously. Intervention adherence will be assessed by study monitors, this will be done by audit of nurses notes and pharmacy logs
The study consists of two parts:
Single Ascending Dose: 4 cohorts of 10 participants randomized 4 (study drug): 1 (placebo)
Cohort 1: 0.75 mg/kg single subcutaneous on day 1
Cohort 2: 1.5 mg/kg on single subcutaneous on day 1
Cohort 3: 3 mg/kg on single subcutaneous on day 1
Cohort 4: 5 mg/kg on single subcutaneous on day 1
Multip
KER-012 will be administered subcutaneously. Intervention adherence will be assessed by study monitors, this will be done by audit of nurses notes and pharmacy logs The study consists of two parts: Single Ascending Dose: 4 cohorts of 10 participants randomized 4 (study drug): 1 (placebo) Cohort 1: 0.75 mg/kg single subcutaneous on day 1 Cohort 2: 1.5 mg/kg on single subcutaneous on day 1 Cohort 3: 3 mg/kg on single subcutaneous on day 1 Cohort 4: 5 mg/kg on single subcutaneous on day 1 Multiple Ascending Dose: 3 cohorts of 8 participants randomized 3 (study drug): 1 (placebo) Cohort 1: 0.75 mg/kg subcutaneous on every 4 weeks (Q4W) on Days 1, 29, and 57 or dosing every 2 weeks (Q2W) on Days 1, 15, 29, 43, and 57 Cohort 2: 1.5 mg/kg subcutaneous on every 4 weeks (Q4W) on Days 1, 29, and 57 or dosing every 2 weeks (Q2W) on Days 1, 15, 29, 43, and 57 Cohort 3: 4.5 mg/kg subcutaneous on every 4 weeks (Q4W) on Days 1, 29, and 57 or dosing every 2 weeks (Q2W) on Days 1, 15, 29, 43, and 57
Sponsors
Keros Therapeutics, Inc.
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
45 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
For part 1 and part 2: 1. Postmenopausal female, aged 45 to 70 years (inclusive) at Screening. more than or equal to 6 months of spontaneous amenorrhea or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy. 2. Non-smoker or social smoker who agrees to smoke less than or equal to 8 cigarettes per week or is willing to abstain from smoking/nicotine products during the study including the follow-up period. 3. Body mass index of >18.5 kg/m2 to <32 kg/m2 at Screening. 4. In good health as determined by review of medical history, physical examination, vital signs, oxygen saturation, clinical laboratory tests, 12-lead electrocardiogram (ECG), and any abnormal findings that are assessed as not clinically significant by the Investigator.
Exclusion criteria
For part 1 and part 2: 1. Clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease. 2. History of or current malignancy (excluding basal cell carcinoma that has been resected with no evidence of metastatic disease for 3 years, or cervical intraepithelial neoplasia >5 years ago that was treated and not known to have recurred). 3. Current opportunistic infection (e.g., invasive candidiasis or pneumocystis pneumonia). 4. Serious local infections (e.g., cellulitis, abscess) or systemic infection (eg, septicemia) within the 3 months prior to Screening. 5. History of severe allergic or anaphylactic reaction(s) or hypersensitivity to recombinant proteins or excipients in the investigational drug 6. Surgery within 3 months prior to Screening (exception is various minor procedures [e.g., mole removal, minor cosmetic procedures, or minor dental procedures]). 7. Clinically relevant/significant laboratory findings at Screening (up to 1 repeat permitted) or on Day -1 (repeats not permitted) including, but not limited to: Alanine transaminase (ALT) and aspartate transaminase (AST) >1.2 × upper limit of normal (ULN); isolated and mainly unconjugated hyperbilirubinemia consistent with Gilbert's should not be excluded. 8. Fever (body temperature >38°C) or symptomatic viral or bacterial infection within 2 weeks prior to Screening that has not resolved prior to dosing. 9. Donated blood (1 unit or more) within 1 month prior to dosing or plans to donate blood during the study. 10. Hormone replacement therapy (i.e., estrogen, or estrogen plus progesterone) within 3 months prior to dosing or plans to begin hormone replacement therapy at any time during the study. Local estrogen therapy for vaginal atrophy replacement is permitted. 11. Systemic glucocorticoid therapy for more than 1 month within 6 months before Screening. 12. Changes in medications that may affect muscle function (e.g., high intensity statins, beta-blockers) within 3 months prior to dosing. Dose to remain stable while on study. 13. History of alcohol or drug abuse or drug addiction (including cannabis products) within the last 12 months prior to Screening. 14. Treatment with another investigational drug, investigational device, or approved therapy for investigational use within 1 month or 5 half-lives prior to dosing.
Outcome results
None listed