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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04638153
Registration number
NCT04638153
Ethics application status
Date submitted
15/09/2020
Date registered
20/11/2020
Date last updated
15/02/2024
Titles & IDs
Public title
A Study Of Safety, Tolerability And Effectiveness Of Recifercept In Children With Achondroplasia
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Scientific title
A PHASE 2 MULTIPLE DOSE, RANDOMIZED STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND EFFICACY OF RECIFERCEPT IN CHILDREN WITH ACHONDROPLASIA
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Secondary ID [1]
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2020-001189-13
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Secondary ID [2]
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C4181005
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Achondroplasia
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Condition category
Condition code
Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Musculoskeletal
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Other muscular and skeletal disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Other interventions - Recifercept
Experimental: Low Dose - Low Dose
Experimental: Medium Dose - Medium Dose
Experimental: High Dose - High Dose
Experimental: PK Phase 2 Formulation - Phase 2 formulation [process 1c] 3mg/kg
Experimental: PK Phase 3 Formulation - Phase 3 formulation [process 2] 3mg/kg
Other interventions: Recifercept
Recifercept
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Intervention code [1]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
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Assessment method [1]
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Treatment-related AE was any untoward medical occurrence attributed to study intervention in a participant who received study intervention. 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 AE is defined as an AE with onset date occurring during the on-treatment period. Relatedness to recifercept was assessed by the investigator (Yes/No).
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Timepoint [1]
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The first dose up to 28 to 35 days after the last dose of study intervention (13 months)
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Primary outcome [2]
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Least Square Mean of Change From Baseline Height Growth at Month 3, Month 6, Month 9, and Month 12
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Assessment method [2]
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Height growth was defined as the ratio of observed change from baseline in standing height to the expected change from baseline in the reference population.
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Timepoint [2]
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Baseline, Month 3, Month 6, Month 9, and Month 12
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Secondary outcome [1]
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Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12
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Assessment method [1]
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Pulse rate measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (eg, television, cell phones) where possible (with consideration of the age of the child). Pulse rate was summarized by treatment in accordance with the sponsor reporting standards.
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Timepoint [1]
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Baseline, Month 3, Month 6, Month 9, and Month 12
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Secondary outcome [2]
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Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12
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Assessment method [2]
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Respiratory rate was obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Respiratory rate was summarized by treatment in accordance with the sponsor reporting standards.
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Timepoint [2]
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Baseline, Month 3, Month 6, Month 9, and Month 12
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Secondary outcome [3]
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Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12
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Assessment method [3]
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Blood pressure measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (eg, television, cell phones) where possible (with consideration of the age of the child). Supine systolic blood pressure (SBP) and diastolic blood pressure (DBP) were summarized by treatment in accordance with the sponsor reporting standards.
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Timepoint [3]
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Baseline, Month 3, Month 6, Month 9, and Month 12
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Secondary outcome [4]
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Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12
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Assessment method [4]
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Temperature was obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Temperature measurements were summarized by treatment in accordance with the sponsor reporting standards.
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Timepoint [4]
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Baseline, Month 3, Month 6, Month 9, and Month 12
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Secondary outcome [5]
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Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12
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Assessment method [5]
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A physical examination included, at a minimum, assessments of the cardiovascular, respiratory, gastrointestinal systems and skin. Physical examination assessments were summarized by treatment in accordance with the sponsor reporting standards.
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Timepoint [5]
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Month 3, Month 6, Month 9, and Month 12
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Secondary outcome [6]
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Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
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Assessment method [6]
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Participants with laboratory abnormalities that met pre-specified criteria included following parameters: hematology (corpuscular volume, corpuscular hemoglobin, corpuscular hemoglobin concentration, platelet, leukocytes, lymphocytes, neutrophils, eosinophils, and monocytes), and chemistry (bilirubin, alkaline phosphatase, albumin, urea nitrogen, urate, potassium, phosphate, bicarbonate).
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Timepoint [6]
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Baseline to Month 12
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Secondary outcome [7]
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Pre-Dose Serum Concentration (Ctrough) of Recifercept
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Assessment method [7]
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Ctrough was defined as pre-dose serum concentration during dosing and observed directly from data.
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Timepoint [7]
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Pre-dose on Day(s) 4, 8, 15, 29, 61, 91, 183, 273, 365
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Secondary outcome [8]
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Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) of Recifercept
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Assessment method [8]
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The immunogenicity was measured by presence of ADA and NAb in participants treated with recifercept and summarized by dose regimen.
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Timepoint [8]
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The first dose up to 28 to 35 days after the last dose of study intervention (13 months)
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Secondary outcome [9]
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Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12
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Assessment method [9]
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Sitting/standing height ratio was the ratio of sitting height to standing height.
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Timepoint [9]
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Baseline, Month 3, Month 6, Month 9, and Month 12
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Secondary outcome [10]
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Least Square Mean of Change From Baseline Arm Span to Standing Height/Length Difference at Month 3, Month 6, Month 9, and Month 12
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Assessment method [10]
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Arm span to standing height/length difference was the difference between arm span and standing height.
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Timepoint [10]
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Baseline, Month 3, Month 6, Month 9, and Month 12
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Secondary outcome [11]
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Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12
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Assessment method [11]
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Knee height : lower segment ratio was the ratio of knee to heel length to the difference between standing height and sitting height.
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Timepoint [11]
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Baseline, Month 3, Month 6, Month 9, and Month 12
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Secondary outcome [12]
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Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12
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Assessment method [12]
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Head circumference or the occipito-frontal circumference is the greatest of the cranial dimensions which passes around the forehead anteriorly and the external occipital protruberance posteriorly. It is a routine part of the physical examination of a child and is of great importance in detecting abnormal patterns of cranial growth. Occipito-frontal circumference data were summarized for each treatment arm.
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Timepoint [12]
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Baseline, Month 3, Month 6, Month 9, and Month 12
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Secondary outcome [13]
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Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12
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Assessment method [13]
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Ratio of occipito-frontal distance to occipito-mid-face measurements was summarized for each treatment arm.
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Timepoint [13]
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Baseline, Month 3, Month 6, Month 9, and Month 12
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Secondary outcome [14]
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Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12
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Assessment method [14]
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Height Standard Deviation Score (SDS) (z-score) was calculated as the difference between mean observed standing height at each visit and mean value of reference population divided by standard deviation of reference population. SDS indicates how similar the participant was to the reference population.
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Timepoint [14]
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Baseline, Month 3, Month 6, Month 9, and Month 12
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Secondary outcome [15]
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Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12
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Assessment method [15]
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Fixed flexion angles at elbow data were presented for each treatment arm. An average of a participant's elbow extension measurements over a visit was computed.
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Timepoint [15]
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Baseline, Month 3, Month 6, Month 9, and Month 12
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Secondary outcome [16]
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Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12
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Assessment method [16]
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Body Mass Index (BMI) = Weight (kg)/[(Standing Height (m))^2]. Standing height and weight were averaged over a visit before BMI was computed.
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Timepoint [16]
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Baseline, Month 3, Month 6, Month 9, and Month 12
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Secondary outcome [17]
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Change From Baseline in Waist : Chest Circumference Ratio at Month 9 and Month 12
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Assessment method [17]
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Waist : Chest Ratio = Waist Circumference / Chest Circumference. Waist and chest circumference were averaged over a visit before waist : chest circumference ratio was computed.
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Timepoint [17]
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Baseline, Month 9, and Month 12
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Secondary outcome [18]
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Change From Baseline in Apnea-Hypopnea Index (AHI) at Month 12
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Assessment method [18]
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The apnea-hypopnea index (AHI) is the average of the apneic and hypopneic episodes per hour of sleep, which is measured to assess obstructive sleep apnea (OSA). An AHI score of 1 to 4.9 events/hour is mild OSA, 5 to 9.9 events/hour is moderate, and more than 9 events/hour is severe in pediatric population.
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Timepoint [18]
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Baseline and Month 12
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Secondary outcome [19]
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Change From Baseline in Desaturation Index at Month 12
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Assessment method [19]
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Desaturation index is one of the polysomnography parameters to assess obstructive sleep apnea. It refers to the average number of desaturation episodes occurring per hour, where desaturation episodes are defined as a decrease in the mean oxygen saturation of =3% (over the last 120 seconds) that lasts for at least 10 seconds.
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Timepoint [19]
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Baseline and Month 12
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Secondary outcome [20]
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Change From Baseline in Polysomnography Other Parameters at Month 12
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Assessment method [20]
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Polysomnography refers to a systematic process used to collect physiologic parameters during sleep. Polysomnography other parameters included total sleep time spent with oxygen saturation (SaO2) < 90% (T90), total sleep time spent with end-tidal carbon dioxide (EtCO2) >50 mm Hg.
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Timepoint [20]
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Baseline and Month 12
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Secondary outcome [21]
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Change From Baseline in SaO2 Nadir at Month 12
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Assessment method [21]
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SaO2 measures the percentage of oxyhemoglobin (oxygen-bound hemoglobin) in the blood. SaO2 nadir refers to lowest SaO2.
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Timepoint [21]
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Baseline and Month 12
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Eligibility
Key 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.
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Minimum age
3
Months
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Maximum age
10
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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.
- Moderate or severe renal impairment CrCL GFR <60 mL/min/1.73m2 (Calculated GFR based
on updated "bedside" Schwartz formula for pediatric patients (CrCL (mL/min/1.73 m2) =
0.413 * Height (cms)/ Serum cr (mg/dL) 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).
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Study design
Purpose of the study
Prevention
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people assessing the outcomes
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Terminated
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
2/12/2020
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
27/03/2023
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Sample size
Target
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Accrual to date
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Final
60
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Murdoch Children's Research Institute - Melbourne
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Recruitment hospital [2]
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Murdoch Children's Research Institute - Parkville
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Recruitment postcode(s) [1]
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3052 - Melbourne
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Recruitment postcode(s) [2]
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3052 - Parkville
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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Country [2]
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United States of America
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State/province [2]
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Delaware
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Country [3]
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United States of America
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State/province [3]
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Texas
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Country [4]
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Belgium
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State/province [4]
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Edegem
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Country [5]
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Belgium
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State/province [5]
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Leuven
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Country [6]
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Denmark
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State/province [6]
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Copenhagen NV
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Country [7]
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Italy
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State/province [7]
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Roma
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Country [8]
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Japan
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State/province [8]
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Osaka
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Country [9]
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Japan
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State/province [9]
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Okayama
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Country [10]
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Portugal
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State/province [10]
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Coimbra
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Country [11]
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Spain
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State/province [11]
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Alava
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Pfizer
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
Approximately 63 participants will be randomized to one of three doses to receive Recifercept
either
- Low Dose
- Medium Dose
- High Dose
Participants will will attend the clinic at baseline and at Day 1, 4, 8, 15, 29 & then Month
2, 3 6, 9 & 12. Assessments include safety, blood sampling, physical examination, vital
signs, anthropometric body measurements & patient/caregiver quality of life questionnaires
Participants will received treatment with Recifercept for 12 months. All participants who
complete the study and in the opinion of the investigator, continue to have a positive
risk:benefit profile, will be offered to enroll into an open-label extension (OLE) study.
A PK cohort will include 12 participants who will randomly receive a single dose of 3 mg/kg
of Phase 2 study (process 1c) formulation and a single dose of 3 mg/kg of the proposed Phase
3 (process 2) study formulation in a cross over study. Dose of the cohort could be changed
due to emerging safety and efficacy data in the study.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT04638153
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Pfizer CT.gov Call Center
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Address
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Pfizer
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04638153
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