Achondroplasia
Conditions
Interventions
Intervention: Recifercept
Arms: Low Dose, Medium Dose, High Dose,
PK cohort: Phase 2 formulation [process 1c] 3 mg/kg, Phase 3 formulation [process 2] 3 mg/kg
Sponsors
Kawai Norisuke
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria: Main cohort: Aged >=2 years to =3 months to =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
Exclusion criteria: 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 30 kg. *Moderate or Severe renal impairment CrCL GFR 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Outcome Measures : 1.Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) [ Time Frame: Baseline (Day 0) up to 365 days after last dose of study medication ] Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 365 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to Recifercept was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. 2.Height [ Time Frame: Change in height from baseline up to 365 days after last dose ] Increase in height growth above expected in reference population 3. PK Cohort: PK after single doses of 2 formulations [ Time Frame: Baseline to Day 57 ] To evaluate the PK of single subcutaneous doses of 2 formulations (process 1c and process 2) of recifercept | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Outcome Measures : 1.Number of Participants With Change From Baseline in Vital Signs [ Time Frame: Baseline up to end of treatment (Day 365) ] Following parameters were analyzed for examination of vital signs: systolic and diastolic blood pressure, respiratory rate, radial pulse and body temperature. 2.Number of Participants With Change From Baseline in Physical Examination [ Time Frame: Baseline up to end of treatment (Day 365) ] Following parameters were analyzed for examination of systems; A physical examination will include, at a minimum, assessments of the cardiovascular, respiratory, gastrointestinal systems and skin. 3.Number of Participants With Laboratory Abnormalities [ Time Frame: Baseline up to end of treatment (Day 365) ] Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid albumin, total protein) 4.Pharmacokinetics - Apparent Clearance (CL/F) [ Time Frame: Day(s) 4, 8, 15, 29, 61, 91, 183, 365 ] Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. 5.Number of Participants With Anti-Drug Antibody (ADA) [ Time Frame: Baseline up to end of treatment (Day 365) ] The percentage of participants with positive ADA and neutralizing antibodies will be summarized for each treatment arm. 6.Change from Baseline in Standing & Sitting Height [ Time Frame: Baseline, 3, 6, 9 & 12 Months ] Sitting height/standing height ratio 7.Ch | — |
Countries
Australia, Belgium, Denmark, Italy, Japan, Portugal, Spain, United States
Contacts
Public ContactClinical Trials Information Desk
Pfizer R&D Japan G.K.
Outcome results
None listed