Multicenter Study in Postmenopausal Women With Osteoporosis, ALVOBOND (ALVOBOND)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Osteoporosis, Postmenopausal
• Intervention / Treatment: Biological: AVT03; Biological: Denosumab

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 532
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Roshan Dias; Phone Number: +41786595945; Email: roshan.dias@alvotech.com
• Study Contact Backup: Name: Augustin Ndiaye; Email: augustin.ndiaye@alvotech.com

Study Locations

• South Africa
  • Port Elizabeth, South Africa
    • Investigational Site 2701

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AVT03; AVT03 is the proposed biosimilar for Prolia.	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.
Active Comparator: Prolia	Biological: 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.; Other Names: Prolia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To demonstrate clinical similarity of AVT03 and Prolia® in terms of change in Bone Mineral Density (BMD).	Change in BMD	Month 12
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change from Baseline in LS BMD	Percent change from Baseline in LS BMD at 6 and 18 months	Month 18
Incidence of new morphometric vertebral fractures	Incidence of new morphometric vertebral fractures at 12 and 18 months	Month 12 and 18
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
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
Incidence, nature and severity of adverse events including adverse drug reactions		Month 18
Frequency and severity of injection site reactions		Month 12
Frequency and severity of findings in routine safety parameters		Month 18
Frequency and titer of anti-drug antibodies and frequency of neutralizing antibodies against AVT03 and Prolia		Month 18
Serum trough concentration of AVT03 and Prolia		Month 18

Collaborators and Investigators

• Sponsor: Alvotech Swiss AG
• Investigators: Study Director: Lukasz Jaskiewicz, Alvotech

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2022
• Primary Completion (Estimated): May 12, 2024
• Study Completion (Estimated): October 25, 2024

Study Registration Dates

• First Submitted: May 24, 2022
• First Submitted That Met QC Criteria: May 24, 2022
• First Posted (Actual): May 27, 2022

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Postmenopausal Osteoporosis, Denosumab, Alvotech
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Osteoporosis, Postmenopausal; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: AVT03-GL-C01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes