Patient case (clinical description): A 3-year-old girl is brought to the clinic by her parents for assessment of her short stature. Physical examination reveals short limbs and a relatively large head. She has a flat nasal bridge and a small midface. The girl's father exhibits similar physical features; however, her mother looks normal. The genetic testing reveals an autosomal dominant point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene consistent with achondroplasia in both father and the child. The girl has not received any treatment yet, and it is her first visit after immigration to the US. The other mental and developmental examinations are unremarkable.

Patient's own account: I just brought my little 3-year-old girl to the clinic to have her checked up by the doctor. I was worried sick because she was smaller than her classmates. The lovely doctor performed a physical exam and she told me that she has short limbs and a larger head. My girl also has a flat nasal bridge and a small midface. My baby just has the face of her father, unlike me! They performed some genetic testing on my child and my husband and found out that both my husband and her have a mutation of the FGFR3 gene, which led the doctor to diagnose them with dwarfism. My baby never received any treatment and it was our first visit to the doctor since we arrived in the US. The other tests regarding her mental and physical development were perfectly fine.

Clinical trial: A Study Of Safety, Tolerability And Effectiveness Of Recifercept In Children With Achondroplasia

Eligibility criteria:
Inclusion Criteria:

          -  Main cohort: Aged ≥2 years to <11 years (up to the day before 11th birthday inclusive)
             at time of enrollment; or exploratory cohort: aged ≥3 months to <2 years (up to the
             day before 2nd birthday inclusive) at time of enrollment

          -  Documented, confirmed genetic diagnosis of achondroplasia from historical medical
             records prior to entry into this trial (test must have been performed at a laboratory
             fully accredited for genetic testing under local regulations).

          -  Completed the C4181001 natural history study with at least 2 valid height/length
             measurements (at least 3 months apart) prior to enrollment in this study. One of these
             measurement timepoints must be within the 3 months prior to enrollment in C4181005.

          -  Tanner stage 1 based on investigator assessment during physical examination (must
             include assessment of breast development for females, testicular stage for males).

          -  Able to stand independently for height measurements (if ≥2 years of age at
             enrollment).

          -  If aged <2 years at enrollment, has a documented historical MRI brain/cervical spine
             performed in the previous 12 months.

        Exclusion Criteria:

          -  Presence of co-morbid conditions or circumstances that, in the opinion of the
             investigator, would affect interpretation of growth data or ability to complete the
             trial procedures.

          -  Other medical or psychiatric condition including recent (within the past year) or
             active suicidal ideation/behavior or laboratory abnormality that may increase the risk
             of study participation or, in the investigator's judgment, make the participant
             inappropriate for the study.

          -  Presence of severe obesity (BMI >95th percentile on Hoover-Fong BMI charts)
             [Hoover-Fong et al, 2008].14

          -  Known closure of long bone growth plates (cessation of height growth).

          -  Body weight <7 kg or >30 kg.

          -  Severe renal impairment (eGFR <60 mL/min/1.73m2) or hepatic impairment (AST/ALT >1.5
             ULN).

          -  History of hypersensitivity to study intervention or any excipients.

          -  History of any prior treatment with human growth hormone or related products
             (including insulin-like growth factor 1 [IGF-1]).

          -  History of receipt of any treatment that are known to potentially affect growth
             (including oral steroids >5 days in the last 6 months, high dose inhaled
             corticosteroids (>800 mcg/day beclametasone equivalent) and medication for attention
             deficit hyperactivity disorder).

          -  History of limb lengthening surgery (defined as distraction
             osteogenesis/Ilizarov/callostasis technique following submetaphyseal osteotomy to
             extend bone length).

          -  Any limb lengthening/corrective orthopaedic surgery planned at any point during the
             trial period.

          -  Less than 6 months since fracture or surgical procedure of any bone determined from
             the screening visit date.

          -  Presence of any internal guided growth plates/devices.

          -  History of removal of internal guided growth plates/devices within less than 6 months.

          -  History of receipt of any investigational product for achondroplasia or that may
             affect growth/interpretation of growth parameters.

          -  History of receipt of an investigational product (not for achondroplasia/growth
             affecting) within the last 30 days or 5 half-lives (whichever is longer).
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 3 Months old.
Subject must be at most 10 Years

Eligibility (NLI label): Entailment