None listed
Conditions
Brief summary
This research project is testing the safety, tolerability, immunology (how the study drug affects the immune system), pharmacokinetics (how the body effects the study drug) and pharmacodynamics (how the study drug effects the body) of single and multiple doses of a new drug called ACP-014 when given as a subcutaneous (into the skin) injection. Ascendis Pharma is developing the drug ACP-014 for the potential his study will run in 3 Parts: • Single Ascending Dose (SAD) Phase: will assess the effect of a single ascending dose of ACP-014 or placebo when administered as a subcutaneous (under the skin) injection abdomen. • Cross Over (Cohort X) Phase: will assess the effect of a single subcutaneous dose of ACP-014 in their abdomen and thigh. This phase of the study involves all participants receiving both study treatments in a particular sequence. • Multiple Ascending Dose (MAD) Phase: will assess the effect of multiple ascending daily doses of ACP-014 when administered as subcutaneous injections into the abdomen. Up to 80 participants will be enrolled in up to 8 cohorts (groups) with up to 10 participants in each cohort. In each cohort, 8 participants will receive the active drug (ACP-014) and 2 will receive the placebo. This study is a dose escalation study and total participation consists of 35 days.
Interventions
Participants will be enrolled to 1 of the following 3 interventions:
In Part 1 of the trial, comprising up to 8 single ascending dose (SAD) cohorts of 10 subjects each, study drug is administered SC in the abdomen in single doses to ascending dose cohorts [3.5µg, 12 µg, 32 µg, 48 µg, 72 µg, 100 µg, 124 µg, and 152 µg ACP-014 (N=8) or placebo (N=2)] until dose limiting toxicity (DLT) is observed.
Cohort X- After completion of the SAD cohorts, up to 16 subjects will be enrolled in the subsequen
Participants will be enrolled to 1 of the following 3 interventions: In Part 1 of the trial, comprising up to 8 single ascending dose (SAD) cohorts of 10 subjects each, study drug is administered SC in the abdomen in single doses to ascending dose cohorts [3.5µg, 12 µg, 32 µg, 48 µg, 72 µg, 100 µg, 124 µg, and 152 µg ACP-014 (N=8) or placebo (N=2)] until dose limiting toxicity (DLT) is observed. Cohort X- After completion of the SAD cohorts, up to 16 subjects will be enrolled in the subsequent 2 by 2 randomized crossover cohort. 8 subjects (optimally 4 males and 4 females) will receive single SC doses of 12 µgACP-014 in either the abdomen/thigh (A/T) or the thigh/abdomen (T/A) in a crossover fashion. The other 8 subjects (optimally 4 males and 4 females) will receive the highest tolerated single dose of ACP-014 in either A/T or T/A in a crossover fashion to obtain initial information on potential PK differences between SC dosing in the abdomen vs. the thigh. All subjects will receive two single doses of ACP-014 at least 7 days apart. In Part 2, study drug is administered SC in the abdomen daily for 10 days to approximate steady-state to up to 9 multiple ascending dose (MAD) cohorts of 10 subjects each (8 subjects receiving ACP-014 , and 2 subjects receiving placebo). The initial dose cohort of 3.5 µg ACP-014 daily may begin after completion of the 32 µg SAD cohort, based on an expected accumulation ratio of 3 plus an additional 10-fold safety margin. The 2nd MAD dose will be 7.0 µg/day, followed by 12 µg/day, 16 µg/day, 20 µg/day, 24 µg/day, 32 µg/day, 40µg/day and potentially 48 µg/day.
Sponsors
Ascendis Pharma Bone Diseases A/S
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1) Healthy adult males and females aged 18-60 years 2) Body mass index (BMI) 18.5 – 27 kg/m2 3) Able to provide informed consent 4) All male and females of childbearing potential must agree to use a barrier method of contraception from the time of signing informed consent until 30 days after study completion if engaging in sexual activity, unless a female of childbearing potential has been using a non-barrier highly effective forms of contraception including oral contraceptive pills, long-acting implantable hormones, injectable hormones, a vaginal ring or an intrauterine device and agrees to continue this form of contraception until 30 days after study completion, or has had a tubal ligation, or their male partner has had a vasectomy. Subjects with same sex partners (abstinence from penile-vaginal intercourse) are eligible when this is their preferred and usual lifestyle. Male subjects must use contraception (ie, male condom) or practice complete abstinence for 30 days after study completion and must not donate sperm during this time. 5) Any subjects using calcium/minerals and/or vitamin D supplements at screening must continue the same doses of these supplements throughout the study.
Exclusion criteria
1) History or presence of malignant disease, other than basal cell epithelioma/carcinoma or completely resected squamous skin cancer with no recurrence for 12 months 2) Any history of hyperparathyroidism, hypoparathyroidism, hypercalcemia, hypercalciuria, kidney stones, Familial Benign Hypocalciuric Hypercalcemia, osteomalacia, Paget’s disease, osteoporosis, or any type of metabolic bone disease or radiation therapy to the skeleton 3) Pregnant or lactating females 4) History of diabetes mellitus 5) Use of any prescription drug other than hormonal contraception [(oral contraceptives pills (OCP’s), longacting implantable hormones, injectable hormones, a vaginal ring or an intrauterine device (IUD)] within 7 days prior admission without approval of the medical monitor/expert 6) Screening level 25-hydroxyvitamin D3 of < 25 ng/mL 7) History of drug abuse 8) Known or suspected HIV-positive status 9) Known or suspected infection with hepatitis B or C 10) Known hypersensitivity to the components of the trial medication 11) The subject is likely to be non-compliant with respect to trial conduct 12) Participation in any other trial of an investigational agent within 30 days prior to entry 13) Any other reason that in the opinion of the investigator would prevent the subject from completing participation or following the trial schedule.
Outcome results
None listed