Continuation Study of Long-term Safety, Tolerability, Pharmacokinetics and Efficacy of Recifercept in Achondroplasia

Achondroplasia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05116046
• Other study ID #: C4181008
• Secondary ID: 2021-003149-39
• Status: Terminated
• Phase: Phase 2
• Start date: December 24, 2021
• Est. completion date: March 30, 2023

Study information

• Verified date: February 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 35
• Est. completion date: March 30, 2023
• Est. primary completion date: December 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Months to 12 Years

Eligibility

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).

Related Conditions & MeSH terms

• Achondroplasia

Intervention

Biological:
• Recifercept
Recifercept

Locations

Country	Name	City	State
Australia	Murdoch Children's Research Institute	Parkville	Victoria
Belgium	Antwerp University Hospital	Edegem
Belgium	UZ Leuven - Center of Human Genetics	Leuven	Vlaams - Gewest
Denmark	Bispebjerg Hospital	Copenhagen
Denmark	Bispebjerg Hospital	Kobenhavn
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS Università Cattolica del Sacro Cuore	Roma
Portugal	Centro Hospitalar e Universitário de Coimbra - Hospital Pediátrico	Coimbra
Spain	Hospital Vithas San Jose	Vitoria - Gasteiz	Alava
United States	Texas Childrens Hospital/Baylor College of Medicine	Houston	Texas
United States	Ocean Sleep Medicine	Irvine	California
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	MemorialCare Sleep Disorders Center at Long Beach Memorial Medical Center	Long Beach	California
United States	Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center	Torrance	California
United States	Nemours Children's Hospital, Delaware	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Denmark,  Italy,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Severe AEs	An AE was any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. TEAE was an AE that occurred after initiation of study treatment that was not present at the time of treatment start or an AE that increased in severity after the initiation of medication, if the event was present at the time of treatment start emerges. SAE was an AE resulting in any of the following outcomes or considered medically significant: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or birth defect. Severe AEs were AEs that were medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated disabling, limiting self-care activities of daily living.	From first dose of study drug up to 28 days after last dose of study drug (maximum up to 11 months)
Primary	Change From Baseline in Height at Month 24	Height was measured using anthropometric measurements. Anthropometric data was collected by appropriately trained individuals at the trial site and in accordance with the anthropometric measurement manual.	Baseline, Month 24
Secondary	Clearance (CL/F) of Recifercept	Clearance of a drug was a measure of the rate at which a drug is metabolised or eliminated by normal biological processes.	Predose on Day 91, 181, 271, 361 and 451.
Secondary	Change From Baseline in Sitting Height to Standing Height Ratio at Months 3, 6, 9	Sitting height to standing height ratio was calculated based upon the anthropometric measurements. Anthropometric data was collected by appropriately trained individuals at the trial site and in accordance with the anthropometric measurement manual.	Baseline and Months 3, 6, 9
Secondary	Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9	Height and length difference was calculated with anthropometric measurements. Anthropometric data was collected by appropriately trained individuals at the trial site and in accordance with the anthropometric measurement manual.	Baseline and Months 3, 6, 9
Secondary	Change From Baseline in Knee Height to Lower Segment Ratio at Months 3, 6, 9	Knee height was defined as the distance from the sole of the foot to the most anterior surface of the femoral condyles of the thigh (medial being more anterior), with the ankle and knee each flexed to a 90-degree angle. Lower segment of the leg included tibia and foot height	Baseline and Months 3, 6, 9
Secondary	Change From Baseline in Occipito-Frontal Circumference at Months 3, 6, 9	Occipito-frontal circumference was measured by anthropometric measurements. It was measured over the most prominent part on the back of the head (occiput) and just above the eyebrows (supraorbital ridges).	Baseline and Months 3, 6, 9
Secondary	Change From Baseline in Occipito-Frontal Distance to Occipito-mid-Face Measurements Ratio at Months 3, 6, 9	Occipito-frontal circumference was measured by anthropometric measurements. Anthropometric data was collected by appropriately trained individuals at the trial site and in accordance with the anthropometric measurement manual.	Baseline, Months 3, 6, 9
Secondary	Change From Baseline in Z-Score for Occipito-frontal Circumference, Arm Span, Sitting Height and Skull Morphology at Months 3, 6, 9	The Z-score described how many standard deviations a given measurement lies above or below a size or age-specific population mean. A Z-score above the population mean indicates a positive value, whereas a Z-score below the population mean indicates a negative value. The greater the deviation of the Z-score from zero (in a positive or negative direction), the greater the magnitude of deviation from the mean.	Baseline, Months 3, 6, 9
Secondary	Change From Baseline in Fixed Flexion Angles at Elbow at Months 3, 6, 9	Fixed Flexion Angles was measured by anthropometric measurements. Anthropometric data was collected by appropriately trained individuals at the trial site and in accordance with the anthropometric measurement manual.	Baseline, Months 3, 6, 9
Secondary	Change From Baseline in Body Mass Index (BMI) at Months 3, 6, 9		Baseline, Months 3, 6, 9
Secondary	Change From Baseline in Waist to Chest Circumference Ratio at Months 3, 6, 9		Baseline, Months 3, 6, 9
Secondary	Number of Participants With Clinically Meaningful Findings in Laboratory Test Parameters Through the Study	Laboratory parameters that were assessed included lymphocytes, neutrophils, eosinophils, monocytes and potassium. Clinically significant abnormal laboratory findings were determined based on investigator's decision.	From baseline up to end of study/early termination (for a maximum duration of 11 months)
Secondary	Number of Participants With Clinically Significant Findings in Vital Signs Through the Study	Absolute values and changes from baseline in supine systolic and diastolic blood pressure, oral temperature, and pulse rate were planned to be summarized by treatment in accordance with the sponsor reporting standards. Clinically significant abnormal laboratory findings were those which were not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.	From baseline up to end of study/early termination (for a maximum duration of 11 months)
Secondary	Number of Participants With Clinically Significant Findings in Physical Examination Through the Study	A complete physical examination included cardiovascular, respiratory, gastrointestinal systems, and skin. Height and weight will also be measured and recorded as part of the anthropometric measurements collected. Anthropometric data was collected by appropriately trained individuals at the trial site and in accordance with the anthropometric measurement manual.	From baseline up to end of study/early termination (for a maximum duration of 11 months)
Secondary	Number of Participants With Positive Anti-Drug Antibodies (ADA)		From Month 3 up to end of study/early termination (up to Month 11)

External Links

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