Achondroplasia
Conditions
Brief summary
The purpose of this study is to learn about the study medicine (called recifercept) in people with achondroplasia. Achondroplasia is a very rare disease and patients of achondroplasia have short arms and legs. The study will include data already collected from a recifercept clinical trial and data collected from a separate study of achondroplasia. This study will compare patient experiences and will help the investigators determine if the study medicine, recifercept, is effective.
Interventions
OTHERRecifercept
Patients received recifercept intervention in the phase 2 clinical trial
Sponsors
Pfizer
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
3 Months to 10 Years
Healthy volunteers
No
Inclusion criteria
* All patients from Study C4181005 who have completed Visits 1 through 11 (at D183) will be included in this project. To construct a concurrent external control, patients from Study C4181001 will need to meet the following inclusion criteria from Study C4181005 to be eligible for inclusion: * Documented, confirmed genetic diagnosis of achondroplasia from historical medical records (test must have been performed at a laboratory fully accredited for genetic testing under local regulations) * Aged ≥ 3 months to \<11 years (up to the day before 11th birthday inclusive) at time of enrollment into the observational natural history study. * Havecompleted at least 2 valid height/length measurements (at least 3 months apart) * Assessed for Tanner stage 1 during physical examination before or at enrollment (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. * Have at least 6 months of available follow-up data after enrollment into the natural history study
Exclusion criteria
* Patients meeting any of the following criteria will not be included in the study: * Presence of severe obesity (BMI\>95% percentile on Hoover-Fong BMI charts); * Body weight \<7kg or \>30kg * History of chronic kidney disease (CKD) or renal impairment * History of receipt of any treatment that are known to potentially affect growth (including oral steroids \> 5 days in the last 6 months before enrollment, high dose inhaled corticosteroids (\>800 mcg/day beclametasone equivalent) and medication for attention deficient hyperactivity disorder. * Less than 6 months since fracture or surgical procedure of any bone determined from the baseline visit date. * Presence of any internal guided growth plates/devices * History of removal of internal guided growth plates/devices within 6 months prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Height Growth at Month 3 | Baseline, Month 3 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)] | Height growth was defined as ratio of observed change from baseline in standing height (centimeter) to expected change from baseline (centimeter) in reference population. For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing. |
| Mean Height Growth at Month 6 | Baseline, Month 6 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)] | Height growth was defined as ratio of observed change from baseline in standing height (centimeter) to expected change from baseline (centimeter) in reference population. For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing. |
| Mean Height Growth at Month 9 | Baseline, Month 9 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)] | Height growth was defined as ratio of observed change from baseline in standing height (centimeter) to expected change from baseline (centimeter) in reference population. For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing. |
| Mean Height Growth at Month 12 | Baseline, Month 12 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)] | Height growth was defined as ratio of observed change from baseline in standing height (centimeter) to expected change from baseline (centimeter) in reference population. For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9 and 12 | Baseline, Months 3, 6, 9, 12 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)] | Arm span to standing height or length difference was defined as absolute value (arm length \[centimeter\] - standing height \[centimeter\]). For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing. |
| Number of Participants With Other Achondroplasia Related Orthopedic Complications | C4181005 cohorts: 12 months; C4181001 cohort: 5 years [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)] | Other achondroplasia related orthopedic complications included otitis media, otitis media acute, hydrocephalus and obstructive sleep apnea syndrome. |
| Mean Change From Baseline in Knee Height: Lower Segment Ratio at Months 3, 6, 9 and 12 | Baseline, Months 3, 6, 9, 12 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)] | Knee height: lower segment ratio was the ratio of knee to heel length to the difference between standing height and sitting height. For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing. |
| Mean Change From Baseline in Height Standard Deviation Score (Z-Score) at Months 3, 6, 9, 12 | Baseline, Months 3, 6, 9, 12 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)] | Z-score was calculated as the difference between mean observed standing height at specified visit and mean value of reference population divided by standard deviation of reference population. Z score indicated how similar the participant was to the reference population. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing. |
| Number of Participants With Achondroplasia Related Orthopedic Complications | C4181005 cohorts: 12 months; C4181001 cohort: 5 years [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)] | Achondroplasia related orthopedic complications included lordosis, kyphosis, small foramen magnum: foramen magnum is slightly narrow and the spinal cord is slightly compressed at the level, foramen magnum stenosis, foramen magnum stenosis with associated c1-c2 secondary myelopathy, foramen magnum stenosis with mild posterior deformity of bulbospinal union, foramen magnum stenosis without spinal cord alteration, cervical myelomalacia; bulbar compression, marked stenosis of the foramen magnum with evident compression of bulb and bulb-medulla passage, mild foramen magnus stenosis, mild stenosis of foramen magnum, moderate to severe narrowing of the foramen magnum, severe stenosis at foramen magnum and stenosis foramen magnum. |
Countries
United States
Participant flow
Recruitment details
Data from eligible participants from C4181005 (NCT04638153) study and from C4181001 (NCT03794609) study were extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months).
Participants by arm
| Arm | Count |
|---|---|
| C4181005 Cohort: Recifercept 1 mg/kg QW Eligible participants who received recifercept 1 mg/kg QW subcutaneously for 12 months in study C4181005 were included in this arm. Data from these participants were observed in this retrospective observational study. | 20 |
| C4181005 Cohort: Recifercept 2 mg/kg BIW Eligible participants who received recifercept 2 mg/kg BIW subcutaneously for 12 months in study C4181005 were included in this arm. Data from these participants were observed in this retrospective observational study. | 19 |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD Eligible participants who received recifercept 1.5 mg/kg QD subcutaneously for 12 months in study C4181005 were included in this arm. Data from these participants were observed in this retrospective observational study. | 18 |
| C4181001 Cohort Eligible participants from study C4181001 who met the eligibility criteria for study C4181005 and had at least 6 months and up to 5 years follow-up data were included in this arm. Data from these participants were observed in this retrospective observational study. | 191 |
| Total | 248 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | At sponsor's request | 0 | 0 | 0 | 95 |
| Overall Study | Inclusion/Exclusion criteria | 0 | 0 | 0 | 5 |
| Overall Study | Increased age moving to different baseline study with prospects of moving to intervention in future | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 2 |
| Overall Study | Moved to another observational study | 0 | 0 | 0 | 1 |
| Overall Study | The child was enrolled in an interventional study | 0 | 0 | 0 | 55 |
| Overall Study | The child went to lower limbs elongation surgery in few weeks' time | 0 | 0 | 0 | 1 |
| Overall Study | The family wished to pursue a prescription a voxzogo instead of waiting for phase 3 | 0 | 0 | 0 | 2 |
| Overall Study | Wish of the child, or of the child's parent(S)/legal guardian(S), to withdrew from the study | 0 | 0 | 0 | 27 |
Baseline characteristics
| Characteristic | C4181005 Cohort: Recifercept 1 mg/kg QW | Total | C4181005 Cohort: Recifercept 2 mg/kg BIW | C4181005 Cohort: Recifercept 1.5 mg/kg QD | C4181001 Cohort |
|---|---|---|---|---|---|
| Age, Continuous | 5.75 Years STANDARD_DEVIATION 2.84 | 4.86 Years STANDARD_DEVIATION 2.61 | 5.16 Years STANDARD_DEVIATION 2.59 | 5.83 Years STANDARD_DEVIATION 2.31 | 4.65 Years STANDARD_DEVIATION 2.59 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 15 Participants | 0 Participants | 2 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 231 Participants | 19 Participants | 15 Participants | 181 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 3 Participants | 46 Participants | 0 Participants | 2 Participants | 41 Participants |
| Race/Ethnicity, Customized Race Black or African American | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Multiracial | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Not reported | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 5 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized Race White | 15 Participants | 191 Participants | 19 Participants | 14 Participants | 143 Participants |
| Sex: Female, Male Female | 9 Participants | 103 Participants | 9 Participants | 6 Participants | 79 Participants |
| Sex: Female, Male Male | 11 Participants | 145 Participants | 10 Participants | 12 Participants | 112 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Mean Height Growth at Month 12
Height growth was defined as ratio of observed change from baseline in standing height (centimeter) to expected change from baseline (centimeter) in reference population. For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing.
Time frame: Baseline, Month 12 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)]
Population: FAS included all enrolled participants who met the inclusion and exclusion criteria for the study. Here, Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| C4181005 Cohort: Recifercept 1 mg/kg QW | Mean Height Growth at Month 12 | 0.94 Ratio | Standard Deviation 0.298 |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Mean Height Growth at Month 12 | 1.06 Ratio | Standard Deviation 0.217 |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Mean Height Growth at Month 12 | 0.84 Ratio | Standard Deviation 0.036 |
| C4181001 Cohort | Mean Height Growth at Month 12 | 1.10 Ratio | Standard Deviation 0.376 |
Primary
Mean Height Growth at Month 3
Height growth was defined as ratio of observed change from baseline in standing height (centimeter) to expected change from baseline (centimeter) in reference population. For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing.
Time frame: Baseline, Month 3 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)]
Population: FAS included all enrolled participants who met the inclusion and exclusion criteria for the study. Here, Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| C4181005 Cohort: Recifercept 1 mg/kg QW | Mean Height Growth at Month 3 | 1.11 Ratio | Standard Deviation 0.487 |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Mean Height Growth at Month 3 | 0.84 Ratio | Standard Deviation 0.548 |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Mean Height Growth at Month 3 | 0.75 Ratio | Standard Deviation 0.707 |
| C4181001 Cohort | Mean Height Growth at Month 3 | 1.07 Ratio | Standard Deviation 0.82 |
Primary
Mean Height Growth at Month 6
Height growth was defined as ratio of observed change from baseline in standing height (centimeter) to expected change from baseline (centimeter) in reference population. For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing.
Time frame: Baseline, Month 6 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)]
Population: FAS included all enrolled participants who met the inclusion and exclusion criteria for the study. Here, Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| C4181005 Cohort: Recifercept 1 mg/kg QW | Mean Height Growth at Month 6 | 0.94 Ratio | Standard Deviation 0.429 |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Mean Height Growth at Month 6 | 1.06 Ratio | Standard Deviation 0.44 |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Mean Height Growth at Month 6 | 1.01 Ratio | Standard Deviation 0.453 |
| C4181001 Cohort | Mean Height Growth at Month 6 | 1.11 Ratio | Standard Deviation 0.567 |
Primary
Mean Height Growth at Month 9
Height growth was defined as ratio of observed change from baseline in standing height (centimeter) to expected change from baseline (centimeter) in reference population. For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing.
Time frame: Baseline, Month 9 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)]
Population: FAS included all enrolled participants who met the inclusion and exclusion criteria for the study. Here, Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| C4181005 Cohort: Recifercept 1 mg/kg QW | Mean Height Growth at Month 9 | 1.01 Ratio | Standard Deviation 0.374 |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Mean Height Growth at Month 9 | 0.97 Ratio | Standard Deviation 0.242 |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Mean Height Growth at Month 9 | 1.03 Ratio | Standard Deviation 0.285 |
| C4181001 Cohort | Mean Height Growth at Month 9 | 1.10 Ratio | Standard Deviation 0.419 |
Secondary
Mean Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9 and 12
Arm span to standing height or length difference was defined as absolute value (arm length \[centimeter\] - standing height \[centimeter\]). For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing.
Time frame: Baseline, Months 3, 6, 9, 12 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)]
Population: FAS included all enrolled participants who met the inclusion and exclusion criteria for the study. Here, Number Analyzed signifies participants evaluable for specific timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C4181005 Cohort: Recifercept 1 mg/kg QW | Mean Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9 and 12 | Month 3 | 0.46 Centimeter | Standard Deviation 0.956 |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Mean Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9 and 12 | Month 6 | 0.19 Centimeter | Standard Deviation 1.863 |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Mean Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9 and 12 | Month 9 | 0.64 Centimeter | Standard Deviation 0.89 |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Mean Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9 and 12 | Month 12 | 0.47 Centimeter | Standard Deviation 1.22 |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Mean Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9 and 12 | Month 6 | 0.72 Centimeter | Standard Deviation 1.028 |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Mean Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9 and 12 | Month 9 | 0.69 Centimeter | Standard Deviation 1.394 |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Mean Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9 and 12 | Month 12 | 1.12 Centimeter | Standard Deviation 1.754 |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Mean Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9 and 12 | Month 3 | 0.02 Centimeter | Standard Deviation 0.879 |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Mean Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9 and 12 | Month 9 | 0.15 Centimeter | Standard Deviation 0.781 |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Mean Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9 and 12 | Month 6 | -0.47 Centimeter | Standard Deviation 1.927 |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Mean Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9 and 12 | Month 12 | 0.20 Centimeter | Standard Deviation 0.707 |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Mean Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9 and 12 | Month 3 | -0.61 Centimeter | Standard Deviation 1.705 |
| C4181001 Cohort | Mean Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9 and 12 | Month 12 | 1.29 Centimeter | Standard Deviation 3.745 |
| C4181001 Cohort | Mean Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9 and 12 | Month 6 | 0.31 Centimeter | Standard Deviation 1.706 |
| C4181001 Cohort | Mean Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9 and 12 | Month 3 | 0.09 Centimeter | Standard Deviation 1.18 |
| C4181001 Cohort | Mean Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9 and 12 | Month 9 | 0.53 Centimeter | Standard Deviation 1.705 |
Secondary
Mean Change From Baseline in Height Standard Deviation Score (Z-Score) at Months 3, 6, 9, 12
Z-score was calculated as the difference between mean observed standing height at specified visit and mean value of reference population divided by standard deviation of reference population. Z score indicated how similar the participant was to the reference population. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing.
Time frame: Baseline, Months 3, 6, 9, 12 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)]
Population: FAS included all enrolled participants who met the inclusion and exclusion criteria for the study. Here, Number Analyzed signifies participants evaluable for specific timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C4181005 Cohort: Recifercept 1 mg/kg QW | Mean Change From Baseline in Height Standard Deviation Score (Z-Score) at Months 3, 6, 9, 12 | Month 3 | 0.03 Z-score | Standard Deviation 0.134 |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Mean Change From Baseline in Height Standard Deviation Score (Z-Score) at Months 3, 6, 9, 12 | Month 6 | -0.03 Z-score | Standard Deviation 0.205 |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Mean Change From Baseline in Height Standard Deviation Score (Z-Score) at Months 3, 6, 9, 12 | Month 9 | 0.00 Z-score | Standard Deviation 0.258 |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Mean Change From Baseline in Height Standard Deviation Score (Z-Score) at Months 3, 6, 9, 12 | Month 12 | -0.03 Z-score | Standard Deviation 0.327 |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Mean Change From Baseline in Height Standard Deviation Score (Z-Score) at Months 3, 6, 9, 12 | Month 6 | 0.03 Z-score | Standard Deviation 0.211 |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Mean Change From Baseline in Height Standard Deviation Score (Z-Score) at Months 3, 6, 9, 12 | Month 9 | -0.02 Z-score | Standard Deviation 0.214 |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Mean Change From Baseline in Height Standard Deviation Score (Z-Score) at Months 3, 6, 9, 12 | Month 12 | 0.07 Z-score | Standard Deviation 0.257 |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Mean Change From Baseline in Height Standard Deviation Score (Z-Score) at Months 3, 6, 9, 12 | Month 3 | -0.04 Z-score | Standard Deviation 0.173 |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Mean Change From Baseline in Height Standard Deviation Score (Z-Score) at Months 3, 6, 9, 12 | Month 9 | 0.02 Z-score | Standard Deviation 0.205 |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Mean Change From Baseline in Height Standard Deviation Score (Z-Score) at Months 3, 6, 9, 12 | Month 6 | -0.00 Z-score | Standard Deviation 0.236 |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Mean Change From Baseline in Height Standard Deviation Score (Z-Score) at Months 3, 6, 9, 12 | Month 12 | -0.24 Z-score | Standard Deviation 0.169 |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Mean Change From Baseline in Height Standard Deviation Score (Z-Score) at Months 3, 6, 9, 12 | Month 3 | -0.02 Z-score | Standard Deviation 0.266 |
| C4181001 Cohort | Mean Change From Baseline in Height Standard Deviation Score (Z-Score) at Months 3, 6, 9, 12 | Month 12 | 0.12 Z-score | Standard Deviation 0.439 |
| C4181001 Cohort | Mean Change From Baseline in Height Standard Deviation Score (Z-Score) at Months 3, 6, 9, 12 | Month 6 | 0.06 Z-score | Standard Deviation 0.355 |
| C4181001 Cohort | Mean Change From Baseline in Height Standard Deviation Score (Z-Score) at Months 3, 6, 9, 12 | Month 3 | 0.03 Z-score | Standard Deviation 0.289 |
| C4181001 Cohort | Mean Change From Baseline in Height Standard Deviation Score (Z-Score) at Months 3, 6, 9, 12 | Month 9 | 0.07 Z-score | Standard Deviation 0.412 |
Secondary
Mean Change From Baseline in Knee Height: Lower Segment Ratio at Months 3, 6, 9 and 12
Knee height: lower segment ratio was the ratio of knee to heel length to the difference between standing height and sitting height. For C4181001 cohort, baseline value was defined as the value recorded at the date of informed consent, whereas for C4181005 cohort the baseline value was the value taken at Day 1 before dosing.
Time frame: Baseline, Months 3, 6, 9, 12 [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)]
Population: FAS included all enrolled participants who met the inclusion and exclusion criteria for the study. Here, Number Analyzed signifies participants evaluable for specific timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C4181005 Cohort: Recifercept 1 mg/kg QW | Mean Change From Baseline in Knee Height: Lower Segment Ratio at Months 3, 6, 9 and 12 | Month 3 | -0.00 Ratio | Standard Deviation 0.02 |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Mean Change From Baseline in Knee Height: Lower Segment Ratio at Months 3, 6, 9 and 12 | Month 6 | -0.00 Ratio | Standard Deviation 0.028 |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Mean Change From Baseline in Knee Height: Lower Segment Ratio at Months 3, 6, 9 and 12 | Month 9 | -0.00 Ratio | Standard Deviation 0.027 |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Mean Change From Baseline in Knee Height: Lower Segment Ratio at Months 3, 6, 9 and 12 | Month 12 | 0.00 Ratio | Standard Deviation 0.028 |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Mean Change From Baseline in Knee Height: Lower Segment Ratio at Months 3, 6, 9 and 12 | Month 6 | -0.02 Ratio | Standard Deviation 0.062 |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Mean Change From Baseline in Knee Height: Lower Segment Ratio at Months 3, 6, 9 and 12 | Month 12 | -0.02 Ratio | Standard Deviation 0.081 |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Mean Change From Baseline in Knee Height: Lower Segment Ratio at Months 3, 6, 9 and 12 | Month 3 | -0.01 Ratio | Standard Deviation 0.052 |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Mean Change From Baseline in Knee Height: Lower Segment Ratio at Months 3, 6, 9 and 12 | Month 9 | -0.02 Ratio | Standard Deviation 0.065 |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Mean Change From Baseline in Knee Height: Lower Segment Ratio at Months 3, 6, 9 and 12 | Month 9 | 0.01 Ratio | Standard Deviation 0.026 |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Mean Change From Baseline in Knee Height: Lower Segment Ratio at Months 3, 6, 9 and 12 | Month 12 | 0.02 Ratio | Standard Deviation 0.023 |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Mean Change From Baseline in Knee Height: Lower Segment Ratio at Months 3, 6, 9 and 12 | Month 3 | 0.02 Ratio | Standard Deviation 0.037 |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Mean Change From Baseline in Knee Height: Lower Segment Ratio at Months 3, 6, 9 and 12 | Month 6 | 0.00 Ratio | Standard Deviation 0.026 |
| C4181001 Cohort | Mean Change From Baseline in Knee Height: Lower Segment Ratio at Months 3, 6, 9 and 12 | Month 12 | -0.01 Ratio | Standard Deviation 0.049 |
| C4181001 Cohort | Mean Change From Baseline in Knee Height: Lower Segment Ratio at Months 3, 6, 9 and 12 | Month 3 | -0.09 Ratio | Standard Deviation 0.864 |
| C4181001 Cohort | Mean Change From Baseline in Knee Height: Lower Segment Ratio at Months 3, 6, 9 and 12 | Month 6 | -0.01 Ratio | Standard Deviation 0.048 |
| C4181001 Cohort | Mean Change From Baseline in Knee Height: Lower Segment Ratio at Months 3, 6, 9 and 12 | Month 9 | -0.01 Ratio | Standard Deviation 0.05 |
Secondary
Number of Participants With Achondroplasia Related Orthopedic Complications
Achondroplasia related orthopedic complications included lordosis, kyphosis, small foramen magnum: foramen magnum is slightly narrow and the spinal cord is slightly compressed at the level, foramen magnum stenosis, foramen magnum stenosis with associated c1-c2 secondary myelopathy, foramen magnum stenosis with mild posterior deformity of bulbospinal union, foramen magnum stenosis without spinal cord alteration, cervical myelomalacia; bulbar compression, marked stenosis of the foramen magnum with evident compression of bulb and bulb-medulla passage, mild foramen magnus stenosis, mild stenosis of foramen magnum, moderate to severe narrowing of the foramen magnum, severe stenosis at foramen magnum and stenosis foramen magnum.
Time frame: C4181005 cohorts: 12 months; C4181001 cohort: 5 years [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)]
Population: FAS included all enrolled participants who met the inclusion and exclusion criteria for the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| C4181005 Cohort: Recifercept 1 mg/kg QW | Number of Participants With Achondroplasia Related Orthopedic Complications | Lordosis | 0 Participants |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Number of Participants With Achondroplasia Related Orthopedic Complications | Kyphosis | 0 Participants |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum is slightly narrow | 0 Participants |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis | 0 Participants |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis with associated c1-c2 secondary myelopathy | 0 Participants |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis with mild posterior deformity of bulbospinal union | 0 Participants |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis without spinal cord alteration | 0 Participants |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis; cervical myelomalacia; bulbar compression | 0 Participants |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Number of Participants With Achondroplasia Related Orthopedic Complications | Marked stenosis of the foramen magnum with evident compression of Bulb and bulb-medulla passage | 0 Participants |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Number of Participants With Achondroplasia Related Orthopedic Complications | Mild foramen magnus stenosis | 0 Participants |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Number of Participants With Achondroplasia Related Orthopedic Complications | Moderate to severe narrowing of the foramen magnum | 0 Participants |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Number of Participants With Achondroplasia Related Orthopedic Complications | Severe stenosis at foramen magnum | 0 Participants |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Number of Participants With Achondroplasia Related Orthopedic Complications | Stenosis foramen magnum | 0 Participants |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis | 0 Participants |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Number of Participants With Achondroplasia Related Orthopedic Complications | Stenosis foramen magnum | 0 Participants |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Number of Participants With Achondroplasia Related Orthopedic Complications | Moderate to severe narrowing of the foramen magnum | 0 Participants |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis; cervical myelomalacia; bulbar compression | 0 Participants |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum is slightly narrow | 0 Participants |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Number of Participants With Achondroplasia Related Orthopedic Complications | Lordosis | 0 Participants |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Number of Participants With Achondroplasia Related Orthopedic Complications | Mild foramen magnus stenosis | 0 Participants |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Number of Participants With Achondroplasia Related Orthopedic Complications | Marked stenosis of the foramen magnum with evident compression of Bulb and bulb-medulla passage | 0 Participants |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis with mild posterior deformity of bulbospinal union | 0 Participants |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis with associated c1-c2 secondary myelopathy | 0 Participants |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Number of Participants With Achondroplasia Related Orthopedic Complications | Kyphosis | 0 Participants |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Number of Participants With Achondroplasia Related Orthopedic Complications | Severe stenosis at foramen magnum | 0 Participants |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis without spinal cord alteration | 0 Participants |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Number of Participants With Achondroplasia Related Orthopedic Complications | Moderate to severe narrowing of the foramen magnum | 0 Participants |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis | 0 Participants |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis with associated c1-c2 secondary myelopathy | 0 Participants |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Number of Participants With Achondroplasia Related Orthopedic Complications | Stenosis foramen magnum | 0 Participants |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis with mild posterior deformity of bulbospinal union | 0 Participants |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis without spinal cord alteration | 0 Participants |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Number of Participants With Achondroplasia Related Orthopedic Complications | Severe stenosis at foramen magnum | 0 Participants |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis; cervical myelomalacia; bulbar compression | 0 Participants |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Number of Participants With Achondroplasia Related Orthopedic Complications | Marked stenosis of the foramen magnum with evident compression of Bulb and bulb-medulla passage | 0 Participants |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Number of Participants With Achondroplasia Related Orthopedic Complications | Mild foramen magnus stenosis | 0 Participants |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Number of Participants With Achondroplasia Related Orthopedic Complications | Lordosis | 0 Participants |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Number of Participants With Achondroplasia Related Orthopedic Complications | Kyphosis | 0 Participants |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum is slightly narrow | 0 Participants |
| C4181001 Cohort | Number of Participants With Achondroplasia Related Orthopedic Complications | Mild foramen magnus stenosis | 1 Participants |
| C4181001 Cohort | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis; cervical myelomalacia; bulbar compression | 1 Participants |
| C4181001 Cohort | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis | 3 Participants |
| C4181001 Cohort | Number of Participants With Achondroplasia Related Orthopedic Complications | Lordosis | 79 Participants |
| C4181001 Cohort | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis without spinal cord alteration | 1 Participants |
| C4181001 Cohort | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis with mild posterior deformity of bulbospinal union | 1 Participants |
| C4181001 Cohort | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum is slightly narrow | 1 Participants |
| C4181001 Cohort | Number of Participants With Achondroplasia Related Orthopedic Complications | Kyphosis | 1 Participants |
| C4181001 Cohort | Number of Participants With Achondroplasia Related Orthopedic Complications | Foramen magnum stenosis with associated c1-c2 secondary myelopathy | 1 Participants |
| C4181001 Cohort | Number of Participants With Achondroplasia Related Orthopedic Complications | Marked stenosis of the foramen magnum with evident compression of Bulb and bulb-medulla passage | 1 Participants |
| C4181001 Cohort | Number of Participants With Achondroplasia Related Orthopedic Complications | Stenosis foramen magnum | 3 Participants |
| C4181001 Cohort | Number of Participants With Achondroplasia Related Orthopedic Complications | Severe stenosis at foramen magnum | 1 Participants |
| C4181001 Cohort | Number of Participants With Achondroplasia Related Orthopedic Complications | Moderate to severe narrowing of the foramen magnum | 1 Participants |
Secondary
Number of Participants With Other Achondroplasia Related Orthopedic Complications
Other achondroplasia related orthopedic complications included otitis media, otitis media acute, hydrocephalus and obstructive sleep apnea syndrome.
Time frame: C4181005 cohorts: 12 months; C4181001 cohort: 5 years [Eligible data extracted and observed in this retrospective cohort study from 19-October-2022 to 16-May-2023 (approximately 7 months)]
Population: FAS included all enrolled participants who met the inclusion and exclusion criteria for the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| C4181005 Cohort: Recifercept 1 mg/kg QW | Number of Participants With Other Achondroplasia Related Orthopedic Complications | Otitis media | 3 Participants |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Number of Participants With Other Achondroplasia Related Orthopedic Complications | Obstructive sleep apnea syndrome | 0 Participants |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Number of Participants With Other Achondroplasia Related Orthopedic Complications | Otitis media acute | 0 Participants |
| C4181005 Cohort: Recifercept 1 mg/kg QW | Number of Participants With Other Achondroplasia Related Orthopedic Complications | Hydrocephalus | 0 Participants |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Number of Participants With Other Achondroplasia Related Orthopedic Complications | Otitis media acute | 1 Participants |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Number of Participants With Other Achondroplasia Related Orthopedic Complications | Hydrocephalus | 0 Participants |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Number of Participants With Other Achondroplasia Related Orthopedic Complications | Otitis media | 1 Participants |
| C4181005 Cohort: Recifercept 2 mg/kg BIW | Number of Participants With Other Achondroplasia Related Orthopedic Complications | Obstructive sleep apnea syndrome | 1 Participants |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Number of Participants With Other Achondroplasia Related Orthopedic Complications | Otitis media acute | 0 Participants |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Number of Participants With Other Achondroplasia Related Orthopedic Complications | Otitis media | 1 Participants |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Number of Participants With Other Achondroplasia Related Orthopedic Complications | Hydrocephalus | 0 Participants |
| C4181005 Cohort: Recifercept 1.5 mg/kg QD | Number of Participants With Other Achondroplasia Related Orthopedic Complications | Obstructive sleep apnea syndrome | 0 Participants |
| C4181001 Cohort | Number of Participants With Other Achondroplasia Related Orthopedic Complications | Otitis media | 0 Participants |
| C4181001 Cohort | Number of Participants With Other Achondroplasia Related Orthopedic Complications | Otitis media acute | 0 Participants |
| C4181001 Cohort | Number of Participants With Other Achondroplasia Related Orthopedic Complications | Obstructive sleep apnea syndrome | 0 Participants |
| C4181001 Cohort | Number of Participants With Other Achondroplasia Related Orthopedic Complications | Hydrocephalus | 2 Participants |