A Trial Evaluating Safety, Tolerability and Pharmacokinetics of Subcutaneous Single Doses of ACP-015 in Healthy Adult Male Subjects.

INTERVENTION: This is a single center, phase 1, entry into human, double‐blind, placebo‐controlled trial of TransCon CNP (ACP‐015) given subcutaneously (SC) to healthy adult male subjects. The trial comprises 6 dosing cohorts [up to 10 subjects per cohort (up to 8 active + 2 placebo)]. Study drug is administered SC in the abdomen in single doses to ascending dose cohorts (3 µg/kg, 10 µg/kg, 25 µg/kg, 75 µg/kg, 150 µg/kg, and 300 µg/kg CNP or until maximum tolerated dose (MTD) is identified. Each Single Ascending Dose (SAD) cohort consists of a screening visit (Day ‐28 to Day ‐2) to assess eligibility, a subsequent check‐in period in which screening is completed and eligibility is confirmed (Day ‐2 to Day ‐1), and a dosing period (Day 1) followed by a total safety observational period of 4 weeks after the SAD dose of study drug. Final eligibility for trial enrollment will be determined at check‐in to the clinic before randomization (Day ‐1) and dosing (on Day 1). Up to ten eligible subjects who have successfully completed screening will be enrolled into the lowest dose cohort that is yet to be filled, and randomly assigned (double‐blind) to receive TransCon CNP (ACP‐015) or matched placebo (4:1). Each SAD cohort will be enrolled and completed in a sequential fashion. There will be a sentinel pair of subjects (one receiving TransCon CNP (ACP‐015) and the other receiving placebo) for each of the six SAD cohorts who will be dosed first. After a period of approximately 72 hours, and at the discretion of the Principal Investigator, the same TransCon CNP (ACP‐015) or placebo dose will be given to the rest of the subjects in the respective SAD cohort. At the completion of the inpatient period after dosing for each cohort (inclusive of an inpatient period from Day ‐2 through Day 8), blinded clinical safety and laboratory parameters will be assessed in a Data and Safety Monitoring Board (DSMB) meeting to provide a recommendation on dose escalation either per protocol or with modifications. After receipt of the DSMB recommendation, the Safety Data Review Committee will make a decision either to continue with dose escalation or to pause (or stop) the dose escalation, after which subject dosing assignments will be unblinded. CONDITION: Achondrogenesis Achondroplasia Campomelic Dysplasia Hypochondroplasia Osteogenesis Imperfecta Skeletal Dysplasia in Children Thanatophoric Dysplasia PRIMARY OUTCOME: To determine the safety and tolerability of single ascending subcutaneous (SC) doses of ACP015 in healthy adult male subjects by observing the frequency of adverse events (AEs) reported after administration of ACP‐015. This is a composite outcome. ; ; Safety parameters as assessed by physical examination, vital signs, electrocardiography parameters including the QTc interval, clinical laboratory assessment (hematology, chemistry profiles, antibodies against CNP and mPEG, urinalysis), local tolerability assessment and adverse event data. ; ; Adverse event data will be collected from patient results, medical records and patient reporting. ; ; Local tolerability assessments to be completed will include, redness, bruising, swelling, and pain. Any local reaction evaluated as moderate or severe must be graded by a medical doctor. ; INCLUSION CRITERIA: ‐ Able to give Informed consent ‐ Able to comply with study protocol per investigator judgement ‐ Healthy adult males aged 25‐60 years at time of Screening ‐ Attainment of adult height (defined as subject’s confirmation of no change in standing height within 12 months of screening) ‐ BMI 18 – 27 kg/m2 ‐ Body weight <100 kg ‐ In good general health as determined by medical history, physical exams and laboratory evaluation at time of screening ; No identified or potential risks for use of ACP‐015 in humans has been established as no data is available in humans. However, risks include cardiovascular changes (decrease in blood pressure), and skeletal overgrowth and bone abnormalities (may affect musculoskeletal system and markers of bone turnover will be collected). SECONDARY OUTCOME: Changes in systemic biomarkers circulation, which may include, but are not limited to, BSAP, P1NP, CTx and NTproCNP. Changes in urine biomarkers circulation, which may include, but are not limited to, BSAP, P1NP, CTx and NTproCNP. To evaluate cGMP levels in systemic circulation after single ascending SC doses of TransCon CNP (ACP‐015) in healthy adult male subjects To evaluate cGMP levels in urine circulation after single ascending SC doses of TransCon CNP (ACP‐015) in healthy adult male subjects To evaluate the pharmacokinetic (PK) properties of single ascending SC doses of ACP‐015 in healthy adult male subjects ‐ Screening chemistry and hematology laboratory results in the normal range of the reference laboratory (or considered not clinically significant by the investigator) ‐ Subject must agree to not father a baby while on this study and for 90 days following the end of the study.. Males with female partners of child bearing potential must agree to use a barrier method of contraception (ie, condom) for the entire study period and for 90 days following the end of the study. Female partners must use a hi