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Setrusumab vs Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta (Cosmic)

Primary Purpose

Osteogenesis Imperfecta

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Bisphosphonate
Setrusumab
Sponsored by
Ultragenyx Pharmaceutical Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteogenesis Imperfecta

Eligibility Criteria

2 Years - 6 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Male or female 2 to < 7 years of age at time of informed consent Clinical diagnosis of OI Types I, III, or IV confirmed by identification of genetic mutation in COL1A1 or COL1A2 History of ≥ 1 fracture in the past 12 months, ≥ 2 fractures in the past 24 months, or ≥ 1 femur, tibia, or humerus fracture in the past 24 months Any prior exposure to, or currently receiving, IV-bisphosphonate therapy for treatment of OI Serum 25-hydroxyvitamin D level ≥ 20 ng/mL at the Screening visit. If 25-hydroxyvitamin D levels are below 20 ng/mL, the subject may be rescreened after a minimum of 14 days of vitamin D supplementation as directed by the Investigator Exclusion Criteria: Contraindication for the use of IV bisphosphonates based on clinical judgment of the Investigator History of skeletal malignancies or bone metastases at any time History of neural foraminal stenosis (except if due to scoliosis) Clinical manifestations of Chiari malformation or basilar invagination. Presence of any other neurologic disease that has been clinically unstable within past 2 years requires review by the Medical Monitor. History of or current uncontrolled concomitant diseases that may impact bone metabolism, such as hypo/hyperparathyroidism, abnormal thyroid function, nephrotic syndrome, or Stage IV/V renal disease Any skeletal condition (other than OI) leading to bone deformity and/or increased risk of fractures, such as rickets, osteopetrosis, idiopathic juvenile osteoporosis, or skeletal dysplasia History of known cardiovascular disease such as coronary artery anomaly, Kawasaki disease, myocarditis, cardiomyopathy, myocardial infarction, stroke, or thromboembolic disease. Individuals with other congenital or acquired cardiovascular disease necessitating echocardiogram require Medical Monitor review. Investigators should consider whether the potential benefits of treatment outweigh the potential risks in patients with cardiovascular risk factors such as confirmed arterial hypertension. Hypocalcemia, defined as serum calcium levels below the age-adjusted normal limit reference ranges after a recommended ≥ 4 hour fast, at Screening Estimated glomerular filtration rate <=35 mL/min/1.73 m2 at Screening Prior treatment with growth hormone, denosumab, anti-sclerostin antibody, or other anabolic or anti-resorptive medications impacting the bone (other than bisphosphonates) at any time History of external radiation therapy Known hypersensitivity to setrusumab or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects Presence or history of any condition that, in the view of the Investigator, would interfere with participation, pose undue risk, or would confound interpretation of results Use of any investigational product or investigational medical device within 4 weeks or 5 half-lives (whichever is longer) of investigational drug prior to Screening, or during the study (per discretion of the Investigator in consultation with the Medical Monitor) Concurrent participation in another clinical study without prior approval from the study Medical Monitor

Sites / Locations

  • Phoenix Children's Hospital
  • Childrens Hospital LARecruiting
  • Children's Hospital ColoradoRecruiting
  • Yale New Haven HospitalRecruiting
  • Nemours/ Alfred i. duPoint Hospital for ChildrenRecruiting
  • Children's National Hospital DC
  • University of South FloridaRecruiting
  • Shriners Hospitals for Children ChicagoRecruiting
  • University of Missouri-Kansas City (UMKC) Medical School - Children's Mercy Hospitals & Clinics (CMHC)Recruiting
  • St. Louis Children's HospitalRecruiting
  • Washington University School of MedicineRecruiting
  • Vanderbilt University Medical Center (VUMC)Recruiting
  • Cook Children's Medical CenterRecruiting
  • Baylor College of Medicine
  • Hospital de Clinicas de Porto Alegre (HCPA)
  • Children's Hospital at London Health Sciences Centre
  • Childrens Hospital Of Eastern Ontario Research Institute, University Of Ottawa
  • Institut ImagineRecruiting
  • Universitätsklinikum Köln (University of Cologne) - Children's hospital University
  • Azienda Ospedaliera Universitaria Policlinico Umberto I
  • Universitair Medisch Centrum Utrecht (UMCU) - Wilhelmina Kinderziekenhuis
  • Uniwersytet Medyczny w Lodzi - Klinika Endokrynologii i Chorob MetabolicznychRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Intravenous Bisphosphonates (IV-BP) -> Setrusumab

Setrusumab

Arm Description

Participants on IV-BP will continue their existing dose/regimen per investigator discretion; for participants not on IV-BP, the dose/regimen will be determined by the investigator. After the active-controlled period, participants will receive Setrusumab during the extension period

Participants will receive Setrusumab during the active-controlled and extension period

Outcomes

Primary Outcome Measures

Annualized Rate of all Radiographically-confirmed Fractures, Including Morphometric Vertebral Fractures During the Active-controlled Period

Secondary Outcome Measures

Annualized Rate of all Radiographically-confirmed Fractures, Excluding Morphometric Vertebral Fractures During the Active-controlled Period
Change from Baseline in Pediatric Orthopedic Society of North America Pediatric Outcomes Data Collection Instrument (POSNA-PODCI) Sports/Physical Functioning and Pain/Comfort Subscale Scores at Month 12 of the Active-controlled Period
Serum Setrusumab Concentration
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
Number of Participants With Anti-setrusumab Binding and Neutralizing Antibodies

Full Information

First Posted
March 3, 2023
Last Updated
October 20, 2023
Sponsor
Ultragenyx Pharmaceutical Inc
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1. Study Identification

Unique Protocol Identification Number
NCT05768854
Brief Title
Setrusumab vs Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta
Acronym
Cosmic
Official Title
An Open-label, Randomized, Active-Controlled, Phase 3 Study of Setrusumab Compared With Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta Types I, III or IV
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 14, 2023 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
June 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ultragenyx Pharmaceutical Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objective of the study is to evaluate the effect of setrusumab vs intravenous bisphosphonates (IV-BP) on reduction in fracture rate, including morphometric vertebral fractures in pediatric participants.
Detailed Description
Participants will be randomized 1:1 to receive either setrusumab or IV-BP. Following randomization, participants will receive setrusumab or IV-BP for up to 24 months during the Active-controlled Period. At the end of the Active-controlled Period all participants will enter the Extension Period and participants assigned to IV-BP will transition to setrusumab. During the Extension Period, all participants will receive setrusumab for a minimum of 12 months or until setrusumab becomes commercially available in their respective country or the study is discontinued. The use of any bisphosphonate is prohibited throughout the Extension Period.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteogenesis Imperfecta

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
66 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intravenous Bisphosphonates (IV-BP) -> Setrusumab
Arm Type
Active Comparator
Arm Description
Participants on IV-BP will continue their existing dose/regimen per investigator discretion; for participants not on IV-BP, the dose/regimen will be determined by the investigator. After the active-controlled period, participants will receive Setrusumab during the extension period
Arm Title
Setrusumab
Arm Type
Experimental
Arm Description
Participants will receive Setrusumab during the active-controlled and extension period
Intervention Type
Drug
Intervention Name(s)
Bisphosphonate
Intervention Description
Administered per investigator discretion via intravenous (IV) infusion
Intervention Type
Biological
Intervention Name(s)
Setrusumab
Other Intervention Name(s)
BPS804, UX143
Intervention Description
A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion
Primary Outcome Measure Information:
Title
Annualized Rate of all Radiographically-confirmed Fractures, Including Morphometric Vertebral Fractures During the Active-controlled Period
Time Frame
Up to 24 Months
Secondary Outcome Measure Information:
Title
Annualized Rate of all Radiographically-confirmed Fractures, Excluding Morphometric Vertebral Fractures During the Active-controlled Period
Time Frame
Up to 24 Months
Title
Change from Baseline in Pediatric Orthopedic Society of North America Pediatric Outcomes Data Collection Instrument (POSNA-PODCI) Sports/Physical Functioning and Pain/Comfort Subscale Scores at Month 12 of the Active-controlled Period
Time Frame
Baseline, Up to 12 Months
Title
Serum Setrusumab Concentration
Time Frame
Up to 24 Months
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
Time Frame
Up to 24 Months
Title
Number of Participants With Anti-setrusumab Binding and Neutralizing Antibodies
Time Frame
Up to 24 Months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female 2 to < 7 years of age at time of informed consent Clinical diagnosis of OI Types I, III, or IV confirmed by identification of genetic mutation in COL1A1 or COL1A2 History of ≥ 1 fracture in the past 12 months, ≥ 2 fractures in the past 24 months, or ≥ 1 femur, tibia, or humerus fracture in the past 24 months Any prior exposure to, or currently receiving, IV-bisphosphonate therapy for treatment of OI Serum 25-hydroxyvitamin D level ≥ 20 ng/mL at the Screening visit. If 25-hydroxyvitamin D levels are below 20 ng/mL, the subject may be rescreened after a minimum of 14 days of vitamin D supplementation as directed by the Investigator Exclusion Criteria: Contraindication for the use of IV bisphosphonates based on clinical judgment of the Investigator History of skeletal malignancies or bone metastases at any time History of neural foraminal stenosis (except if due to scoliosis) Clinical manifestations of Chiari malformation or basilar invagination. Presence of any other neurologic disease that has been clinically unstable within past 2 years requires review by the Medical Monitor. History of or current uncontrolled concomitant diseases that may impact bone metabolism, such as hypo/hyperparathyroidism, abnormal thyroid function, nephrotic syndrome, or Stage IV/V renal disease Any skeletal condition (other than OI) leading to bone deformity and/or increased risk of fractures, such as rickets, osteopetrosis, idiopathic juvenile osteoporosis, or skeletal dysplasia History of known cardiovascular disease such as coronary artery anomaly, Kawasaki disease, myocarditis, cardiomyopathy, myocardial infarction, stroke, or thromboembolic disease. Individuals with other congenital or acquired cardiovascular disease necessitating echocardiogram require Medical Monitor review. Investigators should consider whether the potential benefits of treatment outweigh the potential risks in patients with cardiovascular risk factors such as confirmed arterial hypertension. Hypocalcemia, defined as serum calcium levels below the age-adjusted normal limit reference ranges after a recommended ≥ 4 hour fast, at Screening Estimated glomerular filtration rate <=35 mL/min/1.73 m2 at Screening Prior treatment with growth hormone, denosumab, anti-sclerostin antibody, or other anabolic or anti-resorptive medications impacting the bone (other than bisphosphonates) at any time History of external radiation therapy Known hypersensitivity to setrusumab or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects Presence or history of any condition that, in the view of the Investigator, would interfere with participation, pose undue risk, or would confound interpretation of results Use of any investigational product or investigational medical device within 4 weeks or 5 half-lives (whichever is longer) of investigational drug prior to Screening, or during the study (per discretion of the Investigator in consultation with the Medical Monitor) Concurrent participation in another clinical study without prior approval from the study Medical Monitor
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Patients Contact: Trial Recruitment
Phone
18887568657
Email
trialrecruitment@ultragenyx.com
First Name & Middle Initial & Last Name or Official Title & Degree
HCPs Contact: Medical Information
Phone
18887568657
Email
medinfo@ultragenyx.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Ultragenyx Pharmaceutical Inc
Official's Role
Study Director
Facility Information:
Facility Name
Phoenix Children's Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85206
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Childrens Hospital LA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Name
Yale New Haven Hospital
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Individual Site Status
Recruiting
Facility Name
Nemours/ Alfred i. duPoint Hospital for Children
City
Wilmington
State/Province
Delaware
ZIP/Postal Code
19803
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's National Hospital DC
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Name
Shriners Hospitals for Children Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60707
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Missouri-Kansas City (UMKC) Medical School - Children's Mercy Hospitals & Clinics (CMHC)
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Individual Site Status
Recruiting
Facility Name
St. Louis Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Name
Vanderbilt University Medical Center (VUMC)
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
Individual Site Status
Recruiting
Facility Name
Cook Children's Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Individual Site Status
Recruiting
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Hospital de Clinicas de Porto Alegre (HCPA)
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90035-903
Country
Brazil
Individual Site Status
Not yet recruiting
Facility Name
Children's Hospital at London Health Sciences Centre
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5W9
Country
Canada
Individual Site Status
Not yet recruiting
Facility Name
Childrens Hospital Of Eastern Ontario Research Institute, University Of Ottawa
City
Ottawa
ZIP/Postal Code
KIH 8L1
Country
Canada
Individual Site Status
Not yet recruiting
Facility Name
Institut Imagine
City
Paris
ZIP/Postal Code
75015
Country
France
Individual Site Status
Recruiting
Facility Name
Universitätsklinikum Köln (University of Cologne) - Children's hospital University
City
Köln
ZIP/Postal Code
50937
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Azienda Ospedaliera Universitaria Policlinico Umberto I
City
Roma
ZIP/Postal Code
00161
Country
Italy
Individual Site Status
Not yet recruiting
Facility Name
Universitair Medisch Centrum Utrecht (UMCU) - Wilhelmina Kinderziekenhuis
City
Utrecht
ZIP/Postal Code
3584 EA
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Name
Uniwersytet Medyczny w Lodzi - Klinika Endokrynologii i Chorob Metabolicznych
City
Łódź
ZIP/Postal Code
91-738
Country
Poland
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Setrusumab vs Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta

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