Back to resultsContinuation Study of Long-term Safety, Tolerability, Pharmacokinetics and Efficacy of Recifercept in Achondroplasia
Primary Purpose
Achondroplasia
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Recifercept
Sponsored by
About this trial
This is an interventional treatment trial for Achondroplasia focused on measuring achondroplasia, dwarfism, bone diseases, development, bone diseases, Musculoskeletal Diseases, Osteochondrodysplasias, Genetic Diseases, Inborn, Skeletal Dysplasia
Eligibility Criteria
Inclusion Criteria:
- Male and female participants between the ages of >15 months to <12 years inclusive, at Visit 1 (Screen 1).
- Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests lifestyle considerations and other study procedures.
- Completed the C4181005 Phase 2 study.
- Able to stand independently for height measurements (if ≥2 years of age at enrollment).
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 (body mass index (BMI) >95th percentile on Hoover-Fong BMI charts) [Hoover-Fong et al, 2008].
- Known closure of long bone growth plates (cessation of height growth).
- Body weight >45 kg.
- 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 beclometasone 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 other (except recifercept) investigational product for achondroplasia or that may affect growth/interpretation of growth parameters.
- History of receipt of an investigational drug (not for achondroplasia/growth affecting) within the last 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
Sites / Locations
- Ocean Sleep Medicine
- Long Beach Memorial Medical Center
- MemorialCare Sleep Disorders Center at Long Beach Memorial Medical Center
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Nemours Children's Hospital, Delaware
- Texas Childrens Hospital/Baylor College of Medicine
- Murdoch Children's Research Institute
- UZ Leuven - Center of Human Genetics
- Antwerp University Hospital
- Bispebjerg Hospital
- Bispebjerg Hospital
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS Università Cattolica del Sacro Cuore
- Centro Hospitalar e Universitário de Coimbra - Hospital Pediátrico
- Hospital Vithas San Jose
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Low Dose
Medium Dose
High Dose
Arm Description
Low Dose
Medium Dose
High Dose
Outcomes
Primary Outcome Measures
Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
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 24 months 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.
Height
Increase in height growth above expected in reference population
Secondary Outcome Measures
Pharmacokinetics - Apparent Clearance (CL/F)
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.
Change from Baseline in Standing & Sitting Height
Sitting height/standing height ratio
Change from Baseline in Arm Span
Arm span to height/length difference
Change from Baseline in Lower Leg Length
Knee height:lower segment ratio
Change from Baseline in Cranial Face Measurements
Occipito-frontal circumference
Change from Baseline in Cranial Face Measurements
Ratio of occipito-frontal distance to occipito-mid-face measurements
Change from Baseline in Height
z-score of the above height to arm span proportionality and skull morphology where achondroplasia reference datasets exist
Change from Baseline in Elbow Range of Motion
Fixed flexion angles at elbow
Change from Baseline in Polysomnography
Apnea-hypopnea index (obstructive and total)
Change from Baseline in Polysomnography
Desaturation index (number of desaturations per hour >3% from baseline)
Change from Baseline in Polysomnography
Percentage time spent <90% oxygen saturation (SaO2)
Change from Baseline in Polysomnography
Percentage time spent with end-tidal carbon dioxide >50 mmHg
Change from Baseline in Polysomnography
SaO2 nadir
Change from Baseline in Body Mass Index
Body mass index (BMI)
Change from Baseline in Waist & Chest Circumference
Waist:chest circumference ratio
Number of Participants With Laboratory Abnormalities
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)
Number of Participants With Change From Baseline in Vital Signs
Following parameters were analyzed for examination of vital signs: systolic and diastolic blood pressure, respiratory rate, radial pulse and body temperature.
Number of Participants With Change From Baseline in Physical Examination
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.
Number of Participants With Anti-Drug Antibody (ADA)
The percentage of participants with positive ADA and neutralizing antibodies will be summarized for each treatment arm.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05116046
Brief Title
Continuation Study of Long-term Safety, Tolerability, Pharmacokinetics and Efficacy of Recifercept in Achondroplasia
Official Title
A PHASE 2 OPEN LABEL EXTENSION STUDY TO ASSESS THE LONG-TERM SAFETY, TOLERABILITY, PHARMACOKINETICS AND EFFICACY OF RECIFERCEPT IN CHILDREN WITH ACHONDROPLASIA
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated due to lack of efficacy at any of the tested doses on 18th November 2022. The decision to terminate the study is not related to a safety concern.
Study Start Date
December 24, 2021 (Actual)
Primary Completion Date
December 16, 2022 (Actual)
Study Completion Date
March 30, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
All participants who completed the prior study to assess long-term safety, tolerability, pharmacokinetics and efficacy, and in the opinion of the investigator, continue to have a positive risk:benefit profile, will be offered to enroll in this open-label extension (OLE) study for up to an additional 24 months of treatment.
Approximately 63 participants will be offered to continue at the previously received dose of Recifercept either
Low Dose Medium Dose High Dose
or at the therapeutic dose once it is identified.
Participants will attend the clinic monthly for 24 months. Assessments include safety, blood sampling, physical examination, vital signs, anthropometric body measurements & patient/caregiver quality of life questionnaires.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Achondroplasia
Keywords
achondroplasia, dwarfism, bone diseases, development, bone diseases, Musculoskeletal Diseases, Osteochondrodysplasias, Genetic Diseases, Inborn, Skeletal Dysplasia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low Dose
Arm Type
Experimental
Arm Description
Low Dose
Arm Title
Medium Dose
Arm Type
Experimental
Arm Description
Medium Dose
Arm Title
High Dose
Arm Type
Experimental
Arm Description
High Dose
Intervention Type
Biological
Intervention Name(s)
Recifercept
Intervention Description
Recifercept
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
Description
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 24 months 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.
Time Frame
Baseline (Day 0) up to 24 months after last dose of study medication
Title
Height
Description
Increase in height growth above expected in reference population
Time Frame
Change in height from baseline up to 24 months after last dose
Secondary Outcome Measure Information:
Title
Pharmacokinetics - Apparent Clearance (CL/F)
Description
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.
Time Frame
Month(s) 3, 6, 9, 12, 15, 18, 21 & 24
Title
Change from Baseline in Standing & Sitting Height
Description
Sitting height/standing height ratio
Time Frame
Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months
Title
Change from Baseline in Arm Span
Description
Arm span to height/length difference
Time Frame
Baseline, 3, 6, 9, 12, 15, 18, & 24 Months
Title
Change from Baseline in Lower Leg Length
Description
Knee height:lower segment ratio
Time Frame
Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months
Title
Change from Baseline in Cranial Face Measurements
Description
Occipito-frontal circumference
Time Frame
Baseline, 3, 6, 9, 12, 15, 18 & 24 Months
Title
Change from Baseline in Cranial Face Measurements
Description
Ratio of occipito-frontal distance to occipito-mid-face measurements
Time Frame
Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months
Title
Change from Baseline in Height
Description
z-score of the above height to arm span proportionality and skull morphology where achondroplasia reference datasets exist
Time Frame
Baseline, 3, 6, 9, 12, 15, 18, 21 & 24 Months
Title
Change from Baseline in Elbow Range of Motion
Description
Fixed flexion angles at elbow
Time Frame
Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months
Title
Change from Baseline in Polysomnography
Description
Apnea-hypopnea index (obstructive and total)
Time Frame
Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months
Title
Change from Baseline in Polysomnography
Description
Desaturation index (number of desaturations per hour >3% from baseline)
Time Frame
Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months
Title
Change from Baseline in Polysomnography
Description
Percentage time spent <90% oxygen saturation (SaO2)
Time Frame
Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months
Title
Change from Baseline in Polysomnography
Description
Percentage time spent with end-tidal carbon dioxide >50 mmHg
Time Frame
Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months
Title
Change from Baseline in Polysomnography
Description
SaO2 nadir
Time Frame
Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months
Title
Change from Baseline in Body Mass Index
Description
Body mass index (BMI)
Time Frame
Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months
Title
Change from Baseline in Waist & Chest Circumference
Description
Waist:chest circumference ratio
Time Frame
Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months
Title
Number of Participants With Laboratory Abnormalities
Description
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)
Time Frame
Baseline up to end of treatment (24 months)
Title
Number of Participants With Change From Baseline in Vital Signs
Description
Following parameters were analyzed for examination of vital signs: systolic and diastolic blood pressure, respiratory rate, radial pulse and body temperature.
Time Frame
Baseline up to end of treatment (24 months)
Title
Number of Participants With Change From Baseline in Physical Examination
Description
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.
Time Frame
Baseline up to end of treatment (24 months)
Title
Number of Participants With Anti-Drug Antibody (ADA)
Description
The percentage of participants with positive ADA and neutralizing antibodies will be summarized for each treatment arm.
Time Frame
Baseline up to end of treatment (24 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
15 Months
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and female participants between the ages of >15 months to <12 years inclusive, at Visit 1 (Screen 1).
Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests lifestyle considerations and other study procedures.
Completed the C4181005 Phase 2 study.
Able to stand independently for height measurements (if ≥2 years of age at enrollment).
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 (body mass index (BMI) >95th percentile on Hoover-Fong BMI charts) [Hoover-Fong et al, 2008].
Known closure of long bone growth plates (cessation of height growth).
Body weight >45 kg.
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 beclometasone 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 other (except recifercept) investigational product for achondroplasia or that may affect growth/interpretation of growth parameters.
History of receipt of an investigational drug (not for achondroplasia/growth affecting) within the last 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Ocean Sleep Medicine
City
Irvine
State/Province
California
ZIP/Postal Code
92604
Country
United States
Facility Name
Long Beach Memorial Medical Center
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
MemorialCare Sleep Disorders Center at Long Beach Memorial Medical Center
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
Nemours Children's Hospital, Delaware
City
Wilmington
State/Province
Delaware
ZIP/Postal Code
19803
Country
United States
Facility Name
Texas Childrens Hospital/Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Murdoch Children's Research Institute
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
UZ Leuven - Center of Human Genetics
City
Leuven
State/Province
Vlaams - Gewest
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Antwerp University Hospital
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
Bispebjerg Hospital
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Bispebjerg Hospital
City
Kobenhavn
ZIP/Postal Code
2400
Country
Denmark
Facility Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS Università Cattolica del Sacro Cuore
City
Roma
ZIP/Postal Code
00168
Country
Italy
Facility Name
Centro Hospitalar e Universitário de Coimbra - Hospital Pediátrico
City
Coimbra
ZIP/Postal Code
3000-602
Country
Portugal
Facility Name
Hospital Vithas San Jose
City
Vitoria - Gasteiz
State/Province
Alava
ZIP/Postal Code
01008
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=C4181008
Description
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Learn more about this trial
Continuation Study of Long-term Safety, Tolerability, Pharmacokinetics and Efficacy of Recifercept in Achondroplasia
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