A Phase 2 Study of BMN 111 to Evaluate Safety, Tolerability, and Efficacy in Children With Achondroplasia

NCT02055157 | Completed Phase 2 Results DMC

• 2 other identifiers: 111-2022013-004137-32
• Study Type: interventional
• Target: 35
• Locations: 4 countries
• Sites: 9

Brief Summary

This is a Phase 2, open-label, sequential cohort dose-escalation study of BMN 111 in children with achondroplasia. The primary objective is to assess the safety and tolerability of daily BMN 111 administered to children with achondroplasia.

Conditions

Achondroplasia

Keywords

Achondroplasia; Dwarfism; Bone Diseases, Developmental; Bone Diseases

Outcome Measures

Primary Outcomes (2)

• Overall Summary of Adverse Events During Initial 6-Month Period

  A treatment-emergent Adverse Events (TEAE) is any Adverse Events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration. Serious adverse event (SAE).

  Up to Month 6 ± 7 Days

• Overall Summary of Adverse Events During Entire Study Period

  A treatment-emergent Adverse Events (TEAE) is any Adverse Events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration. TEAE - Treatment-emergent adverse event. SAE - Serious adverse event.

  Up to Month 25 ± 7 Days

Secondary Outcomes (21)

• Change From Baseline in Annualized Growth Velocity (AGV) During Initial 6-Month

  At 6 month (Day 183)

• Change From Baseline in Annualized Growth Velocity (AGV) During Entire Study Period - Cohort 3 and 4

  At month 24

• Change From Baseline in Annualized Growth Velocity (AGV) During Entire Study Period - Cohort 1 and 2 Switchers

  At month 24

• Change From Baseline in Height Z-Scores Using Centers for Disease Control and Prevention (CDC) Reference Standard During Initial 6-Months

  At month 6 (Day 183)

• Change From Baseline in Height Z-Scores Using CDC Reference Standard During Entire Study Period - Cohort 3 and 4

  At month 24

Study Arms (4)

Cohort 1

EXPERIMENTAL

Cohort 1: 2.5 ug/kg

Drug: BMN 111

Cohort 2

EXPERIMENTAL

Cohort 2: 7.5 ug/kg,

Drug: BMN 111

Cohort 3

EXPERIMENTAL

Cohort 3: 15 ug/Kg

Drug: BMN 111

Cohort 4

EXPERIMENTAL

Cohort 4: 30 ug/kg

Drug: BMN 111

Interventions

BMN 111 DRUG

BMN 111 will be administered daily for 24 months in an open-label sequential dose adjustment fashion.

Also known as: Modified recombinant human C-type natriuretic peptide, Vosoritide

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 5 Years - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Parent(s) or guardian(s) are willing and able to provide written, signed informed consent
• to 14 years old at end of study
• ACH, documented by clinical grounds, confirmed by genetic testing
• At least 6-month of pretreatment growth assessment in Study 111-901 before study entry, and one standing height at least 6 months prior to screening for 111-202
• Negative pregnancy test at the Screening Visit for females ≥ 10 years old or who have begun menses
• If sexually active, willing to use a highly effective method of contraception while participating in the study
• Ambulatory, able to stand without assistance
• Willing and able to perform all study procedures as physically possible
• Parents/caregivers willing to administer daily injections to the subjects
• Appropriate written informed consent

You may not qualify if:

• Hypochondroplasia or short stature condition other than ACH
• Have any of the following:
• Hypothyroidism or hyperthyroidism
• Insulin-requiring diabetes mellitus
• Autoimmune inflammatory disease
• Inflammatory bowel disease
• Autonomic neuropathy
• Recent acute illness associated with volume dehydration not completely resolved prior to the first dose of study drug
• Unstable condition requiring surgical intervention during the study
• Growth plates have fused
• Have a history of any of the following:
• Renal insufficiency, defined as creatinine \> 2 mg/dl
• Anemia
• Baseline systolic BP \< 75 mm Hg or recurrent symptomatic hypotension or recurrent symptomatic hypotension, recurrent symptomatic orthostatic hypotension
• Cardiac or vascular disease, including the following:

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (9)

Children's Hospital & Research Center Oakland

Oakland, California, 94609, United States

Location

Harbor - UCLA Medical Center

Torrance, California, 90509, United States

Location

Ann and Robert H. Lurie Childrens Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Johns Hopkins McKusick - Institute of Genetic Medicine

Baltimore, Maryland, 21287, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232-2578, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Murdoch Children's Research Institute

Parkville, Victoria, 3052, Australia

Location

Institut Necker

Paris, 75015, France

Location

Guys & St. Thomas NHS Foundation Trust Evelina Hospital

London, SE1 9RT, United Kingdom

Location

Related Publications (3)

• Qi Y, Chan ML, Mould DR, Larimore K, Fisheleva E, Cherukuri A, Day J, Savarirayan R, Irving M, Bacino CA, Hoover-Fong J, Ozono K, Mohnike K, Wilcox WR, Bober MB, Henshaw J. Development of a Weight-Band Dosing Approach for Vosoritide in Children with Achondroplasia Using a Population Pharmacokinetic Model. Clin Pharmacokinet. 2024 May;63(5):707-719. doi: 10.1007/s40262-024-01371-6. Epub 2024 Apr 23.

  PMID: 38649657 DERIVED

• Chan ML, Qi Y, Larimore K, Cherukuri A, Seid L, Jayaram K, Jeha G, Fisheleva E, Day J, Huntsman-Labed A, Savarirayan R, Irving M, Bacino CA, Hoover-Fong J, Ozono K, Mohnike K, Wilcox WR, Horton WA, Henshaw J. Pharmacokinetics and Exposure-Response of Vosoritide in Children with Achondroplasia. Clin Pharmacokinet. 2022 Feb;61(2):263-280. doi: 10.1007/s40262-021-01059-1. Epub 2021 Aug 25.

  PMID: 34431071 DERIVED

• Savarirayan R, Irving M, Bacino CA, Bostwick B, Charrow J, Cormier-Daire V, Le Quan Sang KH, Dickson P, Harmatz P, Phillips J, Owen N, Cherukuri A, Jayaram K, Jeha GS, Larimore K, Chan ML, Huntsman Labed A, Day J, Hoover-Fong J. C-Type Natriuretic Peptide Analogue Therapy in Children with Achondroplasia. N Engl J Med. 2019 Jul 4;381(1):25-35. doi: 10.1056/NEJMoa1813446. Epub 2019 Jun 18.

  PMID: 31269546 DERIVED

MeSH Terms

Conditions

Achondroplasia; Dwarfism; Bone Diseases, Developmental; Bone Diseases

Interventions

vosoritide

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases; Osteochondrodysplasias; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases

Results Point of Contact

• Title: Alice Hunstman-Labed
• Organization: BioMarin Pharmaceutical Inc.

alice.huntsmanlabed@bmrn.com

+44 207 4203392

Study Officials

• Medical Director, MD

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2013
• First Posted: February 5, 2014
• Study Start: January 13, 2014
• Primary Completion: October 2, 2017
• Study Completion: October 2, 2017
• Last Updated: January 15, 2021
• Results First Posted: January 15, 2021

Record last verified: 2020-12

Locations

AU (1); GB (1); US (6); FR (1)