Comparative efficacy, safety, pharmacokinetic, and immunogenicity study of LY06006 and EU-Prolia in postmenopausal women with osteoporosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Shandong Boan Biotechnology Co. Ltd., Shandong Boan Biotechnology Co. Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Phenomena and Processes [G] - Musculoskeletal and Neural Physiological Phenomena [G11]

Trial duration

26 Apr 2023 → 17 Jun 2025

Decision date (initial)

2024-11-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Shandong Boan Biotechnology Co., Ltd.

External identifiers

EU CT number

2024-513591-18-00

EudraCT number

2022-002312-23

ClinicalTrials.gov

NCT05853354

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Pharmacodynamic, Others, Safety

All regions: To demonstrate equivalent efficacy between LY06006 and EU-Prolia, in terms of BMD in female participants with postmenopausal osteoporosis.
For EU filing only: To demonstrate similar PD between LY06006 and EU-Prolia, in terms of the bone resorption marker sCTX in female participants with postmenopausal osteoporosis.

Secondary objectives 5

1. To provide additional comparative efficacy data of LY06006 with EU-Prolia in female participants with postmenopausal osteoporosis
2. To provide additional comparative PD data on LY06006 with EU-Prolia in female participants with postmenopausal osteoporosis
3. To evaluate the safety of LY06006 compared to EU-Prolia in female participants with postmenopausal osteoporosis
4. To evaluate the PK profile of LY06006 compared to EU-Prolia in female participants with postmenopausal osteoporosis
5. To evaluate the immunogenicity of LY06006 compared to EU-Prolia in female participants with postmenopausal osteoporosis

Conditions and MedDRA coding

Postmenopausal osteoporosis

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency, Pharmaceutical And Medical Devices Evaluation Center

Plan to share IPD

No

IPD plan description

NA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Participant is ≥ 55 to ≤ 90 years of age inclusive, (upper age limit of 75 years inclusive, for participants in Czech Republic only), at the time of signing the informed consent.
2. Participant is an ambulatory postmenopausal woman (defined as lack of menstrual period for at least 12 months prior to Screening Visit, for which there is no other obvious pathological or physiological cause). - Serum FSH test can be done at the Screening Visit in case of uncertainty (for participants to be enrolled in the study in Bulgaria, FSH test is mandatory. FSH levels should be above the cut-off for postmenopausal women, as provided by the central laboratory). - Female participants who underwent bilateral oophorectomy (with or without hysterectomy) at least 6 weeks prior to the Screening Period are eligible to participate.
3. Participant is diagnosed with osteoporosis, with absolute BMD consistent with a T-score of ≤ -2.5 and ≥ -4.0 at the lumbar spine (L1-L4 region) as measured by DXA at the Screening Visit.
4. Participant has at least two lumbar vertebrae in L1-L4 region and one hip evaluable by DXA for BMD measurement at the Screening Visit.
5. Participant has body weight ≥ 50 kg and ≤ 90 kg at Screening.
6. Participant is able to read and understand, and willing to provide signed informed consent as described in Appendix 1, Section 10.1.3 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Exclusion criteria 30

1. Participant has a history of any severe or more than two moderate vertebral fractures as determined by central reading of lateral spine X-ray at Screening Visit.
2. Participant has any malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5 years.
3. Participant has known history of liver cirrhosis.
4. Participant has known history of hepatitis B, hepatitis C, or HIV infection, or an active infection including, but not limited to SARS-CoV-2, tests positive for hepatitis B (positive HBsAg, positive anti-HBc with negative anti-HBs), hepatitis C (hepatitis C antibody), or HIV antibody during the Screening Period.
5. Participant has oral or dental conditions: a. Prior history or current evidence of osteomyelitis or osteonecrosis of the jaw. b. Active dental or jaw condition which requires oral surgery. c. Invasive dental procedure planned during the study or within the past 6 months (e.g., tooth extraction, dental implants, oral surgery). d. Non-healed dental or oral surgery. e. Active periodontal disease. f. Poor oral hygiene.
6. Participant has a history of major surgery within 8 weeks prior to the Screening Period or planned, anticipated major surgery during the study.
7. Participant has a history and/or presence of significant cardiac disease or ECG abnormalities indicating significant risk for participating in the study as judged by the Investigator.
8. Participant shows contraindications to denosumab therapy (e.g., hypocalcemia), or calcium or vitamin D supplementation before starting study intervention administration.
9. Participant requires ongoing use of any osteoporosis treatment (other than calcium and vitamin D supplements).
10. Participant has a history and/or presence of hip fracture.
11. Participant has a history and/or presence of atypical femur fracture.
12. Participant presents with any active healing fracture, per assessment of the Investigator.
13. Participant has a history of bilateral hip replacement (unilateral is allowed if the other hip is evaluable by DXA).
14. Participant has history and/or presence of osteonecrosis of the external auditory canal.
15. Evidence of any of the following conditions which may affect BMD or interfere with the interpretation of the findings: a. Participant has a history of bone disease e.g., osteomalacia, osteopetrosis, Paget's disease, or osteogenesis imperfecta. b. Participant has a history of metabolic or other endocrinologic diseases such as Cushing's disease, hyperprolactinemia, hypopituitarism, acromegaly, malabsorption syndrome (or any gastrointestinal disorders associated with malabsorption, e.g., Crohn's disease and chronic pancreatitis). c. Participant has a history of chronic inflammatory diseases, obvious sclerosis, osteophytosis, severe scoliosis, or other degenerative changes due to other co-morbidities. d. Participant has a history or current hyperparathyroidism or hypoparathyroidism. Note: Mild non-clinically significant secondary hyperparathyroidism may be acceptable upon discussion with the Medical Monitor. e. Participant has current uncontrolled hyperthyroidism or hypothyroidism. Note: Participants with hypothyroidism who are on stable thyroid hormone replacement therapy may be allowed per the following criteria: • If TSH level is within normal range, the participant is eligible. • If TSH level is elevated (> upper limit of normal and ≤ 10.0 µIU/mL) and serum free T4 is within normal range, the participant is eligible. • If a marginally low TSH level results from therapy , the participant may be enrolled after discussion with the Medical Monitor. Note: 2) If TSH is marginally out of normal range, serum free T4 is within normal range, and there are no plausible medical conditions resulting in the abnormal TSH level, the participant may be enrolled with the approval from the Medical Monitor. f. Participant has other disease conditions where there is bone/joint involvement (e.g., rheumatoid arthritis, ankylosing spondylitis, gout, multiple myeloma, achondroplasia, bone metastases, renal osteodystrophy, osteomyelitis).
16. Participant has hypocalcemia (defined as albumin adjusted serum calcium level < 2.0 mmol/L [8.0 mg/dL]) or hypercalcemia (defined as albumin adjusted serum calcium levels >2.62 mmol/L [10.50 mg/dL]).
17. Participant has vitamin D deficiency (defined as 25-hydroxy vitamin D level < 20 ng/mL [< 50 nmol/L]). Note: Oral replenishment of vitamin D is permitted at the discretion of the Investigator and in accordance with local standard of care during the Screening Period. Participants can be enrolled if a repeat test (post supplementation) prior to enrollment shows corrected 25-hydroxy vitamin D level ≥ 20 ng/mL (≥ 50 nmol/L).
18. Use of any of the below medications that can affect BMD: a. Denosumab used at any time prior to Screening Visit. b. Oral bisphosphonates at any dose for osteoporosis treatment: • Used for > 3 years cumulatively at Screening Visit. • At any dose used within 1 year prior to Screening Visit (if ≤ 3 years of use cumulatively). c. Intravenous bisphosphonate at any dose within 5 years prior to Screening Visit. d. PTH or PTH analogues at any dose within 2 years prior to Screening Visit. e. Systemic HRT (oral or transdermal estrogen), SERMs, tibolone, aromatase inhibitors, or androgens at any dose within 1 year prior to Screening Visit. Note: Exceptionally, non-systemic vaginal estrogen treatment is permitted. f. Calcitonin, or its derivatives, and calcimimetics (such as cinacalcet or etelcalcetide) at any dose within 12 months prior to Screening Visit. g. Calcitriol, paricalcitol, alfacalcidol, or eldecalcitol within 3 months of the Screening Visit. h. Fluoride or strontium at any dose at any time prior to Screening Visit. i. Romosozumab or cathepsin K inhibitors received at any time prior to Screening Visit. j. Systemic glucocorticoids (≥ 5 mg prednisone or equivalent per day for more than 10 days or cumulative ≥ 50 mg) within 3 months prior to Screening Visit. k. If the participant is currently on proton pump inhibitors (PPIs) and will continue to use PPIs while on the study, the total of the chronic use of PPIs exceeds 24 months or had past use of PPIs for more than 24 month AND within 3 months prior to Screening Visit. If the participant is currently on proton pump inhibitors (PPIs) and will continue to use PPIs while on the study, the total of the chronic use of PPIs exceeds 24 months or had past use of PPIs for more than 24 month AND within 3 months prior to Screening Visit.
19. Participant is receiving or has received another investigational product within 1 month or 5 half-lives of the other investigational product, whichever is longer, before study intervention administration in this study.
20. Participant has DXA measurements where: a. Height, weight, or girth measurements may preclude accurate DXA measurements in the Investigator’s opinion. b. BMD absolute value is consistent with a T-score < -4.0 at the total hip or femoral neck.
21. Participant has severe renal impairment (defined as participant in dialysis or with an eGFR < 30 mL/min per MDRD formula).
22. Participant has inadequate hepatic function (ALT and/or AST ≥ 2 × ULN).
23. Participant presents with clinically significant leukopenia, neutropenia, or anemia as judged by the Investigator.
24. Participant has a known intolerance to calcium or vitamin D supplements.
25. Participant has a history of prescription drug abuse or any illicit drug use within 6 months prior to Screening Visit.
26. Participant has a history of alcohol abuse (defined as consuming more than 3 drinks on any day or more than 7 drinks per week) according to medical history within 6 months prior to Screening Visit.
27. Participant is a smoker or has used nicotine and nicotine-containing products within 12 months of Screening Visit.
28. Participant has a known sensitivity to mammalian cell-derived drug products and/or a history of hypersensitivity to any of the ingredients of study interventions.
29. Participant is immunosuppressed for any reason.
30. Participant has any other conditions including clinically significant medical conditions/disorders/diseases, psychiatric status, or laboratory abnormalities that in the opinion of the Investigator might interfere with the participant’s ability to participate in the study, would pose a risk to the participant’s safety, or interfere with the study evaluation, procedure, or completion.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Information is not publicly available

Secondary endpoints 19

1. %CfB in lumbar spine BMD at Month 6
2. %CfB in total hip BMD at Months 6 and 12
3. %CfB in femoral neck BMD at Months 6 and 12
4. %CfB in sCTX at Months 0.5, 1, 2, 3, 6, 9, and 12
5. %CfB in sP1NP at Months 1, 6, and 12
6. AEs, including SAEs
7. Vital signs
8. Physical and dental examination
9. Clinical laboratory tests (hematology, clinical chemistry, and urinalysis)
10. 12-lead ECG
11. Injection site reaction assessment
12. Serum drug concentrations at baseline and at Months 0.5, 1, 2, 3, 6, 9, and 12
13. Incidence of ADAs at baseline and at Months 0.5, 1, 2, 3, 6, 9, and 12
14. Incidence of NAbs at baseline and at Months 0.5, 1, 2, 3, 6, 9, and 12
15. %CfB (Month 12) in sCTX at Month 18
16. %CfB (Month 12) in sP1NP at Month 18
17. Serum drug concentrations at baseline (Month 12) and Months 15 and 18
18. Incidence of ADAs at baseline (Month 12), and Months 15 and 18
19. Incidence of NAbs at baseline (Month 12) and at Months 15 and 18

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Shandong Boan Biotechnology Co. Ltd.

Sponsor organisation

Shandong Boan Biotechnology Co. Ltd.

Address

No 39 Keji Avenue, High Tech Zone High Tech Zone

City

Yantai

Postcode

264000

Country

China

Scientific contact point

Organisation

Shandong Boan Biotechnology Co. Ltd.

Contact name

Ying Dong

Public contact point

Organisation

Shandong Boan Biotechnology Co. Ltd.

Contact name

Ying Dong

Third parties 5

Shandong Boan Biotechnology Co. Ltd.

Sponsor organisation

Shandong Boan Biotechnology Co. Ltd.

Address

No 39 Keji Avenue, High Tech Zone High Tech Zone

City

Yantai

Postcode

264000

Country

China

Locations

3 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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