Clinical trial NCT03638128: Open-label Extension of Study 20130173 of Denosumab in Children and Young Adults With Osteogenesis Imperfecta
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Osteogenesis Imperfecta (OI)
Keywords: OI
Bone.
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2018-08-20
Enrollment: 75
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Number of Participants With Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest
timeFrame: 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.
measure: Number of Participants With Anti-denosumab Antibodies
timeFrame: 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
measure: Number of Participants With Clinical Laboratory Toxicities Grade ≥ 3
timeFrame: 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
measure: Number of Participants With Clinically Significant Vital Sign Findings
timeFrame: 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
measure: Number of Participants With Metaphyseal Index Z-score Above Age-appropriate Normal Range
timeFrame: Baseline, month 12 and month 24
measure: Number of Participants With Abnormal Molar Eruption of the First or Second Molar Based on Radiological Findings
timeFrame: Baseline, month 12, and month 24
measure: Percent Change From Baseline in Mandibular Shaping Parameters
timeFrame: Baseline and month 12 and month 24
Secondary outcomes:
measure: Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score
timeFrame: Baseline and months 6, 12, and 24
measure: Change From Baseline in Total Hip BMD Z-score
timeFrame: Baseline, months 6, 12, and 24
measure: Change From Baseline in Femoral Neck BMD Z-score
timeFrame: Baseline and months 6, 12, and 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Childrens Hospital of Los Angeles
state: California
city: Indianapolis
country: United States
facility: Indiana University - Riley Hospital for Children
state: Indiana
city: Westmead
country: Australia
facility: The Childrens Hospital at Westmead
state: New South Wales
city: Nedlands
country: Australia
facility: Perth Childrens Hospital
state: Western Australia
city: Bruxelles
country: Belgium
facility: Universite Catholique de Louvain Cliniques Universitaires Saint Luc
city: Ottawa
country: Canada
facility: Childrens Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Shriners Hospital for Children
state: Quebec
city: Plzen
country: Czechia
facility: Fakultni nemocnice Plzen
city: Praha 4
country: Czechia
facility: Thomayerova nemocnice
city: Bordeaux Cedex
country: France
facility: Centre Hospitalier Universitaire de Bordeaux - Hopital Pellegrin
city: Paris Cedex 15
country: France
facility: Hopital Necker Enfants Malades
city: Köln
country: Germany
facility: Uniklinik Köln
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Roma
country: Italy
facility: Azienda Ospedaliera Policlinico Umberto I
city: Lodz
country: Poland
facility: SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Deu
state: Cataluña
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
state: Comunidad Valenciana
city: Birmingham
country: United Kingdom
facility: Birmingham Childrens Hospital
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Children
city: Sheffield
country: United Kingdom
facility: Sheffield Childrens Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: