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An Extension Study to Evaluate Safety and Efficacy of BMN 111 in Children With Achondroplasia

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ClinicalTrials.gov Identifier: NCT03989947
Recruitment Status : Enrolling by invitation
First Posted : June 18, 2019
Last Update Posted : July 26, 2019
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Brief Summary:
This is a Phase 2, open-label multi-center long-term extension study, with approximately 70 subjects, to evaluate the safety and efficacy of BMN111 in children with Achondroplasia until subjects reach near-adult final height. Eligible subjects will have completed 1 year of BMN111 or placebo treatment in the 111-206 study and once enrolled in the 111-208 extension study will receive a daily dose of BMN111 by subcutaneous injection according to their age as determined by 111-206.

Condition or disease Intervention/treatment Phase
Achondroplasia Drug: Active BMN 111: Daily subcutaneous injection of 15 ug/kg of BMN 111 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Open-Label Long-Term Extension Study to Evaluate the Safety and Efficacy of BMN 111 in Children With Achondroplasia
Actual Study Start Date : June 12, 2019
Estimated Primary Completion Date : September 2026
Estimated Study Completion Date : December 2026


Arm Intervention/treatment
Experimental: Active BMN 111
Age-appropriate daily subcutaneous injections of BMN 111 as determined by the 111-206 study
Drug: Active BMN 111: Daily subcutaneous injection of 15 ug/kg of BMN 111
Modified recombinant human C-type natriuretic peptide
Other Name: Vosoritide




Primary Outcome Measures :
  1. Evaluate the incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: "Through study completion, an average of 5 years" ]
    Number of study participants with treatment-emergent adverse events or serious adverse events

  2. Evaluate change in height/length z-score in children with ACH treated with BMN 111 [ Time Frame: "Through study completion, an average of 5 years" ]

Secondary Outcome Measures :
  1. Evaluate the change from baseline of mean annualized growth velocity (AGV) [ Time Frame: "Through study completion, an average of 5 years" ]
  2. Characterize maximum concentration (Cmax) of BMN 111 in plasma [ Time Frame: "Through study completion, an average of 5 years" ]
  3. Characterize the area under the plasma concentration time-curve from time 0 to infinity (AUC0-∞) [ Time Frame: "Through study completion, an average of 5 years" ]
  4. Characterize the elimination half-life of BMN 111 (t½) [ Time Frame: "Through study completion, an average of 5 years" ]
  5. Characterize the apparent clearance of drug [ Time Frame: "Through study completion, an average of 5 years" ]
  6. Characterize the apparent volume of distribution based upon the terminal phase (Vz/F) [ Time Frame: "Through study completion, an average of 5 years" ]
  7. Characterize the amount of time BMN 111 is present at maximum concentration (Tmax) [ Time Frame: "Through study completion, an average of 5 years" ]
  8. Evaluate the change from baseline on body proportion ratios of the extremities [ Time Frame: "Through study completion, an average of 5 years" ]
  9. Effect of BMN 111 on bone morphology and quality by XRay [ Time Frame: "Through study completion, an average of 5 years" ]
  10. The effect of BMN 111 on bone morphology/quality will be assessed by measuring bone mineral density via Dual X-ray Absorptiometry [ Time Frame: "Through study completion, an average of 5 years" ]
  11. Potential Changes in health-related quality of life as measured by the quality of life in Short- statured youth [ Time Frame: "Through study completion, an average of 5 years" ]
    Evaluate the long-term effect of BMN 111 on health-related quality of life, developmental status and functional independence, using age-specific QoL and functional independence questionnaires (Bayley-III, WeeFIM, ITQOL, QoLISSY, PedsQL, Child Behavior Checklist 1.5-5 [CBCL 1.5-5], Child Behavior Checklist 6-18 [CBCL 6-18]).

  12. BMN 111 activity will be assessed by measuring bone and collagen metabolism [ Time Frame: "Through study completion, an average of 5 years" ]
  13. Describe the incidence of surgical and medical interventions related to achondroplasia [ Time Frame: "Through study completion, an average of 5 years" ]
  14. Assess effect on sleep disordered breathing by polysomnography in patients up to 5 years old. [ Time Frame: "Through study completion, an average of 1 year" ]
  15. Evaluate the effect of BMN 111 on skull and brain morphology, including foramen magnum, ventricular and brain parenchymal dimensions by MRI in patients up to 3 years old. [ Time Frame: "Through study completion, an average of 1 year" ]


Information from the National Library of Medicine

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Ages Eligible for Study:   15 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Must have completed Study 111-206 on investigational treatment (BMN 111 or placebo).
  2. Parent(s) or guardian(s) are willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to performance of any research related procedure. Also, subjects under the age of majority are willing and able to provide written assent (if required by local regulations or the IRB/IEC) after the nature of the study has been explained and prior to performance of any research-related procedure. Subjects who reach the age of majority in their country while the study is ongoing will be asked to provide their own written consent again upon reaching the legal age of majority.
  3. Are willing and able to perform all study procedures

Exclusion Criteria:

  1. Permanently discontinued BMN 111 or placebo prior to completion of Study 111-206
  2. Have a clinically significant finding or arrhythmia on ECG that indicates abnormal cardiac function or conduction or QTc-F > 450 msec
  3. Require any investigational agent (except BMN 111) prior to completion of study period
  4. Current therapy with antihypertensive medications, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, diuretics, beta-blockers, calcium-channel blockers, cardiac glycosides, systemic anticholinergic agents, GnRH agonists, any medication that may impair or enhance compensatory tachycardia, diuretics, or other drugs known to alter renal or tubular function
  5. Pregnant or planning to become pregnant (self or partner) at any time during the study
  6. Concurrent disease or condition that, in the view of the investigator, would interfere with study participation or safety evaluations, for any reason
  7. Have a condition or circumstance that, in the view of the investigator, places the subject at high risk for poor treatment compliance

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03989947


Locations
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United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-2578
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
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Study Director: Medical Director MD BioMarin Pharmaceutical

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Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT03989947     History of Changes
Other Study ID Numbers: 111-208
First Posted: June 18, 2019    Key Record Dates
Last Update Posted: July 26, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BioMarin Pharmaceutical:
Dwarfism
Bone Disease
ACH
Natriuretic Peptide C-Type
Musculoskeletal Diseases
Skeletal Dysplasias
Additional relevant MeSH terms:
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Achondroplasia
Dwarfism
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Osteochondrodysplasias
Genetic Diseases, Inborn
Natriuretic Peptide, C-Type
Natriuretic Agents
Physiological Effects of Drugs