The Use of Steovess/Binosto After Denosumab Discontinuation to Prevent Increase in Bone Turnover

NCT04403698 | Completed Phase 2 Results DMC

• 1 other identifier: BC-6072
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

It is hypothesized that effervescent alendronate will be able to maintain bone turnover markers within the pre-menopausal reference range and thereby reducing the likelihood of bone turnover associated changes (rebound effect), after discontinuation of denosumab treatment in a non-osteoporotic population.

Conditions

Erosive Osteoarthritis

Outcome Measures

Primary Outcomes (2)

• CTX-I (C-terminal Telopeptide of Type I Collagen ) Bone Turnover Marker Levels

  Difference in bone turnover marker C-terminal telopeptide of type I collagen (CTX-I) after 48 weeks. Comparisons made within and between both treatment arms

  48 weeks

• PINP (N-terminal Propeptide of Type I Procollagen) Bone Turnover Marker Levels

  Difference in Bone Turnover Marker N-terminal propeptide of type I procollagen (PINP) After 48 Weeks. Comparisons are made both within and between both treatment arms.

  48 weeks

Secondary Outcomes (4)

• Number of Patients With CTX-I (C-terminal Telopeptide of Type I Collagen )Levels Above the Reference Range at Week 48

  48 weeks

• The Number of Patients PINP (N-terminal Propeptide of Type I Procollagen) Above Reference Range at Week 48

  48 weeks

• Bone Mass Density at the Spine After 48 Weeks

  48 weeks

• Bone Mass Density at the Hip After 48 Weeks

  48 weeks

Study Arms (2)

24 weeks

EXPERIMENTAL

Subject receiving alendronate treatment for 24 weeks (n = 20)

Drug: Alendronate Effervescent Oral Tablet

48 weeks

EXPERIMENTAL

Subject receiving alendronate treatment for 48 weeks (n = 20)

Drug: Alendronate Effervescent Oral Tablet

Interventions

Alendronate Effervescent Oral Tablet DRUG

At the earliest three months but no later than four months after the last denosumab injection, subjects will be randomized to effervescent alendronate administered for either 24 or 48 weeks

24 weeks; 48 weeks

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have completed the 48 weeks of the randomised placebo-controlled study phase followed by the 96 weeks open label denosumab 60 mg SC every 3 months phase. (EudraCT number: 2015-003223-53)
• Last denosumab injection minimal 3 months or maximum 4 months before baseline
• Able and willing to give written informed consent and to comply with the requirements of the study protocol

You may not qualify if:

• Patients with clinically significant hypersensitivity to any of the components of effervescent alendronate.
• Patient who is pregnant or planning pregnancy
• Female subjects who are breast-feeding.
• History of osteonecrosis of the jaw, and/or recent (within 3 months) tooth extraction or other unhealed dental surgery; or planned invasive dental work during the study
• Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
• Hypocalcaemia.
• Oesophageal disease, gastritis, duodenitis, ulcers, or with a recent history (within the previous year) of major gastro-intestinal disease such as peptic ulcer, or active gastro-intestinal bleeding, or surgery of the upper gastro-intestinal tract other than pyloroplasty.
• Abnormalities of the oesophagus and other factors which delay oesophageal emptying such as stricture or achalasia.
• Inability to stand or sit upright for at least 30 minutes.

Sponsors & Collaborators

• University Hospital, Ghent: lead
• Amgen: collaborator
• EffRx Pharmaceuticals SA: collaborator

Study Sites (1)

Ghent University Hospital

Ghent, 9000, Belgium

Location

Related Publications (5)

• Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone. 2008 Aug;43(2):222-229. doi: 10.1016/j.bone.2008.04.007. Epub 2008 Apr 26.

  PMID: 18539106 BACKGROUND

• Brown JP, Roux C, Torring O, Ho PR, Beck Jensen JE, Gilchrist N, Recknor C, Austin M, Wang A, Grauer A, Wagman RB. Discontinuation of denosumab and associated fracture incidence: analysis from the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial. J Bone Miner Res. 2013 Apr;28(4):746-52. doi: 10.1002/jbmr.1808.

  PMID: 23109251 BACKGROUND

• Cummings SR, Ferrari S, Eastell R, Gilchrist N, Jensen JB, McClung M, Roux C, Torring O, Valter I, Wang AT, Brown JP. Vertebral Fractures After Discontinuation of Denosumab: A Post Hoc Analysis of the Randomized Placebo-Controlled FREEDOM Trial and Its Extension. J Bone Miner Res. 2018 Feb;33(2):190-198. doi: 10.1002/jbmr.3337. Epub 2017 Nov 22.

  PMID: 29105841 BACKGROUND

• Freemantle N, Satram-Hoang S, Tang ET, Kaur P, Macarios D, Siddhanti S, Borenstein J, Kendler DL; DAPS Investigators. Final results of the DAPS (Denosumab Adherence Preference Satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women. Osteoporos Int. 2012 Jan;23(1):317-26. doi: 10.1007/s00198-011-1780-1. Epub 2011 Sep 17.

  PMID: 21927922 BACKGROUND

• Hodges LA, Connolly SM, Winter J, Schmidt T, Stevens HN, Hayward M, Wilson CG. Modulation of gastric pH by a buffered soluble effervescent formulation: A possible means of improving gastric tolerability of alendronate. Int J Pharm. 2012 Aug 1;432(1-2):57-62. doi: 10.1016/j.ijpharm.2012.04.073. Epub 2012 May 4.

  PMID: 22564778 BACKGROUND

Limitations and Caveats

The target number of participants was not reached and therefore underpowered. The study should be repeated on a higher number of participants and with a longer follow-up time to estimate clinical consequences on long term.

Results Point of Contact

• Title: Prof. dr. Ruth Wittoek
• Organization: Study Principal Investigator Ghent Universitary Hospital

Ruth.Wittoek@Ugent.be

+329 332 25 20

Study Officials

• Ruth Wittoek, Prof. dr.

  Ghent Universitary Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 40 subjects randomized in 2 groups (n=20). 1 group will receive effervescent alendronate treatment for 24 weeks, the other group will receive the same treatment for 48 weeks.

Study Record Dates

• First Submitted: May 19, 2020
• First Posted: May 27, 2020
• Study Start: November 13, 2019
• Primary Completion: March 9, 2022
• Study Completion: March 9, 2022
• Last Updated: December 13, 2024
• Results First Posted: December 13, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 6 months after publication. Data will stay available for 3 years after publication
• Access Criteria: acces will be provided upon reasonable request from researchers with a sound clinical research question

Locations

BE (1)