A First-in-Human Study Evaluating AGA2118 in Postmenopausal Women
Study Details
Study Description
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 postmenopausal women and to assess the safety and tolerability of AGA2118 after multiple subcutaneous administrations in postmenopausal women with low bone mass.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Postmenopausal Women.
The study consists of the single ascending dose (SAD) part and the multiple ascending dose (MAD) part. In the SAD part, 56 healthy 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, 24 healthy postmenopausal women with low bone mass will be sequentially enrolled in various dose cohorts to receive multiple SC doses every 4 weeks of AGA2118 or placebo.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: AGA2118 In SAD part, various single doses of AGA2118 will be administered to the participants via either SC injection or IV infusion. The starting dose was 0.3 mg/kg, with sequential escalation up to 15 mg/kg. In MAD part, various multiple doses of AGA2118 will be administered every four weeks (Q4W) to the participants via SC injection for 12 weeks. The starting dose was 1 mg/kg, with sequential escalation up to 6 mg/kg. |
Drug: AGA2118
Part 1 - SAD study: SAD participants in various cohorts will receive various single dose of AGA2118 via either SC or IV.
Part 2 - MAD study: MAD participants in various cohorts will receive various multiple doses of AGA2118 Q4W via SC.
|
| Placebo Comparator: Placebo In SAD part, a single dose of placebo comparator will be used for each cohort of either SC or IV administration. In MAD part, multiple doses of placebo comparator will be used for each cohort of SC administration. |
Drug: Placebo
Part 1 - SAD study: SAD participants in various cohorts will receive a single dose of placebo via either SC or IV.
Part 2 - MAD study: MAD participants in various cohorts will receive multiple doses of placebo via SC.
|
Outcome Measures
Primary Outcome Measures
- Number of participants with treatment-emergent adverse events (TEAE) in Part 1 (SAD). [Up to 85 days]
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational product (IP), whether or not considered related to the IP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IP.
- Number of participants with clinically significant changes in total calcium (albumin-adjusted) in Part 1 (SAD). [Up to 85 days]
Serum calcium tested at Day 2, 8, 15, 29, 36, 57, 64, 85.
- Number of participants with clinically significant changes in blood pressure in Part 1 (SAD). [Up to 85 days]
Systolic and diastolic blood pressure measured (mmHg) at all clinic visits (Day 1, 2, 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85).
- Number of participants with clinically significant changes in heart rate in Part 1 (SAD). [Up to 85 days]
Heart rate measured by electrocardiogram (ECG) on Day 1, 2, 6, 11, 15, 22, 29, 43, 57, 71, 85.
- Number of participants with clinically significant changes in QTcF in Part 1 (SAD). [Up to 85 days]
QTcF (QT interval corrected for heart rate using Fridericia's formula) measured by electrocardiogram (ECG) on Day 1, 2, 6, 11, 15, 22, 29, 43, 57, 71, 85.
- Number of participants with treatment-emergent adverse events (TEAE) in Part 2 (MAD). [Up to 169 days]
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational product (IP), whether or not considered related to the IP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IP.
- Number of participants with clinically significant changes in total calcium (albumin-adjusted) in Part 2 (MAD). [Up to 169 days]
Serum calcium tested at Day 2, 8, 15, 29, 36, 57, 64, 85, 169.
- Number of participants with clinically significant changes in blood pressure in Part 2 (MAD). [Up to 169 days]
Systolic and diastolic blood pressure measured (mmHg) at all clinic visits (Day 1, 2, 4, 6, 8, 15, 22, 29, 36, 43, 57, 58, 60, 62, 64, 71, 78, 85, 99, 113, 127, 141, 155, 169).
- Number of participants with clinically significant changes in heart rate in Part 2 (MAD). [Up to day 169]
Heart rate measured by electrocardiogram (ECG) on Day 1, 2, 4, 15, 29, 36, 57, 64, 85, 169.
- Number of participants with clinically significant changes in QTcF in Part 2 (MAD). [Up to day 169]
QTcF (QT interval corrected for heart rate using Fridericia's formula) measured by electrocardiogram (ECG) on Day 1, 2, 4, 15, 29, 36, 57, 64, 85, 169.
Secondary Outcome Measures
- Maximum Concentration (Cmax) of AGA2118 [Part 1 (SAD): up to day 85; Part 2 (MAD) up to day 169]
Maximum concentration of AGA2118 after dosing.
- Time to maximum concentration (Tmax) of AGA2118 [Part 1 (SAD): up to day 85; Part 2 (MAD) up to day 169]
Time to maximum concentration of AGA2118 after dosing.
- Area under the concentration time curve (AUC) [Part 1 (SAD): up to day 85; Part 2 (MAD) up to day 169]
Definite integral of the curve describing the variation of AGA2118 in blood as a function of time.
- Terminal elimination half-life (t1/2) [Part 1 (SAD): up to day 85; Part 2 (MAD) up to day 169]
Time it takes for maximum concentration to half of maximum concentration of AGA2118.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Healthy postmenopausal women between 45 and 64 years of age for SAD; postmenopausal women between 45 to 80 years of age for MAD;
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BMI ≥ 18.5 and ≤ 35 kg/m^2 (for SAD and MAD).
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Generally healthy (as assessed by the investigator) but with low bone mass (for MAD only ).
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Nonsmokers, or light smokers, defined as ≤ 10 cigarettes/week (for SAD and MAD).
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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).
Exclusion Criteria:
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A bone fracture within 6 months (for SAD only).
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Previous exposure to AGA2118 (for MAD only).
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Any condition that would affect bone metabolism or has a history of low energy fractures as documented in medical history (for MAD only).
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Administration of the any medications that known to affect bone metabolism within 6 months of Day 1 unless otherwise specified (for SAD and MAD).
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Human immunodeficiency virus (HIV) infection (for SAD and MAD).
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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).
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Evidence of any of the following (for SAD and MAD):
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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
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current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range
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known intolerance to calcium supplements
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malignancy within the last 5 years, etc.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Q-Pharm Pty Ltd | Brisbane | Queensland | Australia | 4006 |
Sponsors and Collaborators
- Angitia Biopharmaceuticals
- Angitia Australia Pty Ltd
Investigators
- Study Director: Angitia Medical Director, Angitia Biopharmaceuticals Guangzhou Limited
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 21-001