A First-in-Human Study Evaluating AGA2115 in Adult Healthy Volunteers and Adults and Adolescents With OI

Study Overview
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Brief Summary
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To understand if AGA2115 is safe and well tolerated in both healthy adults and adults/adolescents with Osteogenesis Imperfecta when given as a single dose or multiple doses.

Official Title
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A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AGA2115 in Adult Healthy Volunteers and in Adults and Adolescents (Aged 12 to 17 Inclusive) With Osteogenesis Imperfecta (OI)

Conditions
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Osteogenesis Imperfecta

Intervention / Treatment
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* Drug: AGA2115
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parts A and B: Healthy men and women ≥18 to ≤65 years old. Part C: Male and female adults ≥18 to ≤25 years old and adolescents ≥12 to ≤17 years old with a clinical diagnosis of OI Type I (mild) with a defect in COL1A1 and/or COL1A2, as confirmed by genetic testing. Vitamin D sufficiency (≥20 ng/mL (50 nmol/L) and agree to taking Calcium and Vitamin D supplements during the trial. Exclusion Criteria: Parts A and B: History of myocardial infarction or stroke (or other cardiovascular associated event deemed significant by investigator) within 12 months prior to Day 1. Malignancy within the last 5 years (basal cell carcinoma and squamous cell carcinoma that have been excised with no recurrence within the last 5 years is allowed). Hyper- or hypocalcemia. Known sensitivity to mammalian-derived drug preparations and/or any biologics. Pregnant or breastfeeding or planning to become pregnant (self or partner) at any time during the study. Part C: History of skeletal malignancies or bone metastases at any time. History of any skeletal instrumentation that would interfere with study imaging per investigator. Treatment with any bisphosphonates 3 months prior to screening and teriparatide, denosumab, setrusumab or other anabolic and anti-resorptive medications within 6 months prior to baseline. History of or concomitant uncontrolled diseases such as hypo-/hyperparathyroidism, hypo-/hyperthyroidism, Paget's disease, abnormal thyroid function or thyroid disease or other endocrine disorders or conditions that could affect bone metabolism. Hyper- or hypocalcemia. Known sensitivity to mammalian-derived drug preparations and/or any biologics. Pregnant or breastfeeding or planning to become pregnant (self or partner) at any time during the study. The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AGA2115<br>In Part A, up to 6 single ascending dose cohorts. In Part B, up to 3 multiple ascending dose cohorts. In Part C, up to 2 multiple dose cohorts. | Drug: AGA2115<br>* In Part A, participants will receive AGA2115 as a single dose administered as a subcutaneous (SC) injection (5 cohorts) or as an intravenous (IV) infusion (1 cohort). In Part B, participants will receive AGA2115 in multiple doses administered as a SC injection. In Part C, participants will receive AGA2115 in multiple doses administered as a SC injection.<br>|
| Placebo Comparator: Placebo<br>Participants will receive matching placebo. | Drug: Placebo<br>* In Part A, participants will receive single dose of placebo administered as a SC injection (5 cohorts) or IV infusion (1 cohort). In Part B, participants will receive multiple doses of placebo administered as a SC injection. In Part C, up to 2 cohorts will receive multiple doses of placebo administered as a SC injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-emergent adverse events (TEAEs) | Clinical significant changes in clinical laboratory tests, vital signs, and 12-lead electrocardiograms (ECGs) will be recorded as TEAEs. | Day 1 to up to end of study (approximately 85 days in Part A, approximately 169 days in Parts B and C) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed concentration (Cmax) of AGA2115 |  | Day 1 to up to end of study (approximately 85 days in Part A, approximately 169 days in Parts B and C) | 
| Time to maximum observed concentration (Tmax) of AGA2115 |  | Day 1 to up to end of study (approximately 85 days in Part A, approximately 169 days in Parts B and C) | 
| Area under the concentration time curve (AUC) of AGA2115 |  | Day 1 to up to end of study (approximately 85 days in Part A, approximately 169 days in Parts B and C) |