A Randomized, Double-blind, Parallel-group, Active-controlled Study to Compare the Efficacy, Pharmacokinetics, Pharmacodynamics, Safety, and Immunogenicity of MAB-22 Versus Prolia® Sourced from the European Union in Postmenopausal Women with Osteoporosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Xentria Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

completed 11 Nov 2025

Decision date (initial)

2024-09-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Xentria Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Pharmacodynamic, Others, Safety

To compare MAB-22 and Prolia® (EU-authorized) in postmenopausal women with osteoporosis to demonstrate biosimilarity with respect to the following:
- Efficacy profile in terms of bone mineral density (BMD).
- Pharmacodynamic (PD) profile in terms of serum cross-linked C telopeptide of type I collagen (sCTX).

Secondary objectives 4

1. To assess the efficacy, PD, and pharmacokinetics (PK) of MAB-22 versus Prolia® (EU-authorized) in postmenopausal women with osteoporosis.
2. To assess the safety, tolerability, and immunogenicity of MAB-22 versus Prolia® (EU-authorized) in postmenopausal women with osteoporosis.
3. To assess the efficacy, PD, and PK of MAB-22 versus Prolia® (EU-authorized) and Prolia® switch to MAB-22 during Treatment Period 2 (TP2).
4. To assess the safety and immunogenicity of MAB-22 versus Prolia® (EU-authorized) and Prolia® switch to MAB-22 during TP2.

Conditions and MedDRA coding

Osteoporosis

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 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.
2. 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.
3. Between ≥55 and ≤80 years of age at screening.
4. Body weight ≥50 kg and ≤90 kg at screening.
5. 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.
6. 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 21

1. Individuals meeting any of the following exclusion criteria are ineligible to participate in this study: Previous exposure to denosumab (Prolia®, Xgeva®, or biosimilar denosumab).
2. History of hypersensitivity to any recombinant protein drugs or any of the excipients used in MAB-22 or Prolia®.
3. 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.
4. Recent long bone fracture (within 6 months) before screening. Presence of active healing fracture according to assessment of investigators.
5. 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]).
6. Malignancy within the 5 years before screening (except cervical carcinoma in situ or basal cell carcinoma, which are acceptable).
7. Ongoing use of any osteoporosis treatment (other than calcium and vitamin D supplements).
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. Known intolerance to, or malabsorption of calcium or vitamin D supplements.
15. History and/or presence of a severe allergic reaction (e.g., anaphylaxis).
16. Has a hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) antibody positive at screening.
17. 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.
18. History of prior allogeneic transplantation.
19. Have a history of alcohol or drug abuse in the judgment of the investigator within the previous 12 months before screening.
20. Unstable systemic disease including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, or myocardial infarction within 6 months before randomization.
21. Have major surgery (including surgery to bone), or significant traumatic injury occurring within 4 weeks before randomization.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Efficacy coprimary endpoint: percentage change from baseline (%CfB) in lumbar spine BMD (LS BMD) at Week 52.
2. PD coprimary endpoint: area under the effect curve (AUEC) of sCTX over the initial 6 month period (Day 1 to Week 26 [predose]).

Secondary endpoints 11

1. Secondary Efficacy Endpoints: Percentage change from baseline in LS BMD at Weeks 26 and 78.
2. Percentage change from baseline in total hip BMD (TH-BMD) and femoral neck BMD (FM-BMD) at Weeks 26, 52, and 78.
3. Secondary PD Endpoints: Percentage change from baseline in sCTX and procollagen type 1 N-terminal propeptide (P1NP) at Weeks 26 and 52.
4. Maximum percentage change from baseline in sCTX at Week 26.
5. AUEC of P1NP over the initial 6-month period (from Day 1 to Week 26 [predose]).
6. Secondary PK Endpoints: Maximum observed serum concentration (Cmax) of denosumab after the first administration (over the initial 6 month period [from Day 1 to Week 26 (predose)]).
7. Trough serum concentration (Ctrough) of denosumab, predose and at Weeks 26, 52, and 78.
8. Secondary Safety Endpoints: The safety and tolerability profile of participants will be assessed by the following parameters up to Weeks 52 and 78, and additionally through the whole study period for adverse events (AEs): Rate of AEs, serious adverse events (SAEs), and adverse reactions.
9. Changes in safety clinical laboratory tests (hematology, chemistry, coagulation, and urinalysis [routine and microscopic]).
10. Changes in vital signs, 12-lead electrocardiogram (ECG), and physical examination findings.
11. Secondary Immunogenicity Endpoint: The rate of positive antidrug antibody (ADA) (the rate of positive neutralizing antibodies [NAbs] may be analyzed) up to Weeks 26, 52, and 78.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Xentria Inc.

Sponsor organisation

Xentria Inc.

Address

2071 North Southport Avenue Suite 201

City

Chicago

Postcode

60614-4015

Country

United States

Scientific contact point

Organisation

Xentria Inc.

Contact name

Tom Matthews

Public contact point

Organisation

Xentria Inc.

Contact name

Noopur Singh

Third parties 3

Locations

3 EU/EEA countries · 33 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications