BMN 111 for Achondroplasia

(ACH Trial)

Not currently recruiting at 8 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: BioMarin Pharmaceutical

Must be taking: BMN 111

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, Poor compliance, Others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Until near final adult height is reached, and up to at least 16 years of age for females and 18 years of age for males

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests BMN 111, a treatment for children with achondroplasia, a genetic condition affecting bone growth and resulting in shorter stature. The main goal is to assess the long-term safety and effectiveness of BMN 111. This study includes children who have taken BMN 111 for two years in an earlier study and can continue with daily injections. Participants should have completed the initial treatment phase and be able to meet the study's requirements. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that you cannot be on chronic therapy with restricted medications. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that BMN 111 is likely to be safe for humans?

Research has shown that BMN 111 is generally safe for children with achondroplasia. In earlier studies, most side effects were mild to moderate, with common issues including injection site reactions, fever, and headache. Serious side effects were rare.

The safety of BMN 111 has been studied over extended periods, helping to ensure its long-term safety. The FDA has also reviewed data on BMN 111, supporting its safety.

This information provides an understanding of what to expect regarding safety when participating in a trial involving BMN 111. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for achondroplasia?

Unlike the standard of care for achondroplasia, which often involves surgical procedures or growth hormone therapy, BMN 111 is unique because it targets the root cause of the condition. BMN 111, also known as vosoritide, works by blocking the activity of a specific receptor that limits bone growth, specifically targeting the pathway that causes the growth impairment in achondroplasia. This innovative approach offers a non-invasive, precision treatment in the form of a subcutaneous injection, potentially improving growth outcomes for those with achondroplasia without the need for surgery or daily hormone injections. Researchers are excited about BMN 111 because it represents a targeted therapy that could significantly enhance quality of life for patients by addressing the underlying genetic cause of their condition.

What evidence suggests that BMN 111 might be an effective treatment for achondroplasia?

Research has shown that BMN 111, also known as vosoritide, may help treat achondroplasia, a common type of dwarfism. In one study, children who received BMN 111 grew faster than expected without the treatment. This medication targets a specific process in the body that affects bone growth, helping bones develop more normally. These findings suggest that BMN 111 could effectively improve growth in children with achondroplasia. ^{2 3 4 6 7}

Who Is on the Research Team?

Medical Director, MD

Principal Investigator

BioMarin Pharmaceutical

Are You a Good Fit for This Trial?

This trial is for children with Achondroplasia who have already completed 24 months of BMN 111 treatment in a previous study. They must be able to perform study procedures, use contraception if sexually active, and not be pregnant. Those reaching legal adult age during the study will need to consent again.

Inclusion Criteria

I am willing and able to follow all study requirements.

I am a female over 10 or have started my periods and can take pregnancy tests during the study.

Parent(s) or guardian(s) are willing and able to provide written, signed informed consent. Subjects under the age of majority are willing and able to provide written assent (if required). Subjects who reach the age of majority in their country will be asked to provide their own written consent upon reaching the legal age of majority

Exclusion Criteria

Concurrent disease or condition that, in the view of the Investigator, would interfere with study participation or safety evaluations for any reason

Subject is pregnant at Baseline visit or planning to become pregnant (self or partner) at any time during the study

Requires any investigational agent prior to completion of study period

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily subcutaneous injections of BMN 111

Until near final adult height is reached, and up to at least 16 years of age for females and 18 years of age for males

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue receiving BMN 111 to evaluate long-term safety and efficacy

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• BMN 111

Trial Overview The trial tests the long-term safety and effectiveness of daily injections of BMN 111 in children with Achondroplasia over an extended period after they've been treated for two years in a prior study (111-202).

How Is the Trial Designed?

Group I: BMN 111 - Subcutaneous Injection Experimental Treatment 1 Intervention

111-205 is an open-label, extension study. Subjects receive the same stable dose of BMN 111 received upon completion of the 111-202 study, initially up to 30 μg/kg. BMN 111 will be administered by weight-band dosing regimen.

Who Is Running the Clinical Trial?

BioMarin Pharmaceutical

Lead Sponsor

Trials

162

Recruited

115,000+

Alexander Hardy

BioMarin Pharmaceutical

Chief Executive Officer since 2023

MBA from INSEAD

Greg Friberg

BioMarin Pharmaceutical

Chief Medical Officer

MD from New York Medical College

Published Research Related to This Trial

Vosoritide is the first approved treatment for achondroplasia, and parents of children using it reported a strong motivation to manage the daily injectable treatment for potential long-term benefits, such as improved height and independence.

The study highlighted the need for better support and consistent training for families, as experiences with treatment initiation varied significantly, impacting their ability to manage the treatment effectively at home.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parents' Experience of Administering Vosoritide: A Daily Injectable for Children with Achondroplasia. NiMhurchadha, S., Butler, K., Argent, R., et al.[2023]

Achondroplasia, the most common form of dwarfism, is caused by a mutation in the FGFR3 gene that leads to increased inhibition of cartilage formation, resulting in characteristic phenotypic features.

Vosoritide, a modified version of C-type natriuretic peptide (CNP) with a longer half-life, has been shown in clinical trials to significantly increase growth velocity in children with achondroplasia before their growth plates fuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of vosoritide in the treatment of achondroplasia. Paton, DM.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03197766

A Study to Evaluate the Efficacy and Safety of BMN 111 in ... This is a Phase 3 randomized, placebo-controlled, double-blind multicenter study with approximately 110 subjects, aged 5 to < 18 years old.

2. medical.biomarin.com medical.biomarin.com/en-us/wp-content/uploads/sites/2/2024/03/ACMG-2024-208-Results_Approved-for-use.pdf?v=1.0

Results from a phase II extension study with vosoritide ... trial (BMN 111-202) and its extension study. (BMN 111-205) in children with ACH aged ≥ 5 years showed that vosoritide treatment resulted in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02055157

NCT02055157 | A Phase 2 Study of BMN 111 to Evaluate ... 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 ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2021/214938Orig1s000IntegratedR.pdf

214938Orig1s000 - accessdata.fda.gov Tolerability, and Efficacy of BMN-111 in Children with Achondroplasia (who completed. Study 111-202).” • On February 29, 2016, the Office of Pharmaceutical ...

5. clinicaltrials.biomarin.com clinicaltrials.biomarin.com/clinical-trial/an-extension-study-to-evaluate-safety-and-efficacy-of-bmn-111-in-children-with-achondroplasia/

An Extension Study to Evaluate Safety and Efficacy of BMN ... 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03424018

NCT03424018 | An Extension Study to Evaluate the ... The intent and design of this Phase 3 study is to assess BMN 111 as a therapeutic option for the treatment of children with Achondroplasia. Official Title.

7. catalogues.ema.europa.eu catalogues.ema.europa.eu/node/3537/administrative-details

A multicentre, non-interventional study to evaluate long-term ... This post-authorisation safety study (PASS, BMN 111-603) will evaluate the long-term safety of treatment with Voxzogo in subjects with achondroplasia (ACH) in ...