TYRA-300 for Achondroplasia
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Tyra Biosciences, Inc
Must not be taking: Cyp3A4 inhibitors/inducers
Disqualifiers: Endocrine conditions, Limb surgery, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The purpose of this study is to evaluate the safety, tolerability, and identify potentially effective dose(s) of TYRA-300 in children with achondroplasia with open growth plates.
Will I have to stop taking my current medications?
The trial requires that participants do not take medications that strongly affect a specific liver enzyme (cytochrome P450 3A4). If your current medications do not fall into this category, you may not need to stop them.
How does the drug TYRA-300 differ from other treatments for achondroplasia?
TYRA-300 is unique because it is a tyrosine kinase inhibitor (a type of drug that blocks certain enzymes) targeting the FGFR3 gene mutation, which is the cause of achondroplasia. This approach is different from other treatments like vosoritide, which aims to increase growth velocity, as TYRA-300 directly addresses the genetic mutation responsible for the condition.
12345Eligibility Criteria
This trial is for children aged 3 to 10 with a confirmed diagnosis of achondroplasia, which is a bone growth disorder. They must have open growth plates, be able to walk and take oral medication independently. Consent from parents or guardians is required, and the child's willingness to assent if applicable.Inclusion Criteria
I am between 3 and 10 years old.
I can stand and walk on my own.
I am between 3 and 10 years old and have not had treatment to speed up growth.
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose-Escalation
Participants receive TYRA-300 in a dose-escalation format to determine safety and tolerability
12 weeks
Weight adjustments every 3 months
Dose-Expansion
Participants continue to receive TYRA-300 to identify potentially effective dose(s)
12 weeks
Weight adjustments every 3 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests different doses of TYRA-300 (0.125 mg/kg up to 0.50 mg/kg) in children with achondroplasia to assess safety, tolerability, and effective dosing for promoting bone growth.
4Treatment groups
Experimental Treatment
Group I: TYRA-300 0.50 mg/kgExperimental Treatment1 Intervention
TYRA-300 is provided as sprinkle capsules/mini-tablets. The total dose will be calculated based on the participant's weight. Weight adjustments will be made every 3 months.
Group II: TYRA-300 0.375 mg/kgExperimental Treatment1 Intervention
TYRA-300 is provided as sprinkle capsules/mini-tablets. The total dose will be calculated based on the participant's weight. Weight adjustments will be made every 3 months.
Group III: TYRA-300 0.25 mg/kgExperimental Treatment1 Intervention
TYRA-300 is provided as sprinkle capsules/mini-tablets. The total dose will be calculated based on the participant's weight. Weight adjustments will be made every 3 months.
Group IV: TYRA-300 0.125 mg/kgExperimental Treatment1 Intervention
TYRA-300 is provided as sprinkle capsules/mini-tablets. The total dose will be calculated based on the participant's weight. Weight adjustments will be made every 3 months.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Rare Disease ResearchKissimmee, FL
Rare Disease ResearchAtlanta, GA
Rare Disease ResearchHillsborough, NC
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Who Is Running the Clinical Trial?
Tyra Biosciences, IncLead Sponsor
References
Achondroplasia: effectiveness of an orthosis in reducing deformity of the spine. [2007]Deformity of the spine and its complications have long been accepted as characteristics of achondroplasia. We have sought to prevent these with a spinal orthosis. This report includes a description of the orthosis and an analysis of its use in achondroplastic children and adults. Nineteen dwarfs between 11 and 52 months of age were fitted with a light truncal polyform orthosis. The effect on the thoracolumbar (TL) and lumbosacral curves (LS) in the seated and standing child were compared by measurements made from lateral roentgenograms with and without the orthosis. The group mean reduction in TL curve of the seated dwarfs was 23 degrees (range 2 degrees to 73 degrees) and the reduction in the LS curve in the standing position was 15 degrees (range 1 degree to 44 degrees). Seventeen older children aged 4-1/2 to 11-2/3 years were equipped with an aluminum version of the orthosis. Their TL curve sitting was reduced by a mean of 31 degrees (range 6 degrees to 45 degrees) and their LS curve standing was decreased by 16 degrees (range 6 degrees to 30 degrees). Thirty-one achondroplastic children and adults were braced for back pain and/or neurologic deficits. Most were relieved of their symptoms to some degree. These and other data lead us to conclude that this form of treatment reduces deformity and alleviates symptoms.
[Posterior osteotomy and decompression for spinal deformity in patients with achondroplasia]. [2011]to evaluate the outcome of surgical treatment for spinal deformity in patients with achondroplasia.
Growth Modulation by Tension Band Plate in Achondroplasia With Varus Knee Deformity: Comparison of Gait Analysis Measurements. [2023]Limited evidence exists concerning growth modulation by tension band plate (TBP) to correct varus deformity in patients with achondroplasia with limited growth due to FGFR3 gene mutation. We evaluated the efficacy of TBP in children with achondroplasia with genu varum and reported the static radiographic and dynamic motion data to determine parameters that impact the rate of deformity correction.
Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial. [2020]There are no effective therapies for achondroplasia. An open-label study suggested that vosoritide administration might increase growth velocity in children with achondroplasia. This phase 3 trial was designed to further assess these preliminary findings.
Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model. [2020]Achondroplasia (ACH) is the most frequent form of dwarfism and is caused by gain-of-function mutations in the fibroblast growth factor receptor 3-encoding (FGFR3-encoding) gene. Although potential therapeutic strategies for ACH, which aim to reduce excessive FGFR3 activation, have emerged over many years, the use of tyrosine kinase inhibitor (TKI) to counteract FGFR3 hyperactivity has yet to be evaluated. Here, we have reported that the pan-FGFR TKI, NVP-BGJ398, reduces FGFR3 phosphorylation and corrects the abnormal femoral growth plate and calvaria in organ cultures from embryos of the Fgfr3Y367C/+ mouse model of ACH. Moreover, we demonstrated that a low dose of NVP-BGJ398, injected subcutaneously, was able to penetrate into the growth plate of Fgfr3Y367C/+ mice and modify its organization. Improvements to the axial and appendicular skeletons were noticeable after 10 days of treatment and were more extensive after 15 days of treatment that started from postnatal day 1. Low-dose NVP-BGJ398 treatment reduced intervertebral disc defects of lumbar vertebrae, loss of synchondroses, and foramen-magnum shape anomalies. NVP-BGJ398 inhibited FGFR3 downstream signaling pathways, including MAPK, SOX9, STAT1, and PLCγ, in the growth plates of Fgfr3Y367C/+ mice and in cultured chondrocyte models of ACH. Together, our data demonstrate that NVP-BGJ398 corrects pathological hallmarks of ACH and support TKIs as a potential therapeutic approach for ACH.