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

April 20, 2022 updated by: University Hospital, Ghent

The Use of Buffered Soluble Alendronate 70 mg (Steovess/Binosto) After Denosumab Discontinuation to Prevent Increase in Bone Turnover

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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 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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Ghent, Belgium, 9000
        • Ghent University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 24 weeks
Subject receiving alendronate treatment for 24 weeks (n = 20)
Drug: 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
Experimental: 48 weeks
Subject receiving alendronate treatment for 48 weeks (n = 20)
Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bone turnover marker above the premenopausal reference range at week 48
Time Frame: 48 weeks
the number of patients that maintain C-terminal telopeptide of type I collagen (CTx-I) levels within the premenopausal reference range at week 48
48 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bone turnover marker above the premenopausal reference range at week 12 and week 24
Time Frame: 12, 24 and 48 weeks
The number of patients that maintain CTx-I levels within the premenopausal reference range at week 12 and 24 as well as the changes in CTx-I and N-terminal propeptide of type I procollagen (P1NP) levels from baseline until 12, 24 and 48 weeks
12, 24 and 48 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
BMD changes
Time Frame: 24 and 48 weeks
Other outcomes are changes in T-score at lumbar spine and hip at BMD from baseline to week 24 and week 48.
24 and 48 weeks
Hand radiographic changes
Time Frame: 24 and 48 weeks
The radiographic changes at the finger joints in terms of new erosive joints and changes according to the Ghent University scoring system (GUSS) between W24 and W48 and baseline.
24 and 48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Ghent

Collaborators

Amgen
EffRx Pharmaceuticals

Investigators

  • Principal Investigator: Ruth Wittoek, Prof. dr., Ghent Universitary Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 13, 2019

Primary Completion (Actual)

March 9, 2022

Study Completion (Actual)

March 9, 2022

Study Registration Dates

First Submitted

May 19, 2020

First Submitted That Met QC Criteria

May 25, 2020

First Posted (Actual)

May 27, 2020

Study Record Updates

Last Update Posted (Actual)

April 22, 2022

Last Update Submitted That Met QC Criteria

April 20, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BC-6072

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

All collected IPD that underlie results in a publication will be shared

IPD Sharing Time Frame

6 months after publication. Data will stay available for 3 years after publication

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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