Evidence map›Paper›PMID 39012717›Full record

Trial reportJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2024

Setrusumab for the treatment of osteogenesis imperfecta: 12-month results from the phase 2b asteroid study.

Francis H Glorieux, Bente Langdahl, Roland Chapurlat, Suzanne Jan De Beur, Vernon Reid Sutton, Kenneth E S Poole, Kathryn M Dahir, Eric S Orwoll, Bettina M Willie, Nicholas Mikolajewicz and 8 more

Erratum issued Registry-linked trialAbstract readClinical Trial, Phase IIRandomized Controlled TrialMulticenter Study
In one paragraph

Trial report in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03118570 (A Phase 2b, Multicentre, Multinational, Double-blind, Dose-finding Study, Incorporating an Open Label Substudy, in Adult Patients With Type I, III or IV Osteogenesis Imperfecta Treated With Setrusumab), which is not on this map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03118570 phase2completednot on this map

A Phase 2b, Multicentre, Multinational, Double-blind, Dose-finding Study, Incorporating an Open Label Substudy, in Adult Patients With Type I, III or IV Osteogenesis Imperfecta Treated With Setrusumab (BPS804)

TypeinterventionalSponsorUltragenyx Pharmaceutical IncRan2017 to 2020Enrolled112ConditionsOsteogenesis Imperfecta, Type I, Osteogenesis Imperfecta Type III, Osteogenesis Imperfecta Type IVArmssetrusumab, Calcium, Vitamin D, zoledronic acid (optional)
3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Trial
  4. Bone reports · 2026
    Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Romosozumab in severe postmenopausal osteoporosis-real-world data from 192 women.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
    Article
  10. [Metabolic bone disorders: what the internist must not overlook].Innere Medizin (Heidelberg, Germany) · 2026
    Review
  11. Article
  12. Romosozumab does not improve volumetric bone mineral density at distal radius but is associated with early changes in bone strength: a prospective study.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
    Article
  13. Bone microstructural and strength changes over 1 year in children with osteogenesis imperfecta are comparable to age- and sex-matched healthy controls.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026
    Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Francis H GlorieuxDepartments of Surgery, Pediatrics and Human Genetics, Shriners Hospitals for Children, McGill University, Montreal, Quebec H4A 0A9, Canada.
Bente LangdahlDepartment of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Middle Jutland 8200, Denmark.
Roland ChapurlatInserm UMR 1033, Edouard Herriot Hospital, 69372 Lyon cedex 08, France.
Suzanne Jan De BeurDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
Vernon Reid SuttonDepartment of Molecular & Human Genetics, Baylor College of Medicine & Texas Children's Hospital, Houston, TX 77030, United States.
Kenneth E S PooleDepartment of Medicine & Cambridge NIHR Biomedical Research Centre, University of Cambridge, Cambridge CB3 0FA, United Kingdom.
Kathryn M DahirDivision of Endocrinology, Vanderbilt University Medical Center, Nashville, TN 37232, United States.ORCID 0000-0002-9980-9138
Eric S OrwollDivision of Endocrinology, Diabetes and Clinical Nutrition, School of Medicine, Oregon Health & Sciences University, Portland, OR 97239, United States.
Bettina M WillieFaculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal H3A 2T5, Canada.ORCID 0000-0003-2907-3580
Nicholas MikolajewiczFaculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal H3A 2T5, Canada.
Elizabeth ZimmermannFaculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal H3A 2T5, Canada.ORCID 0000-0001-9927-3372
Seyedmahdi HosseinitabatabaeiFaculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal H3A 2T5, Canada.ORCID 0000-0002-5638-976X
Michael S OminskyUltragenyx Pharmaceutical Inc., Novato, CA 94949, United States.
Chris SavilleICON Plc, Leopardstown, Dublin D 18, Ireland.
James ClancyMereo BioPharma, London W16 0QF, United Kingdom.
Alastair MacKinnonMereo BioPharma, London W16 0QF, United Kingdom.
Arun MistryMereo BioPharma, London W16 0QF, United Kingdom.
Muhammad K JavaidNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Wellington Square, Oxford OX1 2JD, United Kingdom.ORCID 0000-0001-7985-0048

Funding

Oregon Clinical and Translational Research Institute - The National COVID Cohort Collaborative (N3C)UL1TR002369 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI Cynthia D Morris, Christopher G. Slatore · 2017 to 2026
$78.4M
Cambridge NIHR Biomedical Research CentreFRQS Programme de Bourses de ChercheurMereo BioPharmaNCATS NIH HHS UL1 TR002369Ultragenyx Pharmaceutical IncUltragenyx Pharmaceutical Inc.
6 · The paper itself

Abstract

Osteogenesis imperfecta (OI) is a rare genetic disorder commonly caused by variants of the type I collagen genes COL1A1 and COL1A2. OI is associated with increased bone fragility, bone deformities, bone pain, and reduced growth. Setrusumab, a neutralizing antibody to sclerostin, increased areal bone mineral density (aBMD) in a 21-week phase 2a dose escalation study. The phase 2b Asteroid (NCT03118570) study evaluated the efficacy and safety of setrusumab in adults. Adults with a clinical diagnosis of OI type I, III, or IV, a pathogenic variant in COL1A1/A2, and a recent fragility fracture were randomized 1:1:1:1 to receive 2, 8, or 20 mg/kg setrusumab doses or placebo by monthly intravenous infusion during a 12-mo treatment period. Participants initially randomized to the placebo group were subsequently reassigned to receive setrusumab 20 mg/kg open label. Therefore, only results from the 2, 8, and 20 mg/kg double-blind groups are presented herein. The primary endpoint of Asteroid was change in distal radial trabecular volumetric bone mineral density (vBMD) from baseline at month 12, supported by changes in high-resolution peripheral quantitative computed tomography micro-finite element (microFE)-derived bone strength. A total of 110 adults were enrolled with similar baseline characteristics across treatment groups. At 12 mo, there was a significant increase in mean (SE) failure load in the 20 mg/kg group (3.17% [1.26%]) and stiffness in the 8 (3.06% [1.70%]) and 20 mg/kg (3.19% [1.29%]) groups from baseline. There were no changes in radial trabecula vBMD (p>05). Gains in failure load and stiffness were similar across OI types. There were no significant differences in annualized fracture rates between doses. Two adults in the 20 mg/kg group experienced related serious adverse reactions. Asteroid demonstrated a beneficial effect of setrusumab on estimates of bone strength across the different types of OI and provides the basis for additional phase 3 evaluation.

Indexed as

Bone DensityOsteogenesis ImperfectaAdultAgedFemaleHumansMaleMiddle AgedTreatment Outcomebone mineral densityosteogenesis imperfectarare diseasesclerostinsetrusumab

Identifiers

PMID39012717
PMCPMC11371902

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.