Study to Assess Dose, Efficacy and Safety of Setrusumab in Participants With Osteogenesis Imperfecta (ORBIT)

E
Erik Imel, MD

Primary Investigator

Administratively Closed
5 years - 25 years
All
Phase 2/3
219 participants needed
2 Locations

Brief description of study

The primary objectives of the study are to identify a setrusumab dosing strategy inwith OI and to evaluate the effect of setrusumab vs placebo on reduction inure rate.

Detailed description of study

Participants in Phase 2 will be randomized 1:1 to receive low dose or high dose setrusumab. Participants will continue receiving their assigned dose until the selected dosing strategydetermined for the remainder of the study. Phase 2 participants will receive setrusumab athe selected dosing strategy in the open-label treatment extension period. Phase 3will be randomized 2:1 to receive setrusumab or placebo. Phase 3 participants will transition to an open-label treatment extension period after the Phase 3 primaryysis is complete, or once a participant has completed 24 months of treatment in the double-blind period, whichever is sooner. Participants in the Phase 2 and Phase 3 treatmentds will receive open-label setrusumab treatment for at least 12 months, withhe ability to extend until commercial availability in their respective country.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Osteogenesis Imperfecta
  • Age: 5 years - 25 years
  • Gender: All

Inclusion Criteria:
  • Confirmed diagnosis of OI Types I, III, or IV as confirmed by identification ofgenetic mutation in collagen, type I, alpha 1 (COL1A1) or collagen, type I, alpha 2 (COLA2)
  • ≥ 1 fracture in the past 12 months, ≥ 2 fractures in the past 24 months or ≥ 1 tibia,ur or humerus fracture in the past 24 months
  • Serum 25 hydroxyvitamin D ≥ 20 ng/mL at the Screening Visit. If levels are below 20g/mL the subject may be rescreened after a minimum of 14 days of supplementation asdirected by their treating physician
  • Willing to not receive bisphosphonate therapy during the study
  • From the period following informed consent to 60 days after the last dose of the studydrug, females of childbearing potential and fertile males must consent to use highlyve contraception. If female, agree not to become pregnant. If male, agree nother a child or donate sperm
  • Willing and able to provide informed consent for subjects greater than or equal to 18years of age, or provide assent (if possible) and have a legally authorizedve provide informed consent, after the nature of the study has beend and prior to any research-related procedures
  • Willing to provide access to medical records for the collection of radiographic data,ure data, growth data, and disease history
  • Must, in the opinion of the Investigator, be willing and able to complete all aspectshe study, adhere to the study visit schedule, and comply with the assessments
Exclusion Criteria:
  • For Phase 2 Only: A history of bone surgery within the previous 6 months prior tog or planned bone surgery for the first 3 months of the study
  • History of skeletal malignancies or bone metastases at any time
  • History of neural foraminal stenosis (except if due to scoliosis)
  • Clinical manifestation s of Chiari malformation or basilar invagination. Presence ofy other neurologic disease that has been unstable within past 2 years requiresview by the Medical Monitor
  • History of or uncontrolled concomitant diseases such as hypo/hyperparathyroidism,Paget's disease, abnormal thyroid function, thyroid disease or other endocrinedisorders or conditions that could affect bone metabolism such as Stage IV/V renaldisease
  • Rickets or any skeletal condition (other than OI) leading to long-bone deformitiesd/or increased risk of fractures
  • History of stroke, myocardial infarction, transient ischemic attack or angina.
  • Hypocalcemia, defined as serum calcium levels below the age-adjusted normal limits≥ 4 hour fast
  • Estimated glomerular filtration rate ≤ 29 mL/min/1.73 m2
  • Prior treatment with the following:
    1. Bisphosphonate use prior to Screening that is a minimum of 3 months or the lengthhe dosing interval up to 6 months
    2. Teriparatide, growth hormone, or other bone anabolic or anti-resorptivedications within 6 months of Screening
    3. Denosumab within 24 months of Screening
  • Documented alcohol and/or drug abuse within 12 months prior to dosing or evidence of
    such abuse as indicated by the laboratory results during the Screening assessments
  • Presence or history of any condition that, in the view of the Investigator, wouldwith participation, pose undue risk, or would confound interpretation ofults
  • Known hypersensitivity to setrusumab or excipients that, in the judgment of thevestigator, places the subject at increased risk for adverse effects
  • History of external radiation therapy
  • Pregnant or breastfeeding or planning to become pregnant (self or partner) at any timeduring the study
  • Use of any investigational product or investigational medical device within 4 weeks or5 half-lives of investigational drug (whichever is longer) prior to Screening, orduring the study (per discretion of the Investigator in consultation with the Medical)
  • Concurrent participation in another clinical study without prior approval from thevestigator in consultation with the Medical Monitor

Updated on 29 Aug 2024. Study ID: UX143-CL301, ENDO-ULTRAGENYX-OI, 13589

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