Comparative Study of Efficacy, Pharmacokinetics, and Safety of Denosumab (MAB-22) Versus EU-Sourced Denosumab in Postmenopausal Osteoporosis
- Trial ID
- 2024-512417-41-00
- Protocol
- MAB-22-301
- Sponsor
- Xentria Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare **MAB-22** and Prolia® (EU-authorized) in postmenopausal women with **osteoporosis** to demonstrate biosimilarity. This will be assessed by evaluating the efficacy profile in terms of bone mineral density (BMD) and the pharmacodynamic (PD) profile in terms of serum cross-linked C telopeptide of type I collagen (sCTX). The clinical relevance of this objective lies in establishing the therapeutic equivalence of MAB-22 to an established treatment, Prolia®, which is crucial for providing alternative treatment options for osteoporosis.
Secondary objectives include: - Assessing the efficacy, pharmacodynamics (PD), and pharmacokinetics (PK) of MAB-22 versus Prolia® in postmenopausal women with osteoporosis. - Evaluating the safety, tolerability, and immunogenicity of MAB-22 compared to Prolia®. - Assessing the efficacy, PD, and PK of MAB-22 versus Prolia® and the switch from Prolia® to MAB-22 during Treatment Period 2 (TP2). - Evaluating the safety and immunogenicity of MAB-22 versus Prolia® and the switch from Prolia® to MAB-22 during TP2.
Participants
The clinical trial involves a study population of **postmenopausal women** diagnosed with **osteoporosis**, specifically targeting those between the ages of 55 and 80. The trial does not include male participants or vulnerable populations. Participants were selected based on specific health criteria, including a body weight between 50 kg and 90 kg, and adequate organ function as defined by standard laboratory measures. The study focuses on individuals with a bone mineral density T-score between -2.5 and -4.0, as measured by DXA, and requires that at least three vertebrae in the L1-L4 region and at least one hip joint are evaluable. The sponsor has not provided the total number of participants involved in the trial. Lifestyle factors such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is designed as a **randomized, double-blind, parallel-group, active-controlled** study to evaluate the efficacy, pharmacokinetics, pharmacodynamics, safety, and immunogenicity of MAB-22 compared to Prolia® in postmenopausal women with **osteoporosis**. The trial aims to demonstrate biosimilarity between the two treatments, focusing on the efficacy profile in terms of bone mineral density (BMD) and the pharmacodynamic profile concerning serum cross-linked C telopeptide of type I collagen (sCTX). The study is expected to last until October 2026, with recruitment starting in October 2024.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as postmenopausal status, age, body weight, and adequate organ function. The primary efficacy endpoint is the percentage change from baseline in lumbar spine BMD at Week 52, while the primary pharmacodynamic endpoint is the area under the effect curve of sCTX over the initial 6-month period. Secondary endpoints include changes in BMD at various sites and time points, pharmacokinetic parameters, safety assessments, and immunogenicity evaluations.
The trial will involve multiple follow-up visits, including assessments at Weeks 26, 52, and 78, to monitor the participants' response to treatment and collect data on secondary endpoints. The end-of-study visit will conclude the trial, ensuring all necessary data is collected and participants' health is evaluated. The expected length of participant involvement is approximately two years, with conditions for early termination including withdrawal of consent, adverse events, or non-compliance with the study protocol.
Treatment
The clinical trial involves the administration of **MAB-22**, an experimental medication formulated as a **solution for injection**. The active substance in MAB-22 is **denosumab**, a protein-based therapeutic agent. MAB-22 is provided in a prefilled syringe and is administered via **subcutaneous injection**. The dosage is set at 60 mg per milliliter, with a maximum daily and total dose of 60 mg. The treatment period is limited to one month. The administration of MAB-22 is monitored to ensure compliance with the dosing schedule.
The comparator treatment in this study is **Prolia**, a commercially available medication also containing **denosumab** as its active ingredient. Prolia is provided as a **solution for injection in a pre-filled syringe** and is administered through **subcutaneous injection**. The dosage for Prolia is similarly set at 60 mg per milliliter, with a maximum daily and total dose of 60 mg, and the treatment period is also one month. Prolia is sourced from the European Union and is used to establish a reference for comparing the efficacy, pharmacokinetics, pharmacodynamics, safety, and immunogenicity of MAB-22.
Both MAB-22 and Prolia are administered using prefilled syringes, which do not possess a CE mark. The trial ensures that participants adhere to the dosing schedule through regular monitoring. The study aims to demonstrate the biosimilarity of MAB-22 to Prolia in postmenopausal women with osteoporosis, focusing on bone mineral density and serum cross-linked C telopeptide of type I collagen as primary endpoints.
Efficacy
The efficacy of the clinical trial comparing MAB-22 and Prolia® in postmenopausal women with osteoporosis will be assessed using specific endpoints. The primary efficacy endpoint is the percentage change from baseline in lumbar spine bone mineral density (LS BMD) at Week 52. Additionally, the pharmacodynamic (PD) coprimary endpoint involves the area under the effect curve (AUEC) of serum cross-linked C telopeptide of type I collagen (sCTX) over the initial 6-month period, from Day 1 to Week 26 (predose).
Secondary efficacy endpoints include the percentage change from baseline in LS BMD at Weeks 26 and 78, as well as changes in total hip BMD (TH-BMD) and femoral neck BMD (FM-BMD) at Weeks 26, 52, and 78. Secondary PD endpoints will evaluate the percentage change from baseline in sCTX and procollagen type 1 N-terminal propeptide (P1NP) at Weeks 26 and 52, the maximum percentage change from baseline in sCTX at Week 26, and the AUEC of P1NP over the initial 6-month period.
Data collection will occur at specified timepoints, including Weeks 26, 52, and 78, using validated methods such as dual-energy X-ray absorptiometry (DXA) for BMD measurements. The analysis will focus on comparing the efficacy profiles of MAB-22 and Prolia® to demonstrate biosimilarity in terms of bone mineral density and pharmacodynamic responses.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Individuals must meet all of the following inclusion criteria to be included in the study: Signed informed consent must be obtained before participation in the study.
- Postmenopausal women diagnosed with osteoporosis (consistent with a LS BMD [L1-L4] or TH-BMD T-score of ≤ -2.5 and ≥ -4.0 as measured by DXA at screening). Postmenopausal status is defined as at least 12 consecutive months of amenorrhea before date of screening, for which there is no other obvious pathological or physiological cause.
- Between ≥55 and ≤80 years of age at screening.
- Body weight ≥50 kg and ≤90 kg at screening.
- At least 3 vertebrae in the L1-L4 region (vertebrae to be assessed by local reading of lateral spine x-ray at screening) and at least one hip joint are evaluable by DXA.
- Adequate organ function as defined by the following criteria: a. Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN). b. Total serum bilirubin ≤1.5 × ULN. c. Absolute neutrophil count ≥1500 cells/µL (SI units: ≥1.5 × 109/L). d. Platelet count ≥100,000 cells/µL (SI units: ≥100 × 109/L) and ≤ULN. e. Hemoglobin ≥11 g/dL and ≤ULN. f. Albumin-adjusted serum calcium within the normal range for the testing laboratory. g. Estimated glomerular filtration rate >45 mL/min.
Exclusion Criteria
- Individuals meeting any of the following exclusion criteria are ineligible to participate in this study: Previous exposure to denosumab (Prolia®, Xgeva®, or biosimilar denosumab).
- History of hypersensitivity to any recombinant protein drugs or any of the excipients used in MAB-22 or Prolia®.
- History and/or presence of 1 severe or more than 2 moderate vertebral fractures or hip fractures (as determined by local reading of lateral spine x-ray at screening). Osteoporotic-related fracture (i.e., crush or wedge vertebral fracture or hip fracture) known or suspected to have occurred within 6 months of randomization.
- Recent long bone fracture (within 6 months) before screening. Presence of active healing fracture according to assessment of investigators.
- History and/or presence of bone metastases, bone disease, or metabolic disease, other than osteoporosis, which could interfere with the interpretation of the findings (e.g., osteogenesis imperfecta, osteopetrosis, osteomalacia, rheumatoid arthritis, Paget’s disease, ankylosing spondylitis, Cushing’s disease, hyperprolactinemia, malabsorption syndrome, hypoparathyroidism or hyperparathyroidism [irrespective of current controlled or uncontrolled status], hypocalcemia or hypercalcemia [based on albumin-adjusted serum calcium]).
- Malignancy within the 5 years before screening (except cervical carcinoma in situ or basal cell carcinoma, which are acceptable).
- Ongoing use of any osteoporosis treatment (other than calcium and vitamin D supplements).
- Other bone active drugs including heparin, anti-convulsives (with the exception of benzodiazepines), systemic ketoconazole, adrenocorticotropic hormone, lithium, gonadotropin releasing hormone agonists, and anabolic steroids, within the past 3 months before the first administration of study treatment.
- Systemic glucocorticosteroids (≥5 mg prednisone equivalent per day for ≥10 days or a total cumulative dose of ≥50 mg) within the past 3 months before screening.
- Use of other investigational drugs within 2 months of screening (or 5 half-lives of the drug or until the expected PD effect of the drug has returned to baseline, whichever is longer) or longer if required by local regulations.
- Oral or dental conditions: osteomyelitis or history and/or presence of osteonecrosis of the jaw (ONJ), presence of risk factors for ONJ (e.g., periodontal disease, poorly fitting dentures, invasive dental procedures such as tooth extractions in 6 months before screening), active dental or jaw condition which requires oral surgery and/or planned invasive dental procedure.
- Recent tooth extraction (within 6 months of the screening visit). Edentulous participants are permitted to enroll in the study, as long as the most recent tooth extraction occurred >6 months of the screening visit.
- Vitamin D deficiency (25-[OH] vitamin D serum level <20 ng/mL). Vitamin D repletion is permitted at the discretion of the investigator, and participants will be rescreened to reevaluate vitamin D level post-repletion.
- Known intolerance to, or malabsorption of calcium or vitamin D supplements.
- History and/or presence of a severe allergic reaction (e.g., anaphylaxis).
- Has a hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) antibody positive at screening.
- History and/or presence of significant cardiac disease as per investigator’s discretion, including but not restricted to: ECG abnormalities at screening indicating significant risk of safety for participants participating in the study, history and/or presence of myocardial infarction within 6 months before screening, history and/or presence of New York Heart Association (NYHA) class III or IV heart failure.
- History of prior allogeneic transplantation.
- Have a history of alcohol or drug abuse in the judgment of the investigator within the previous 12 months before screening.
- Unstable systemic disease including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, or myocardial infarction within 6 months before randomization.
- Have major surgery (including surgery to bone), or significant traumatic injury occurring within 4 weeks before randomization.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Not Recruiting | 28 Oct 2024 | 80 |
 Czechia | Not Recruiting | 28 Oct 2024 | 35 |
 Poland | Not Recruiting | 28 Oct 2024 | 325 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
MAB-22 | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS | 60.00 | 1 | PRD11152764 |
Prolia 60 mg solution for injection in pre-filled syringe | Comparator | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS INJECTION | 60.00 | 1 | PRD3618671 |
Prolia 60 mg solution for injection in pre-filled syringe | Comparator | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS INJECTION | 60.00 | 1 | PRD385447 |
Prolia 60 mg solution for injection in pre-filled syringe | Comparator | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS INJECTION | 60.00 | 1 | PRD3618881 |