Clinical trial NCT05225857: A First-in-Human Study Evaluating AGA2118 in Men and Postmenopausal Women
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Absolute Bioavailability, Pharmacokinetics, and Pharmacodynamics of AGA2118 in Men and Postmenopausal Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Osteoporosis
Lead sponsor: Angitia Biopharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Angitia Australia Pty Ltd
First posted: 2022-02-07
Enrollment: 90
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objectives of the study are to assess the safety and tolerability of AGA2118 after single subcutaneous or intravenous administration in healthy men and postmenopausal women and to assess the safety and tolerability of AGA2118 after multiple subcutaneous administrations in men and postmenopausal women.

Detailed description: This is a Phase I, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Absolute Bioavailability, Pharmacokinetics, and Pharmacodynamics of AGA2118 in Men and Postmenopausal Women.

The study consists of the single ascending dose (SAD) part and the multiple ascending dose (MAD) part. In the SAD part, up to 56 healthy men and postmenopausal women will be sequentially enrolled to receive a single subcutaneous (SC) dose of AGA2118 or a single intravenous (IV) dose of AGA2118 or placebo. In the MAD part, up to 32 healthy men and postmenopausal women will be sequentially enrolled in various dose cohorts to receive multiple SC doses every 4 weeks of AGA2118 or placebo.

Eligibility criteria: Inclusion Criteria:

1. Healthy men ≥ 30 and ≤ 65 years of age or postmenopausal women ≥ 45 and ≤ 65 years of age for SAD and MAD;
2. BMI ≥ 18.5 and ≤ 32 kg/m\^2 (for SAD and MAD).
3. Generally healthy (as assessed by the investigator).
4. Nonsmokers, or light smokers, defined as ≤ 3 cigarettes/day (or equivalent) (for SAD and MAD).
5. Able and willing to correctly and independently complete all study procedures and able to read, understand, and provide written informed consent after the nature of the study has been fully explained and must be willing to comply with all study requirements and procedures (for SAD and MAD).
6. A male who is sterile or agrees to the following during the Treatment Period and for at least 6 months after the final dose of investigational product

   * Refrain from donating fresh unwashed semen

Plus, either

* Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent

OR

* Must agree to use contraception as detailed below

  * Agree to use a male condom plus a female partner to use a highly effective method of contraception with a woman of childbearing potential who is not currently pregnant
  * Agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person

Exclusion Criteria:

1. A bone fracture within 6 months (for SAD only).
2. Previous exposure to AGA2118 (for MAD only).
3. Any condition that would affect bone metabolism or has a history of low energy fractures as documented in medical history (for MAD only).
4. Administration of the any medications that known to affect bone metabolism within 6 months of Day 1 unless otherwise specified (for SAD and MAD).
5. Human immunodeficiency virus (HIV) infection (for SAD and MAD).
6. Active chronic hepatitis B (HBV) or hepatitis C (HCV) infection including hepatitis B surface antigen and hepatitis C antigen positive participants with or without abnormal liver enzymes (for SAD and MAD).
7. Evidence of any of the following (for SAD and MAD):

   1. creatinine ≥ 1.5 × ULN, or estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m\^2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula at screening
   2. current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range
   3. known intolerance to calcium supplements
   4. malignancy within the last 5 years, etc.

Primary outcomes:
measure: Number of participants with treatment-emergent adverse events (TEAE) in Part 1 (SAD).
timeFrame: Up to 85 days
measure: Number of participants with clinically significant changes in total calcium (albumin-adjusted) in Part 1 (SAD).
timeFrame: Up to 85 days
measure: Number of participants with clinically significant changes in blood pressure in Part 1 (SAD).
timeFrame: Up to 85 days
measure: Number of participants with clinically significant changes in heart rate in Part 1 (SAD).
timeFrame: Up to 85 days
measure: Number of participants with clinically significant changes in QTcF in Part 1 (SAD).
timeFrame: Up to 85 days
measure: Number of participants with treatment-emergent adverse events (TEAE) in Part 2 (MAD).
timeFrame: Up to 169 days
measure: Number of participants with clinically significant changes in total calcium (albumin-adjusted) in Part 2 (MAD).
timeFrame: Up to 169 days
measure: Number of participants with clinically significant changes in blood pressure in Part 2 (MAD).
timeFrame: Up to 169 days
measure: Number of participants with clinically significant changes in heart rate in Part 2 (MAD).
timeFrame: Up to day 169
measure: Number of participants with clinically significant changes in QTcF in Part 2 (MAD).
timeFrame: Up to day 169
Secondary outcomes:
measure: Maximum Concentration (Cmax) of AGA2118
timeFrame: Part 1 (SAD): up to day 85; Part 2 (MAD) up to day 169
measure: Time to maximum concentration (Tmax) of AGA2118
timeFrame: Part 1 (SAD): up to day 85; Part 2 (MAD) up to day 169
measure: Area under the concentration time curve (AUC)
timeFrame: Part 1 (SAD): up to day 85; Part 2 (MAD) up to day 169
measure: Terminal elimination half-life (t1/2)
timeFrame: Part 1 (SAD): up to day 85; Part 2 (MAD) up to day 169
Other outcomes:
Locations:
city: Brisbane
country: Australia
facility: Q-Pharm Pty Ltd
state: Queensland
city: Melbourne
country: Australia
facility: Nucleus Network Pty Ltd.
state: Victoria
Study officials:
affiliation: Angitia Incorporated Limited
name: Angitia Medical Director
role: STUDY_DIRECTOR
References: