A Study of Vosoritide Versus Placebo in Children With Hypochondroplasia Aged 0 to < 36 Months

Official title

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Vosoritide in Infants and Young Children With Hypochondroplasia, Aged 0 to < 36 Months

Overview

The purpose of this study is to evaluate the safety and efficacy of daily administration of vosoritide in participants with HCH aged 0 to \< 36 months over a 52-week period.

Detailed description

Study 111-212 is a Phase 2, randomized, double-blind, placebo-controlled, multicenter study to assess the safety and efficacy of vosoritide versus placebo in infants and young children with HCH.

Eligible participants with documented HCH confirmed by genetic testing will be randomized in a 1:1 ratio to receive vosoritide or placebo. Participants will receive study treatment daily for 52 weeks by subcutaneous (SC) injection, followed by a 2-week safety follow-up visit. Vosoritide dosing will follow a weight-band regimen.

Interventions

• Drug Vosoritide
  The vosoritide dose administered will be based on the participant's weight and will follow the weight-band dosing regimen approved for ACH
• Drug Placebo
  Subcutaneous injection of recommended dose of placebo

Primary outcome measures

• Incidence of treatment-emergent adverse events [Time frame: From baseline to end of treatment at 52 weeks]
• Incidence of serious adverse events versus placebo over the course of the study [Time frame: From baseline to end of treatment at 52 weeks]
• Changes from baseline in standard clinical laboratory values (hematology, urinalysis, and chemistry) [Time frame: At week 26, at week 52]
• Changes from baseline in heart rate [Time frame: At week 13, at week 26, at week 39, at week 52]
• Change from baseline in height Z-score [Time frame: At week 52]
• Changes from baseline in respiratory rate [Time frame: At week 13, at week 26, at week 39, at week 52]
• Changes from baseline in temperature [Time frame: At week 13, at week 26, at week 39, at week 52]
• Changes from baseline in blood pressure [Time frame: At week 13, at week 26, at week 39, at week 52]

Secondary outcome measures (12)

• Change in height [Time frame: At week 52]
• Cumulative annualized growth velocity (AGV) [Time frame: At week 52]
• 6-month interval AGV [Time frame: At week 26, at week 52]
• Change from baseline in upper to lower body segment ratio [Time frame: At week 52]
• Change from baseline in arm span [Time frame: At week 52]
• Change from baseline in total body (less head) bone mineral density (BMD) Z-score [Time frame: At week 52]
• Change from baseline in lumbar spine BMD Z-score [Time frame: At week 52]
• Change from baseline in total body (less head) bone mineral content (BMC) as measured by DXA [Time frame: At week 52]
• Change from baseline in lumbar spine BMC as measured by DXA [Time frame: At week 52]
• Area under the plasma vosoritide concentration time-curve from time 0 to infinity (AUC0-∞) [Time frame: At week 26, at week 52]
• Area under the plasma vosoritide concentration time-curve from time 0 to the last measurable concentration (AUC0-t) [Time frame: At week 26, at week 52]
• Elimination half-life of vosoritide (t½) [Time frame: At week 26, at week 52]

Eligibility criteria

Inclusion criteria

• Participants must be 0 to < 36 months of age at randomization.
• Participants must have a confirmed genetic diagnosis of HCH (obtained via whole genome sequencing; presence of a FGFR3 pathogenic variant associated with HCH).
• Participants aged 0 to < 12 months must have a height Z-score of ≤ -1.0 SDS andparticipants aged ≥ 12 to < 36 months must have a height Z-score of ≤ -2.0 SDS in reference to the average stature of the same sex and age, as calculated using the Center for Disease Control and Prevention (CDC) growth charts.
• Participant's weight at the Day 1 visit (pre-treatment) must be ≥ 3 kg.

Exclusion criteria

• Short stature condition other than HCH (eg, ACH, trisomy 21, pseudoachondroplasia).
• Have an unstable medical condition likely to require surgical intervention during the study period.
• Taking any of the prohibited medications.
• Have been treated with growth hormone, insulin-like growth factor 1 (IGF-1), or anabolic steroids in the 6 months prior to Screening, or long-term treatment (> 3 months) at any time.
• Require any investigational agent prior to completion of study period.
• Have received another investigational product or investigational medical device within 30 days prior to the Screening visit.
• Have used any other investigational product or investigational medical device for the treatment of HCH or short stature at any time.
• Have current malignancy, history of malignancy, or currently under work-up for suspected malignancy.
• Have known hypersensitivity to vosoritide or its excipients.
• Have a condition or circumstance that, in the view of the investigator, places the participant at high risk for poor treatment compliance or for not completing the study.
• Have any concurrent disease or condition that, in the view of the investigator, will interfere with study participation or safety evaluations, for any reason.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 10 centers

• Phoenix Children's Hospital - Thomas Campus (Main) — Phoenix
• Cedars-Sinai Medical Center — Los Angeles
• Benioff Children's Hospital - Oakland — Oakland
• Children's National Medical Center — Washington D.C.
• Ann & Robert H. Lurie Children's Hospital of Chicago — Chicago
• The Johns Hopkins University School of Medicine — Baltimore
• University of Minneasota Masonic Children's Hospital — Minneapolis
• University of Missouri — Columbia
• … and 2 more centers

Japan · 5 centers

• Kumamoto University Hospital — Kumamoto
• Osaka Women's and Children's Hospital — Osaka
• Institute of Science Tokyo Hospital — Tokyo
• Nihon University Itabashi Hospital — Tokyo
• Tottori University Hospital — Tottori

Germany · 3 centers

• Uniklinik Köln — Cologne
• Universitätsklinikum des Saarlandes — Homburg
• Universitätskinderklinik Magdeburg — Magdeburg

Australia · 2 centers

• Children's Health Queensland Hospital and Health Service — South Brisbane
• Royal Children's Hospital Melbourne — Parkville

France · 2 centers

• Hôpital Bicêtre — Le Kremlin-Bicêtre
• Hospices Civils de Lyon - Hôpital Femme Mère Enfant — Bron

Italy · 2 centers

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Roma
• IRCCS Istituto Giannina Gaslini — Genova

United Kingdom · 2 centers

• Myriad Trials — London
• Great Ormond Street Hospital — London

Identifiers

NCT: NCT07126262 · 111-212

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗