A First-in-Human Study Evaluating AGA2118 in Men and Postmenopausal Women

NCT05225857 | Completed Phase 1

• 1 other identifier: 21-001
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

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.

Conditions

Osteoporosis

Outcome Measures

Primary Outcomes (10)

• Number of participants with treatment-emergent adverse events (TEAE) in Part 1 (SAD).

  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.

  Up to 85 days

• Number of participants with clinically significant changes in total calcium (albumin-adjusted) in Part 1 (SAD).

  Serum calcium tested at Day 2, 4, 6, 15, 29, 85.

  Up to 85 days

• Number of participants with clinically significant changes in blood pressure in Part 1 (SAD).

  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).

  Up to 85 days

• Number of participants with clinically significant changes in heart rate in Part 1 (SAD).

  Heart rate measured by electrocardiogram (ECG) on Day 1, 2, 4, 6, 15, 29, 85.

  Up to 85 days

• Number of participants with clinically significant changes in QTcF in Part 1 (SAD).

  QTcF (QT interval corrected for heart rate using Fridericia's formula) measured by electrocardiogram (ECG) on Day 1, 2, 4, 6, 15, 29, 43, 57, 71, 85.

  Up to 85 days

• Number of participants with treatment-emergent adverse events (TEAE) in Part 2 (MAD).

  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.

  Up to 169 days

• Number of participants with clinically significant changes in total calcium (albumin-adjusted) in Part 2 (MAD).

  Serum calcium tested at Day 2, 8, 15, 29, 36, 57, 64, 85, 169.

  Up to 169 days

• Number of participants with clinically significant changes in blood pressure in Part 2 (MAD).

  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).

  Up to 169 days

• Number of participants with clinically significant changes in heart rate in Part 2 (MAD).

  Heart rate measured by electrocardiogram (ECG) on Day 1, 2, 4, 15, 29, 36, 57, 64, 85, 169.

  Up to day 169

• Number of participants with clinically significant changes in QTcF in Part 2 (MAD).

  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.

  Up to day 169

Secondary Outcomes (4)

• Maximum Concentration (Cmax) of AGA2118

  Part 1 (SAD): up to day 85; Part 2 (MAD) up to day 169

• Time to maximum concentration (Tmax) of AGA2118

  Part 1 (SAD): up to day 85; Part 2 (MAD) up to day 169

• Area under the concentration time curve (AUC)

  Part 1 (SAD): up to day 85; Part 2 (MAD) up to day 169

• Terminal elimination half-life (t1/2)

  Part 1 (SAD): up to day 85; Part 2 (MAD) up to day 169

Study Arms (2)

AGA2118

EXPERIMENTAL

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 12 mg/kg.

Drug: AGA2118

Placebo

PLACEBO COMPARATOR

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

Interventions

AGA2118 DRUG

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.

AGA2118

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy men ≥ 30 and ≤ 65 years of age or postmenopausal women ≥ 45 and ≤ 65 years of age for SAD and MAD;
• BMI ≥ 18.5 and ≤ 32 kg/m\^2 (for SAD and MAD).
• Generally healthy (as assessed by the investigator).
• Nonsmokers, or light smokers, defined as ≤ 3 cigarettes/day (or equivalent) (for SAD and MAD).
• 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).
• 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
• 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

You may not qualify if:

• A bone fracture within 6 months (for SAD only).
• Previous exposure to AGA2118 (for MAD only).
• Any condition that would affect bone metabolism or has a history of low energy fractures as documented in medical history (for MAD only).
• Administration of the any medications that known to affect bone metabolism within 6 months of Day 1 unless otherwise specified (for SAD and MAD).
• Human immunodeficiency virus (HIV) infection (for SAD and MAD).
• 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).
• Evidence of any of the following (for SAD and MAD):
• 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
• current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range
• known intolerance to calcium supplements
• malignancy within the last 5 years, etc.

Sponsors & Collaborators

• Angitia Biopharmaceuticals: lead
• Angitia Australia Pty Ltd: collaborator

Study Sites (2)

Q-Pharm Pty Ltd

Brisbane, Queensland, 4006, Australia

Location

Nucleus Network Pty Ltd.

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Conditions

Osteoporosis

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Angitia Medical Director

  Angitia Incorporated Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2022
• First Posted: February 7, 2022
• Study Start: June 28, 2022
• Primary Completion: January 13, 2024
• Study Completion: January 13, 2024
• Last Updated: February 5, 2024

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2)