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

NCT ID: NCT04403698

Last Updated: 2024-12-13

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-13

Study Completion Date

2022-03-09

Brief Summary

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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.

Detailed Description

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Denosumab discontinuation is associated with a rebound effect in bone turnover and loss in bone mass density. These changes resulted in an increase of fracture incidence in patients with postmenopausal osteoporosis back to background levels. However, no excess in fracture incidence was observed. Amongst patients who presented with vertebral fractures after treatment discontinuation, there was a slightly higher incidence of multiple vertebral fractures in patients discontinuing Prolia versus those who discontinued the placebo treatment.

A 2 year, randomized, crossover study demonstrated that alendronate intake after discontinuing denosumab treatment, lead to remaining stable bone mass densitometry (BMD) values in postmenopausal women.

In a study within a non-osteoporotic study population, ongoing at our department, increases in bone turnover are to be expected as soon as patients end study participation (i.e. open label treatment with denosumab, Prolia, anti-RANK ligand inhibition).

It is currently recommended that alternative anti-resorptive therapy may be warranted after Prolia discontinuation. One study describes the use of oral alendronate after denosumab therapy to maintain bone mineral density. However, gastro-intestinal upset and tolerability, as well as difficulty in swallowing pills may limit oral alendronate compliance. To attenuate this concern, buffered soluble (effervescent) alendronate 70 mg, developed with the aim to improve the gastrointestinal tolerability through full dissolution of alendronate in buffered palatable solution before ingestion, will be used.

This study wants to provide a follow up and study wether the use of effervescent alendronate after previous denosumab treatment can prevent a rebound effect in bone turnover that is to be expected when denosumab is discontinued. Subjects that completed our erosive hand osteoarthritis (OA) study and therefore discontinued denosumab 60 mg/every 3 months, will receive alendronate. Moreover, the study wants to asses if there is difference between using alendronate for six or twelve months, starting at the earliest three months but no later than four months after the last injection of denosumab.

Conditions

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Erosive Osteoarthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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24 weeks

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

Group Type EXPERIMENTAL

Alendronate Effervescent Oral Tablet

Intervention Type 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

48 weeks

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

Group Type EXPERIMENTAL

Alendronate Effervescent Oral Tablet

Intervention Type 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

Interventions

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Alendronate Effervescent Oral Tablet

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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.
Minimum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role collaborator

EffRx Pharmaceuticals SA

INDUSTRY

Sponsor Role collaborator

University Hospital, Ghent

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ruth Wittoek, Prof. dr.

Role: PRINCIPAL_INVESTIGATOR

Ghent Universitary Hospital

Locations

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Ghent University Hospital

Ghent, , Belgium

Site Status

Countries

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Belgium

References

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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.

Reference Type BACKGROUND
PMID: 18539106 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23109251 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29105841 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21927922 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22564778 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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BC-6072

Identifier Type: -

Identifier Source: org_study_id