臨床研究等提出・公開システム

A randomized, double-blind, multicenter integrated phase I/III study in postmenopausal women with osteoporosis to compare the pharmacokinetics, pharmacodynamics, efficacy, safety and immunogenicity of GP2411 (proposed biosimilar denosumab) and Prolia (EU-authorized).

Study investigating PK, PD, efficacy, safety, and immunogenicity of biosimilar denosumab (GP2411) in patients with postmenopausal osteoporosis.

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CT.gov English: Baseline characteristics page 13 参照。

CT.gov English: ”Participant flow” Page 11～12 参照。

CT.gov English:” Adverse events"　page 39～46 参照。

CT.gov English:” Outcome Measures"　page 14～19 参照。

CT.gov English:” 6.Secondary"　page 19～39 参照。

Conclusion: In conclusion, the study showed that there are no clinically meaningful differences between GP2411 andEU-Prolia in the treatment of women with PMO over 78 weeks: • Clinical efficacy, PD and PK similarity were demonstrated. • Likewise, the immunogenicity, safety and tolerability comparison did not suggest any relevant differences between GP2411 and EU-Prolia. • The switch from the originator (EU-Prolia) to the proposed biosimilar GP2411 did not result in increased immunogenicity compared with continued EU-Prolia treatment.

Yes

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

PAREXEL International

18F Tradepia Yodoyabashi Bldg., 2-5-8 Imabashi, Chuo-ku, Osaka

shigenori.ito@parexel.com

PAREXEL International

18F Tradepia Yodoyabashi Bldg., 2-5-8 Imabashi, Chuo-ku, Osaka

+81-6-6201-6080

shigenori.ito@parexel.com

completed

Dec. 24, 2019

Interventional

Allocation: Randomized at 1:1 ratio Intervention Model: Parallel Assignment Masking: Triple (Participant, Investigator, Outcomes Assessor) Masking Description: double blind Primary Purpose: Treatment

treatment purpose

3

-Postmenopausal women, diagnosed with osteoporosis
-Aged >_ 55 and _< 80 years at screening
-Body weight >_ 50 kg and _< 90 kg at screening
-Absolute bone mineral density consistent with T-score _< -2.5 and >_ -4.0 at the lumbar spine as measured by DXA
-At least two vertebrae in the L1-L4 region and at least one hip joint are evaluable by DXA

-Previous exposure to denosumab (Prolia, Xgeva, or biosimilar denosumab)
-History and/or presence of one severe or more than two moderate vertebral fractures or hip fracture
-History and/or presence of bone metastases, bone disease or metabolic disease
-Ongoing use of any osteoporosis treatment or use of prohibited treatment
-Other bone active drugs
-History and/or current hypoparathyroidism or hyperparathyroidism, hypocalcemia or hypercalcemia

Other Inclusion/exclusion criteria may apply

Female

Postmenopausal Osteoporosis

investigational material(s)
Generic name etc : GP2411 ( proposed biosimilar denosumab)
INN of investigational material : Denosumab
Therapeutic category code : 399 Agents affecting metabolism, n.e.c.
Dosage and Administration for Investigational material : GP2411 60 mg/mL subcutaneously once every six months.

control material(s)
Generic name etc : Prolia
INN of investigational material : Denosumab
Therapeutic category code : 399 Agents affecting metabolism, n.e.c.
Dosage and Administration for Investigational material : Prolia 60 mg/mL subcutaneously once every six months

efficacy
pharmacokinetics
pharmacodynamics
Treatment Period(Day 1-Week 52)
- Percent change from baseline (%CfB) in lumbar spine BMD (LS-BMD) at Week 52
AUEC after first dose, of %CfB in serum CTX
- Serum PK parameters AUCinf and Cmax after first dos

safety
pharmacokinetics
pharmacodynamics
other
Treatment Period 2 (Week 52 - Week 78)
- %CfB in LS-BMD, FN-BMD, TH-BMD at Week 78
- PD markers: CTX and PINP serum concentrations as per visit schedule from Week 52 up to Week 78
- Safety: fractures, vital signs, laboratory safety assessments, injection site reactions, ECG, occurrence of AEs and serious AEs from Week 52 up to Week 78
- Immunogenicity: Development of binding and neutralizing anti-drug antibodies (ADAs) from Week 52 up to Week 78
- Denosumab serum concentrations as per visit schedule from Week 52 up to Week 78

Oct. 25, 2019