Multicenter Study in Postmenopausal Women With Osteoporosis, ALVOBOND

Osteoporosis, Postmenopausal Clinical Trial

— ALVOBOND  

Official title:

A Randomized, Double-Blind, Parallel Design, Repeat Dose, 2-arm, Multicenter Study Comparing the Efficacy, Safety, Immunogenicity, and Pharmacokinetic Profiles of AVT03 and US-Prolia® in Postmenopausal Women With Osteoporosis, ALVOBOND

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05395091
• Other study ID #: AVT03-GL-C01
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 23, 2022
• Est. completion date: October 25, 2024

Study information

• Verified date: May 2024
• Source: Alvotech Swiss AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, double-blind, parallel design, repeat dose, 2 arm, multicenter study comparing the efficacy, safety, immunogenicity, pharmacodynamic (PD) and pharmacokinetic (PK) profiles of AVT03 and US-Prolia in postmenopausal women with osteoporosis.

Description:

After the screening activities, eligible subjects were randomized to receive either AVT03 60 mg or Prolia® 60 mg, administered as a subcutaneous (s.c.) injection At Month 12, subjects in AVT03 treatment group will receive a third dose of AVT03 60 mg administered s.c. while subjects in Prolia® treatment group will be re-randomized to receive either Prolia 60 mg or AVT03 60 mg administered as a subcutaneous injection.

Afterwards, the subjects will be followed until the End of Study (EoS) Visit.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 532
• Est. completion date: October 25, 2024
• Est. primary completion date: May 7, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 50 Years and older

Eligibility

1. Postmenopausal women with osteoporosis willing to sign an informed consent form (ICF)and able to undergo protocol related procedures.

2. A baseline dual-energy x-ray absorptiometry (DXA) scan with a T score =-2.5 and

• 4.0 at the LS (L1 to L4)and/or, total hip, and/or femoral neck.

3. Age: =50 years.

4. Female subject is postmenopausal according to 1 of the following criteria:

1. Spontaneous amenorrhea for =12 consecutive months

2. Biochemical criteria of menopause, follicle-stimulating hormone, >40 IU/L except surgically sterile

3. Having had bilateral oophorectomy =6 weeks prior to Screening

5. Willing to receive calcium plus vitamin D supplements.

6. At least 2 consecutive evaluable lumbar vertebrae and at least 1 evaluable hip.

Exclusion Criteria

1. Evidence of clinically relevant pathology, especially prior diagnosis of bone disease, or any uncontrolled condition that will affect bone metabolism

2. History and/or presence of 1 severe or more than 1 moderate vertebral fractures confirmed by x-ray.

3. History of hip fracture

4. Presence of active healing fractures

5. Osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures

6. Evidence of hypo/hypercalcemia at Screening

7. Known vitamin D deficiency

8. Known intolerance to calcium and vitamin D supplement.

Related Conditions & MeSH terms

• Osteoporosis
• Osteoporosis, Postmenopausal

Intervention

Biological:
• AVT03
AVT03 (denosumab) is a recombinant fully human IgG2 monoclonal antibody to RANKL to be administered as a subcutaneous injection. Subjects in this arm will receive AVT03 60mg administered s.c. At Month 12, subjects in the AVT03 arm will receive a third dose of AVT03 60 mg.
• Denosumab
Prolia (denosumab) is a recombinant fully human IgG2 monoclonal antibody to RANKL developed to be administered as a subcutaneous injection. Subjects will receive 60mg of commercially available US-Prolia, administered s.c At Month 12, subjects in the Prolia treatment group will be re-randomized in a 1:1 ratio to receive either: Group 2a: Subjects will receive AVT03 60 mg administered s.c. on Day365. Group 2b: Subjects will receive Prolia 60 mg administered s.c. on Day365.

Locations

Country	Name	City	State
Bulgaria	Investigational Site 3501	Plovdiv
Bulgaria	Investigational Site 3503	Plovdiv
Bulgaria	Investigational Site 3502	Stara Zagora
Czechia	Investigational Site 4201	Praha
Czechia	Investigational Site 4202	Uherské Hradište
Georgia	Investigational Site 9901	Tbilisi
Georgia	Investigational Site 9902	Tbilisi
Georgia	Investigational Site 9903	Tbilisi
Georgia	Investigational Site 9904	Tbilisi
Georgia	Investigational Site 9905	Tbilisi
Georgia	Investigational Site 9906	Tbilisi
Poland	Investigational Site 4803	Bialystok
Poland	Investigational Site 4804	Bialystok
Poland	Investigational Site 4802	Kraków
Poland	Investigational Site 4807	Kraków
Poland	Investigational Site 4806	Lódz
Poland	Investigational Site 4811	Lublin
Poland	Investigational Site 4812	Poznan
Poland	Investigational Site 4801	Skierniewice
Poland	Investigational Site 4805	Swidnik
Poland	Investigational Site 4809	Warsaw
Poland	Investigational Site 4810	Zamosc
South Africa	Investigational Site 2705	Bloemfontein
South Africa	Investigational Site 2714	Cape Town
South Africa	Investigational Site 2707	Centurion
South Africa	Investigational Site 2708	Centurion
South Africa	Investigational Site 2710	Groenkloof
South Africa	Investigational Site 2712	Johannesburg
South Africa	Investigational Site 2702	Kwadukuza
South Africa	Investigational Site 2711	Parow
South Africa	Investigational Site 2701	Port Elizabeth
South Africa	Investigational Site 2706	Pretoria
South Africa	Investigational Site 2713	Pretoria
South Africa	Investigational Site 2703	Worcester

Sponsors (1)

Lead Sponsor	Collaborator
Alvotech Swiss AG

Countries where clinical trial is conducted

Bulgaria,  Czechia,  Georgia,  Poland,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To demonstrate clinical similarity of AVT03 and Prolia® in terms of change in Bone Mineral Density (BMD).	Change in BMD	Month 12
Primary	To demonstrate clinical similarity of AVT03 and Prolia in terms of area under the percent change from Baseline in serum C-telopeptide of type 1 collagen (AUEC of %Cfb sCTX-1)		Month 6
Secondary	Percent change from Baseline in LS BMD	Percent change from Baseline in LS BMD at 6 and 18 months	Month 18
Secondary	Percent change from Baseline in hip and femoral neck BMD	Percent change from Baseline in hip and femoral neck BMD at Month 6, 12 and 18 months	Month 6, Month 12, Month 18
Secondary	Incidence of new morphometric vertebral fractures	Incidence of new morphometric vertebral fractures at 12 and 18 months	Month 12 and 18
Secondary	Percent change from Baseline in sCTX-1	Percent change from Baseline in sCTX-1 at 3, 6, 9, 12 and 18 months	Month 3, Month 6, Month 9, Month 12 and Month 18
Secondary	Incidence, nature and severity of adverse events including adverse drug reactions		Month 18
Secondary	Frequency and severity of injection site reactions		Month 12
Secondary	Frequency and severity of findings in routine safety parameters		Month 18
Secondary	Frequency and titer of anti-drug antibodies and frequency of neutralizing antibodies against AVT03 and Prolia		Month 18
Secondary	Serum trough concentration of AVT03 and Prolia		Month 18