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A Clinical Trial to Evaluate Safety of Vosoritide in At-risk Infants With Achondroplasia

Primary Purpose

Achondroplasia

Status

Active

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

vosoritide

About this trial

This is an interventional treatment trial for Achondroplasia focused on measuring Dwarfism, Bone Diseases, Bone Diseases, Developmental ACH, Natriuretic Peptide, C-Type, Musculoskeletal Diseases

Eligibility Criteria

0 Months - 12 Months (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Parent(s) or guardian(s) willing and able to provide signed informed consent after the nature of the study has been explained and prior to performance of any research related procedure.
Have ACH, documented by genetic testing.
Are willing and able to perform all study procedures as physically possible.
Age 0 to ≤ 12 months, at study entry (Day 1). Given that any potential impact of vosoritide therapy on the foramen magnum is dependent on treating as early as possible and as long as possible while the synchondroses at the base of the skull are still open. For subjects > 6 months of age at enrollment, a discussion between the investigator and the Medical Monitor should occur with the goal of limiting the number of subjects in the range of > 6 months to ≤ 12 months of age.
Parent(s) or caregiver(s) are willing to administer daily injections to the subject and complete the required training.
Have evidence of CMC that "may" require surgical intervention

Exclusion Criteria:

Have hypochondroplasia or short-stature condition other than achondroplasia (eg, trisomy 21, pseudoachondroplasia, etc).
Have CMC that either does not require surgical intervention (for example foramen magnum narrowing with preservation of the cerebrospinal fluid space) or does require immediate surgical intervention .
Have any of the following: Untreated congenital hypothyroidism or maternal history of hyperthyroidism, Insulin-requiring neonatal diabetes mellitus, Autoimmune inflammatory disease, Inflammatory bowel disease, Autonomic neuropathy.
Have a history of any of the following:Renal insufficiency, Chronic anemia,Baseline systolic blood pressure below age and gender specified normal range or recurrent symptomatic hypotension (defined as episodes of low blood pressure generally accompanied by symptoms eg, pallor, cyanosis, irritability, poor feeding) and Cardiac or vascular disease.
Have a clinically significant finding or arrhythmia that indicates abnormal cardiac function or conduction or QTc-F ≥ 450 msec on screening ECG.
Have been treated with growth hormone, insulin-like growth factor 1, or anabolic steroids in the 6 months prior to Screening, or long-term treatment (> 3 months) at any time.
Have ever had prior cervicomedullary decompression surgery.
Have had a fracture of the long bones or spine within 6 months prior to Screening.

Sites / Locations

Murdoch Children's Research Institute
Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital
Sheffield Children's NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Vosoritide + Standard of Care

Standard of Care Alone

Arm Description

Standard of Care treatment for cervicomedullary compression and once daily subcutaneous injection of recommended dose of vosoritide based on weight-band dosing.

Institutional standard of care monitoring and treatment for cervicomedullary compression

Outcomes

Primary Outcome Measures

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Secondary Outcome Measures

Evaluate the effect of Vosoritide on total foramen magnum volume (in cm3) by MRI volumetric measurement software

Full Information

NCT ID

NCT04554940

First Posted

September 14, 2020

Last Updated

August 1, 2023

Sponsor

BioMarin Pharmaceutical

1. Study Identification

Unique Protocol Identification Number

NCT04554940

Brief Title

A Clinical Trial to Evaluate Safety of Vosoritide in At-risk Infants With Achondroplasia

Official Title

A Randomized, Controlled, Open-label Clinical Trial With an Open-label Extension to Investigate the Safety of Vosoritide in Infants and Young Children With Achondroplasia at Risk of Requiring Cervicomedullary Decompression Surgery

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

October 10, 2020 (Actual)

Primary Completion Date

December 2027 (Anticipated)

Study Completion Date

December 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

BioMarin Pharmaceutical

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

5. Study Description

Brief Summary

Study 111-209 is a Phase 2 randomized, open-label clinical trial of BMN 111 in infants and young children with a diagnosis of Achondroplasia at a heightened risk of requiring cervicomedullary decompression surgery

6. Conditions and Keywords

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

Achondroplasia

Keywords

Dwarfism, Bone Diseases, Bone Diseases, Developmental ACH, Natriuretic Peptide, C-Type, Musculoskeletal Diseases

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Vosoritide + Standard of Care

Arm Type

Experimental

Arm Description

Standard of Care treatment for cervicomedullary compression and once daily subcutaneous injection of recommended dose of vosoritide based on weight-band dosing.

Arm Title

Standard of Care Alone

Arm Type

No Intervention

Arm Description

Institutional standard of care monitoring and treatment for cervicomedullary compression

Intervention Type

Biological

Intervention Name(s)

vosoritide

Intervention Description

Subcutaneous injection of recommended dose of BMN 111 based on weight-band dosing once daily.

Primary Outcome Measure Information:

Title

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Time Frame

Through Week 260

Secondary Outcome Measure Information:

Title

Evaluate the effect of Vosoritide on total foramen magnum volume (in cm3) by MRI volumetric measurement software

Time Frame

Through Week 260

10. Eligibility

Sex

All

Minimum Age & Unit of Time

0 Months

Maximum Age & Unit of Time

12 Months

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Parent(s) or guardian(s) willing and able to provide signed informed consent after the nature of the study has been explained and prior to performance of any research related procedure. Have ACH, documented by genetic testing. Are willing and able to perform all study procedures as physically possible. Age 0 to ≤ 12 months, at study entry (Day 1). Given that any potential impact of vosoritide therapy on the foramen magnum is dependent on treating as early as possible and as long as possible while the synchondroses at the base of the skull are still open. For subjects > 6 months of age at enrollment, a discussion between the investigator and the Medical Monitor should occur with the goal of limiting the number of subjects in the range of > 6 months to ≤ 12 months of age. Parent(s) or caregiver(s) are willing to administer daily injections to the subject and complete the required training. Have evidence of CMC that "may" require surgical intervention Exclusion Criteria: Have hypochondroplasia or short-stature condition other than achondroplasia (eg, trisomy 21, pseudoachondroplasia, etc). Have CMC that either does not require surgical intervention (for example foramen magnum narrowing with preservation of the cerebrospinal fluid space) or does require immediate surgical intervention . Have any of the following: Untreated congenital hypothyroidism or maternal history of hyperthyroidism, Insulin-requiring neonatal diabetes mellitus, Autoimmune inflammatory disease, Inflammatory bowel disease, Autonomic neuropathy. Have a history of any of the following:Renal insufficiency, Chronic anemia,Baseline systolic blood pressure below age and gender specified normal range or recurrent symptomatic hypotension (defined as episodes of low blood pressure generally accompanied by symptoms eg, pallor, cyanosis, irritability, poor feeding) and Cardiac or vascular disease. Have a clinically significant finding or arrhythmia that indicates abnormal cardiac function or conduction or QTc-F ≥ 450 msec on screening ECG. Have been treated with growth hormone, insulin-like growth factor 1, or anabolic steroids in the 6 months prior to Screening, or long-term treatment (> 3 months) at any time. Have ever had prior cervicomedullary decompression surgery. Have had a fracture of the long bones or spine within 6 months prior to Screening.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director, MD

Organizational Affiliation

BioMarin Pharmaceutical

Official's Role

Study Director

Facility Information:

Facility Name

Murdoch Children's Research Institute

City

Parkville

State/Province

Victoria

ZIP/Postal Code

3052

Country

Australia

Facility Name

Guy's and St. Thomas NHS Foundation Trust Evelina Children's Hospital

City

London

ZIP/Postal Code

SE1 7EH

Country

United Kingdom

Facility Name

Sheffield Children's NHS Foundation Trust

City

Sheffield

ZIP/Postal Code

S10 2TH

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

33761804

Citation

Savarirayan R, Irving M, Maixner W, Thompson D, Offiah AC, Connolly DJ, Raghavan A, Powell J, Kronhardt M, Jeha G, Ghani S, Fisheleva E, Day JR. Rationale, design, and methods of a randomized, controlled, open-label clinical trial with open-label extension to investigate the safety of vosoritide in infants, and young children with achondroplasia at risk of requiring cervicomedullary decompression surgery. Sci Prog. 2021 Jan-Mar;104(1):368504211003782. doi: 10.1177/00368504211003782.

Results Reference

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A Clinical Trial to Evaluate Safety of Vosoritide in At-risk Infants With Achondroplasia

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