TYRA-300 for Achondroplasia

Recruiting at 2 trial locations

Overseen By Kate Hogg Call

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Tyra Biosciences, Inc

Must not be taking: Cyp3A4 inhibitors/inducers

Disqualifiers: Endocrine conditions, Limb surgery, 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: 6

92 Participants Needed

What You Need to Know Before You Apply

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. ^{1 2 3 4 5}

Who Is on the Research Team?

Doug Warner, MD

Principal Investigator

Tyra Biosciences

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• TYRA-300

Trial Overview 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.

How Is the Trial Designed?

Group I: TYRA-300 0.50 mg/kg Experimental Treatment 1 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/kg Experimental Treatment 1 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/kg Experimental Treatment 1 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/kg Experimental Treatment 1 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.

Who Is Running the Clinical Trial?

Tyra Biosciences, Inc

Lead Sponsor

Trials

4

Recruited

500+

Published Research Related to This Trial

A spinal orthosis was tested on 19 achondroplastic children aged 11 to 52 months, resulting in a significant mean reduction of 23 degrees in the thoracolumbar curve and 15 degrees in the lumbosacral curve, indicating effective correction of spinal deformities.

In a larger group of 31 achondroplastic children and adults, the orthosis not only reduced spinal deformities but also provided symptom relief for back pain and neurological deficits, demonstrating its efficacy as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Achondroplasia: effectiveness of an orthosis in reducing deformity of the spine. Siebens, AA., Hungerford, DS., Kirby, NA.[2007]

In a study of 6 patients with achondroplasia, surgical treatment involving posterior osteotomy and decompression effectively corrected thoracolumbar kyphosis from an average of 53.3° to 13.3°, achieving a 75% correction rate.

Patients also showed significant improvement in neurological function, with average JOA scores increasing from 4.5 to 8.5 points after surgery, indicating the procedure's efficacy in addressing both spinal deformity and associated neurological deficits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Posterior osteotomy and decompression for spinal deformity in patients with achondroplasia]. Sun, W., Zhang, JG., Qiu, GX., et al.[2011]

In a study of 22 children with achondroplasia and genu varum, tension band plate (TBP) surgery effectively corrected knee deformities, with significant improvements in radiographic measurements over an average follow-up of 24.5 months.

Younger patients (average age 6.5 years) had better outcomes, highlighting the importance of early intervention for successful correction of varus deformities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Growth Modulation by Tension Band Plate in Achondroplasia With Varus Knee Deformity: Comparison of Gait Analysis Measurements. Ulusaloglu, AC., Asma, A., Silva, LC., et al.[2023]

In a phase 3 trial involving 121 children with achondroplasia, vosoritide significantly increased growth velocity by an average of 1.57 cm/year compared to placebo, demonstrating its efficacy as a treatment.

The treatment was well-tolerated, with no serious adverse events linked to vosoritide, although the long-term effects and impact on final adult height remain unknown.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial. Savarirayan, R., Tofts, L., Irving, M., et al.[2020]

The pan-FGFR tyrosine kinase inhibitor NVP-BGJ398 effectively reduces FGFR3 hyperactivity, leading to improvements in bone growth and structure in a mouse model of achondroplasia after just 10 days of treatment.

NVP-BGJ398 not only corrects abnormalities in the growth plate and skeleton but also inhibits key signaling pathways associated with FGFR3, suggesting it could be a promising therapeutic option for treating achondroplasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model. Komla-Ebri, D., Dambroise, E., Kramer, I., et al.[2020]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Achondroplasia: effectiveness of an orthosis in reducing deformity of the spine. [2007]

2. China pubmed.ncbi.nlm.nih.gov

[Posterior osteotomy and decompression for spinal deformity in patients with achondroplasia]. [2011]

3. United States pubmed.ncbi.nlm.nih.gov

Growth Modulation by Tension Band Plate in Achondroplasia With Varus Knee Deformity: Comparison of Gait Analysis Measurements. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model. [2020]