A PHASE 2 OPEN LABEL EXTENSION STUDY TO ASSESS THE LONG-TERM SAFETY, TOLERABILITY, PHARMACOKINETICS AND EFFICACY OF RECIFERCEPT IN CHILDREN WITH ACHONDROPLASIA
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 35
- 试验地点
- 27
- 主要终点
- Change From Baseline in Height at Month 24
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 15 Months 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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).
结局指标
主要结局
Change From Baseline in Height at Month 24
时间窗: Baseline, 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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Severe AEs
时间窗: From first dose of study drug up to 28 days after last dose of study drug (maximum up to 11 months)
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.
次要结局
- Clearance (CL/F) of Recifercept(Predose on Day 91, 181, 271, 361 and 451.)
- Change From Baseline in Occipito-Frontal Circumference at Months 3, 6, 9(Baseline and Months 3, 6, 9)
- Change From Baseline in Occipito-Frontal Distance to Occipito-mid-Face Measurements Ratio at Months 3, 6, 9(Baseline, Months 3, 6, 9)
- Change From Baseline in Body Mass Index (BMI) at Months 3, 6, 9(Baseline, Months 3, 6, 9)
- Number of Participants With Clinically Significant Findings in Physical Examination Through the Study(From baseline up to end of study/early termination (for a maximum duration of 11 months))
- Change From Baseline in Waist to Chest Circumference Ratio at Months 3, 6, 9(Baseline, Months 3, 6, 9)
- Change From Baseline in Sitting Height to Standing Height Ratio at Months 3, 6, 9(Baseline and Months 3, 6, 9)
- Change From Baseline in Arm Span to Height/Length Difference at Months 3, 6, 9(Baseline and Months 3, 6, 9)
- Number of Participants With Clinically Significant Findings in Vital Signs Through the Study(From baseline up to end of study/early termination (for a maximum duration of 11 months))
- Number of Participants With Positive Anti-Drug Antibodies (ADA)(From Month 3 up to end of study/early termination (up to Month 11))
- Number of Participants With Clinically Meaningful Findings in Laboratory Test Parameters Through the Study(From baseline up to end of study/early termination (for a maximum duration of 11 months))
- Change From Baseline in Knee Height to Lower Segment Ratio at Months 3, 6, 9(Baseline and Months 3, 6, 9)
- Change From Baseline in Fixed Flexion Angles at Elbow at Months 3, 6, 9(Baseline, Months 3, 6, 9)
- Change From Baseline in Z-Score for Occipito-frontal Circumference, Arm Span, Sitting Height and Skull Morphology at Months 3, 6, 9(Baseline, Months 3, 6, 9)