AzTrials
AzTrials

Osteogenesis Imperfecta (OI)Phase 3NCT03638128

Open-label Extension of Study 20130173 of Denosumab in Children and Young Adults With Osteogenesis Imperfecta

A Phase 3 study testing Denosumab and Alternative osteoporosis medications in people with Osteogenesis Imperfecta (OI), run by Amgen at 22 sites in 12 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

To evaluate long-term safety of denosumab in children/young adults with pediatric osteogenesis imperfecta (OI) who completed the prior study 20130173 (NCT02352753). Read more about this study

Who is it for?
Any age
Conditions the study is for
Osteogenesis Imperfecta (OI)
What is being tested?
Denosumab and Alternative osteoporosis medications
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
75 participants
Where
22 sitesin 12 countries
Study dates
26 Jul 2018to 28 Mar 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Subject has provided informed consent/assent prior to initiation of any Study 20170534 specific activities/procedures. Subject's legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated.
  • Subject is currently/was enrolled in Study 20130173 and
  • completed the 20130173 End of Study (EOS) visit (regardless of completing or ending investigational product early) OR
  • did not reconsent/reassent to transition to 3-month dosing regimen on Study 20130173 OR
  • early terminated from Study 20130173 as a result of meeting bone mineral density (BMD) Z-score investigational product stopping criteria.

Who cannot join

  • Treatment with any prohibited proscribed medications while receiving denosumab. Eligibility into study treatment with alternative osteoporosis medication/s of investigator's choice, follow guidelines per the specific alternative osteoporosis medication/s selected. For subjects off-treatment (observation only), no prohibited medications apply.
  • Subjects currently receiving treatment in another investigational device or drug study other than Study 20130173. Other investigational procedures while participating in this study are excluded.
  • For subjects expected to receive investigational product (denosumab) at study day 1: Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 5 months after the last dose of denosumab. Females of childbearing potential (Tanner Stage greater than or equal to 2) should only be included in the study after a negative highly sensitive urine or serum pregnancy test. For study treatment with alternative osteoporosis medication/s of investigator's choice, follow guidelines per the specific alternative osteoporosis medication/s selected. For Subjects off-treatment (observation only), no exclusion applies.
  • For subjects expected to receive investigational product (denosumab) at study day 1: Female subjects of childbearing potential unwilling to practice true sexual abstinence (refrain from heterosexual intercourse) or use 1 highly effective method of contraception during treatment and for an additional 5 months after the last dose of investigational product (denosumab). For study treatment with alternative osteoporosis medication/s of investigator's choice, follow contraception guidelines per the specific alternative osteoporosis medication/s selected. For subjects not receiving any investigational product (observation only), no contraception required.
  • History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.

Trial locations and contacts

22 sites in 12 countries.

22 sites in 12 countries

United Kingdom4 sites
  • Birmingham Childrens Hospital

    Birmingham, B4 6NH

  • Bristol Royal Hospital for Children

    Bristol, BS2 8AE

  • Royal Hospital for Children

    Glasgow, G51 4TF

  • Sheffield Childrens Hospital

    Sheffield, S10 2TH

Other trials in United Kingdom

Canada3 sites
  • Shriners Hospital for Children

    Montreal, Quebec, H4A 0A9

  • Childrens Hospital of Eastern Ontario

    Ottawa, Ontario, K1H 8L1

  • The Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

Other trials in Canada

United States2 sites
  • Indiana University - Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Childrens Hospital of Los Angeles

    Los Angeles, California, 90027

Other trials in United States

Australia2 sites
  • Perth Childrens Hospital

    Nedlands, Western Australia, 6909

  • The Childrens Hospital at Westmead

    Westmead, New South Wales, 2145

Other trials in Australia

Czechia2 sites
  • Fakultni nemocnice Plzen

    Pilsen, 305 99

  • Thomayerova nemocnice

    Prague, 140 59

Other trials in Czechia

France2 sites
  • Centre Hospitalier Universitaire de Bordeaux - Hopital Pellegrin

    Bordeaux, 33076

  • Hopital Necker Enfants Malades

    Paris, 75743

Other trials in France

Spain2 sites
  • Hospital Sant Joan de Deu

    Esplugues de Llobregat, Catalonia, 08950

  • Hospital Universitari i Politecnic La Fe

    Valencia, Valencia, 46026

Other trials in Spain

Belgium1 site
  • Universite Catholique de Louvain Cliniques Universitaires Saint Luc

    Brussels, 1200

Other trials in Belgium

Germany1 site
  • Uniklinik Köln

    Cologne, 50931

Other trials in Germany

Hungary1 site
  • Semmelweis Egyetem

    Budapest, 1094

Other trials in Hungary

Italy1 site
  • Azienda Ospedaliera Policlinico Umberto I

    Roma, 00161

Other trials in Italy

Poland1 site
  • SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi

    Lodz, 91-738

Other trials in Poland

About this study

Official title: Multicenter, Single-arm Open-label Extension Study to Assess Long-term Safety and Efficacy of Current or Prior Treatment With Denosumab in Children/Young Adults With Osteogenesis Imperfecta

To evaluate long-term safety of denosumab in children/young adults with pediatric osteogenesis imperfecta (OI) who completed the prior study 20130173 (NCT02352753).

Read the detailed description

All participants who completed the prior denosumab study 20130173 (NCT02352753) were offered participation in this study (20170534). Participants could continue to receive denosumab once every 3 months (Q3M) or could receive denosumab once every 6 months (Q6M) or off-treatment observation only at the investigator's discretion. The study design allowed subjects to discontinue denosumab, resume denosumab, initiate alternative osteoporosis medication, discontinue alternative osteoporosis medication, or receive no treatment (observation only) at any time. Therefore results of this study were analyzed according to both baseline treatment and subsequent treatment trajectories.

Being tested
Denosumab, Alternative osteoporosis medications
Keywords
OI, Bone.
Medical subject headings
Osteogenesis Imperfecta

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DenosumabDrug

    Also called Prolia

    Solution for injection

  • Alternative osteoporosis medicationsDrug

    Alternative osteoporosis medication/s at the discretion of the investigator.

Study groups in NCT03638128
Study groupRoleWhat they receive
Alternative Medications / ObservationalOtherParticipants who received non-denosumab alternative therapy during the study or who were not receiving any medication at baseline. Alternative osteoporosis medication(s) were determined at the investigator's discretion and per standard of care and local guidelines.
Receives: Drug: Alternative osteoporosis medications
Denosumab 1 mg/kg Q6MExperimentalParticipants who received at least 1 dose of 1 mg/kg denosumab administered once every 6 months (Q6M) by subcutaneous injection, but no Q3M denosumab during this study.
Receives: Drug: Denosumab
Denosumab 1 mg/kg Q3MExperimentalParticipants who received at least one dose of 1 mg/kg denosumab administered once every 3 months (Q3M) by subcutaneous injection during this study.
Receives: Drug: Denosumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest

    A Serious Adverse Event is defined as any untoward medical occurrence that met at least 1 of the following serious criteria:

    • Resulted in death (fatal)
    • Immediately life-threatening
    • Required in-patient hospitalization or prolongation of existing hospitalization
    • Resulted in persistent or significant disability/incapacity
    • Was a congenital anomaly/birth defect
    • Other medically important serious event that may have jeopardized the participant or require medical or surgical intervention to prevent 1 of the outcomes listed above.

    Adverse events of special interest included hypocalcemia, hypersensitivity, bacterial cellulitis, osteonecrosis of the jaw (ONJ), hypercalcemia, and typical osteogenesis imperfecta (OI) femur fractures.

    Measured: From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.

  2. Number of Participants With Anti-denosumab Antibodies

    Blood samples were collected (from denosumab treated participants only) for the measurement of anti-denosumab binding antibodies. Samples positive for anti-denosumab binding antibodies were further tested for neutralizing antibodies.

    Measured: From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months

  3. Number of Participants With Clinical Laboratory Toxicities Grade ≥ 3

    Laboratory abnormalities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0. The grades refer to the severity of the finding:

    Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe or medically significant; Grade 4 = Life-threatening consequences, urgent intervention indicated.

    Measured: From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months

  4. Number of Participants With Clinically Significant Vital Sign Findings

    Vital sign measurements included systolic and diastolic blood pressure, heart rate, respiratory rate, and temperature. The investigator assessed vital sign results and determined whether any abnormal changes represented a clinically significant change from the participant's baseline values.

    Measured: From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months

  5. Number of Participants With Metaphyseal Index Z-score Above Age-appropriate Normal Range

    Anteroposterior radiographs of both knees (unless prohibited by the presence of hardware such as implants) were used to calculate the metaphyseal index Z-score of each knee in participants with open growth plates; the knee selected for assessment during the study was the knee with the higher Z-score at baseline. The metaphyseal index (MI) was calculated by the central imaging vendor as the ratio of femoral width over distal femoral growth plate width, and the Z-score for each participant, relative to the participant's age as:

    MI Z-score = (participant value - mean)/SD, where mean and standard deviation (SD) are the corresponding values based on a reference population for the participant's age group at the time of the assessment.

    Metaphyseal index Z-score above age-appropriate normal range is defined as a MI Z-score > 2.

    Measured: Baseline, month 12 and month 24

  6. Number of Participants With Abnormal Molar Eruption of the First or Second Molar Based on Radiological Findings

    Participants underwent a visual inspection under natural light for the presence of the first and second molars. Participants were referred to a dentist to perform radiographic assessment of the unerupted molar(s) if:

    • A participant was age 7 to 12 years and appeared to have an unerupted upper or lower first molar (ie, not all 4 first molars were visible/detectable).
    • A participant was age 13 years or older and appeared to have an unerupted upper or lower (first or) second molar (ie, not all 4 first molars and all 4 second molars were visible/detectable).

    Abnormal molar eruptions includes the number of participants 7 to 12 years of age with 1st unerupted or partially erupted molars and participants 13 years of age or older with 2nd unerupted or partially erupted molars.

    Measured: Baseline, month 12, and month 24

  7. Percent Change From Baseline in Mandibular Shaping Parameters

    Lateral cephalogram was performed to enable assessment of mandibular shaping. The lateral cephalogram is a profile X-ray of the skull and soft tissues and is used to assess the relation of the teeth in the jaws, the relation of the jaws to the skull, and the relation of the soft tissues to the teeth and jaws.

    The following anatomical angles and dimensions were measured to evaluate the correct proportions of the mandible and its position relative to the skull/maxilla: Gonial angle; Sella-Nasion-A Point Angle (SNA angle); Sella-Nasion-B Point Angle (SNB angle); and A Point - Nasion-B Point Angle (ANB Angle).

    Measured: Baseline and month 12 and month 24

Secondary outcomes (3)
  1. Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score

    Bone densitometry assessments of the lumbar spine were performed using dual X-ray absorptiometry (DXA).

    The Z-score indicates the number of standard deviations away from the mean of an average person of the same age, sex, race, and weight. A Z-score of 0 is equal to the mean of the matched population, negative Z-scores indicate a BMD lower than the mean of the matched population, and positive Z-scores indicate a higher BMD than that of the matched population. A positive change from baseline indicates an improvement in lumbar spine BMD.

    Measured: Baseline and months 6, 12, and 24

  2. Change From Baseline in Total Hip BMD Z-score

    Bone densitometry assessments of the hip were performed using dual X-ray absorptiometry (DXA).

    The Z-score indicates the number of standard deviations away from the mean of an average person of the same age, sex, race, and weight. A Z-score of 0 is equal to the mean of the matched population, negative Z-scores indicate a BMD lower than the mean of the matched population, and positive Z-scores indicate a higher BMD than that of the matched population. A positive change from baseline indicates an improvement in total hip BMD.

    Measured: Baseline, months 6, 12, and 24

  3. Change From Baseline in Femoral Neck BMD Z-score

    Bone densitometry assessments of the femoral neck were performed using dual X-ray absorptiometry (DXA).

    The Z-score indicates the number of standard deviations away from the mean of an average person of the same age, sex, race, and weight. A Z-score of 0 is equal to the mean of the matched population, negative Z-scores indicate a BMD lower than the mean of the matched population, and positive Z-scores indicate a higher BMD than that of the matched population. A positive change from baseline indicates an improvement in femoral neck BMD.

    Measured: Baseline and months 6, 12, and 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Aug 2018
  2. Study start26 Jul 2018
  3. Primary completion28 Mar 2022
  4. Study completion28 Mar 2022

Why it stopped: The study was stopped earlier than planned due to safety concerns about high levels of calcium in the blood of the participants

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
75 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03638128
Sponsor's protocol ID
20170534
Other IDs
2018-000550-21, 2018
Status last verified
Nov 2022
First submitted
21 Jun 2018
Last updated
20 Dec 2022
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Denosumab and Alternative osteoporosis medications in people with Osteogenesis Imperfecta (OI), run by Amgen at 22 sites in 12 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 20 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United Kingdom, Canada, United States, Australia, Czechia and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest (time frame: From enrollment to end of study, including 24 weeks after last dose of denosumab for participants who received denosumab; the maximum time on study was 24 months.). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2022.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in