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

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05116046

Collaborator

(none)

Enrollment

Locations

Arms

71.8

Anticipated Duration (Months)

4.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Achondroplasia	Biological: Recifercept	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

63 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 24, 2021

Anticipated Primary Completion Date :

Dec 18, 2027

Anticipated Study Completion Date :

Dec 18, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Low Dose Low Dose	Biological: Recifercept Recifercept
Experimental: Medium Dose Medium Dose	Biological: Recifercept Recifercept
Experimental: High Dose High Dose	Biological: Recifercept Recifercept

Arm

Intervention/Treatment

Experimental: Low Dose

Low Dose

Biological: Recifercept

Recifercept

Experimental: Medium Dose

Medium Dose

Biological: Recifercept

Recifercept

Experimental: High Dose

High Dose

Biological: Recifercept

Recifercept

Outcome Measures

Primary Outcome Measures

Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) [Baseline (Day 0) up to 24 months after last dose of study medication]
Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 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 [Change in height from baseline up to 24 months after last dose]
Increase in height growth above expected in reference population

Secondary Outcome Measures

Pharmacokinetics - Apparent Clearance (CL/F) [Month(s) 3, 6, 9, 12, 15, 18, 21 & 24]
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 [Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months]
Sitting height/standing height ratio
Change from Baseline in Arm Span [Baseline, 3, 6, 9, 12, 15, 18, & 24 Months]
Arm span to height/length difference
Change from Baseline in Lower Leg Length [Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months]
Knee height:lower segment ratio
Change from Baseline in Cranial Face Measurements [Baseline, 3, 6, 9, 12, 15, 18 & 24 Months]
Occipito-frontal circumference
Change from Baseline in Cranial Face Measurements [Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months]
Ratio of occipito-frontal distance to occipito-mid-face measurements
Change from Baseline in Height [Baseline, 3, 6, 9, 12, 15, 18, 21 & 24 Months]
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 [Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months]
Fixed flexion angles at elbow
Change from Baseline in Polysomnography [Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months]
Apnea-hypopnea index (obstructive and total)
Change from Baseline in Polysomnography [Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months]
Desaturation index (number of desaturations per hour >3% from baseline)
Change from Baseline in Polysomnography [Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months]
Percentage time spent <90% oxygen saturation (SaO2)
Change from Baseline in Polysomnography [Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months]
Percentage time spent with end-tidal carbon dioxide >50 mmHg
Change from Baseline in Polysomnography [Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months]
SaO2 nadir
Change from Baseline in Body Mass Index [Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months]
Body mass index (BMI)
Change from Baseline in Waist & Chest Circumference [Baseline, 3, 6, 9, 12, 15, 18, 21, & 24 Months]
Waist:chest circumference ratio
Number of Participants With Laboratory Abnormalities [Baseline up to end of treatment (24 months)]
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 [Baseline up to end of treatment (24 months)]
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 [Baseline up to end of treatment (24 months)]
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) [Baseline up to end of treatment (24 months)]
The percentage of participants with positive ADA and neutralizing antibodies will be summarized for each treatment arm.

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Months to 12 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ocean Sleep Medicine	Irvine	California	United States	92604
2	Long Beach Memorial Medical Center	Long Beach	California	United States	90806
3	MemorialCare Sleep Disorders Center at Long Beach Memorial Medical Center	Long Beach	California	United States	90806
4	Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center	Torrance	California	United States	90502
5	Nemours Children's Hospital, Delaware	Wilmington	Delaware	United States	19803
6	Texas Childrens Hospital/Baylor College of Medicine	Houston	Texas	United States	77030
7	Murdoch Children's Research Institute	Parkville	Victoria	Australia	3052
8	Antwerp University Hospital	Edegem		Belgium	2650
9	Bispebjerg Hospital	Copenhagen		Denmark	2100
10	Bispebjerg Hospital	Kobenhavn		Denmark	2400
11	Fondazione Policlinico Universitario Agostino Gemelli IRCCS Università Cattolica del Sacro Cuore	Roma		Italy	00168
12	Centro Hospitalar e Universitário de Coimbra - Hospital Pediátrico	Coimbra		Portugal	3000-602
13	Hospital Vithas San Jose	Vitoria - Gasteiz	Alava	Spain	01008