Phase 2 Randomized, Double‑Blind, Placebo‑Controlled Study of AGA2115, a Humanised IgG4 Bispecific Anti‑Sclerostin/DKK1 Antibody, in Adults with Osteogenesis Imperfecta

The primary objective is to evaluate the effect of AGA2115 on bone mineral density (BMD) at the lumbar spine after 12 months of treatment in adults with type I, III, or IV osteogenesis imperfecta, thereby assessing its potential to enhance skeletal strength and reduce fracture risk in this population.

68 participants were enrolled, comprising both male and female adults aged 18 to 75 years. All subjects had a confirmed diagnosis of Osteogenesis Imperfecta (type I, III, or IV) with documented pathogenic variants in the COL1A1 or COL1A2 genes. Eligibility required a lumbar spine, total hip, or femoral neck bone mineral density T‑score of ≤ ‑1.0 and the ability to provide signed informed consent. The cohort was selected based on clinical diagnosis corroborated by genetic testing and met the predefined inclusion criteria; individuals not meeting these criteria were excluded. The population was otherwise generally healthy aside from the underlying bone disorder.

The trial is a Phase 2, multi‑center, randomized, double‑blind, placebo‑controlled, dose‑ranging study evaluating subcutaneous AGA2115 (2000 mg) versus matching placebo in adults with genetically confirmed Type I, III, or IV osteogenesis imperfecta. Eligible participants (18–75 years, lumbar spine or hip T‑score ≤ ‑1.0) undergo a screening visit to confirm eligibility, followed by baseline assessments and the first study injection. Subsequent visits occur at regular intervals (e.g., months 1, 3, 6, 9) to monitor safety, collect pharmacodynamic data, and administer additional doses as per the dosing schedule. The primary efficacy endpoint, percent change from baseline in lumbar spine BMD at month 12, is measured at the 12‑month visit, which also serves as the end‑of‑study assessment; participants remain in the trial for approximately 12 months after randomization. Early termination may occur if a participant experiences a serious adverse event, withdraws consent, or fails to meet protocol compliance criteria.

The investigational product, AGA2115, is a humanised IgG4 bispecific monoclonal antibody directed against sclerostin and Dickkopf‑related protein 1, supplied as a 2000 mg solution for injection. It is administered by subcutaneous injection in a volume appropriate for the dose and is given according to the study’s predefined dosing schedule, with each administration occurring at designated study visits. Dosing compliance is monitored through documented site‑recorded administration logs and verification of returned vials.

The control arm receives a matching Placebo formulation, presented as a solution for injection identical in appearance to the active product. It is delivered by subcutaneous injection on the same schedule as the investigational product to maintain blinding, with compliance similarly tracked via administration records and accountability checks.

The primary efficacy parameter is the percent change from baseline at month 12 in lumbar spine BMD. This endpoint will be evaluated by comparing BMD values obtained at the start of the study with those measured at the 12‑month visit.

Bone mineral density measurements will be collected using a validated densitometry technique at baseline and at month 12. The change will be expressed as a percentage of the baseline value and analyzed according to the predefined statistical analysis plan.