ASCEND-Peds
A Phase 1/2, Multi-Center, Open-Label, Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Exploratory Efficacy of Olipudase Alfa in Pediatric Patients Aged <18 Years With Acid Sphingomyelinase Deficiency
Sponsor study identifier
Secondary identifiers
OTHER · UTN
interventional
20
6 countries
6
Study Start
May 1, 2015
Actual (reported)Primary Completion
December 9, 2019
Actual (reported)Study Completion
December 9, 2019
Actual (reported)Primary Objective: To evaluate the safety and tolerability of olipudase alfa administered intravenously in pediatric participants every 2 weeks for 64 weeks. Secondary Objective: To characterize the pharmacokinetic profile and evaluate the pharmacodynamics and exploratory efficacy of olipudase alfa administered intravenously in pediatric participants every 2 weeks for 64 weeks.
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
December 9, 2019
Actual (reported)Click on a node to explore related trials.
Some registry-reported names shown below are not yet linked in this graph.
Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
November 7, 2014
Actual (reported)November 17, 2014
Actual (reported)May 1, 2015
Actual (reported)December 9, 2019
Actual (reported)December 9, 2019
Actual (reported)February 1, 2021
Actual (reported)Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAEs were defined as adverse events (AEs) that occurred or worsened during the on-treatment period (time from the start of investigational medicinal product \[IMP\]) administration until end of study (i.e. up to 64 weeks).
From Baseline up to End of study (64 weeks)
Number of Participants With Infusion-Associated Reactions (IARs)
IARs were defined as AEs that occurred during the infusion or within up to 24 hours after the start of infusion and were considered as related or possibly related to the study treatment by the investigator or the sponsor. Protocol-defined IAR: all AEs that were identified as an IAR by the investigator. Events occurring greater than or equal to (\>=) 24 hours after the start of an infusion might had been judged an IAR at the discretion of the investigator or sponsor.
Within up to 24 hours after start of any infusion (during the treatment period i.e. from Baseline up to 64 weeks)
Number of Participants With Change in Physical Examination
Change from Normal assessment (at Baseline) to Abnormal assessment (at Week 52) was reported. Physical examinations included following observations/measurements: examination of the skin, head, eyes, ears, nose, and throat; lymph nodes; heart, lungs, and abdomen; extremities and joints. Abnormality in physical examinations was based on investigator's discretion.
Baseline, Week 52 (last complete assessment)
Number of Participants With Change in Neurological Examination
Change from Normal assessment (at Baseline) to Abnormal assessment (at Week 52) was reported. Neurological examination included: coordination examination, cranial nerve examination, extrapyramidal features, fundoscopy, gait and coordination examination, motor examination, tone peripheral nervous system, reflexes examination, sensory examination, strength examination, mental status.
Baseline, Week 52 (last assessment)
Number of Participants With Abnormal Liver Function Laboratory Values at the End of Study
Abnormal values in alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and alkaline phosphatase were reported.
At End of Study (Week 64)
Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities
* Heart Rate (HR) High: \>=120 beats per minute (bpm) (adolescents), \>=120 bpm (children), \>=140 bpm (early children), \>=175 bpm (infants) \& increase from baseline (IFB) \>=20 bpm for all age categories. * HR Low: \<=50 bpm (adolescents), \<=50 bpm (children), \<=75 bpm (early children), \<=80 bpm (infants) \& decrease from baseline (DFB) \>=20 bpm for all age categories. * Systolic BP (SBP) High: \>=119 mmHg (adolescents), 108 mmHg (children), 101 mmHg (in early children), 98 mmHg (infants) \& IFB \>=20 mmHg for all age categories. * SBP Low: \<=90 mmHg (adolescents), \<= 80mm Hg (children), \<=70 mmHg (early children), \<=70 mmHg (infants) \& DFB \>=20 mmHg for all age categories. * Diastolic BP (DBP) High:\>=78 mmHg (adolescents), \>=72 mmHg (children), \>=59 mmHg (in early children), \>=54 mmHg (infants) \& IFB \>=10 mmHg for all age categories. * DBP Low:\<=54 mmHg (adolescents), \<=48 mmHg (children), \<=34 mmHg (early children), \<=34 mmHg (infants) \& DFB \>=10 mmHg for all age categories.
From Baseline up to End of Study (64 weeks)
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities
Criteria for potentially clinically significant ECG abnormalities: * High PR Interval: \>=180 milliseconds (ms) in adolescents, 170 ms in children, 160 ms in early children, and 140 ms in infants; * High QRS Interval: \>=110 ms in adolescents, 100 ms in children, 95 ms in early children and 85 ms in infants; * Prolonged QTc Fridericia (QTc F): \>450 ms in male adolescents, children, early children and infants or 470 ms in female adolescents, * QTc F \>500 ms; * QTc F increase from baseline \>60 ms.
From Baseline up to End of Study (64 weeks)
Change From Baseline in Safety Biomarker Level: High Sensitivity C Reactive Protein (hsCRP) at Week 64
Baseline, Week 64 (pre-infusion)
Change From Baseline in Safety Biomarker: Ceramide Level at Week 64
Baseline, Week 64 (pre-infusion)
Change From Baseline in Safety Biomarker: Iron at Week 64
Baseline, Week 64 (pre-infusion)
Change From Baseline in Safety Biomarker: Cardiac Troponin I and Ferritin at Week 64
Baseline, Week 64 (pre-infusion)
Change From Baseline in Safety Biomarker: Interleukin (IL)-6 and IL-8 at Week 24
Baseline, Week 24 (pre-infusion, last assessment)
Change From Baseline in Safety Biomarker: Calcitonin at Week 64
Baseline, Week 64 (pre-infusion)
Doppler Echocardiogram: Absolute Change From Baseline in Left Ventricular Ejection Fraction at Week 52
Baseline, Week 52 (last assessment)
Number of Participants With Treatment-Emergent Antibody: Treatment-Induced/Treatment-Boosted Anti-drug Antibodies and Neutralizing Antibody (NAb)
Serum samples for immunogenicity assessment were analyzed to detect ADA. ADA response were categorized as: treatment emergent antibody i.e. treatment-induced/treatment-boosted response. A participant whose ADA status was positive anytime post-baseline and was negative or missing at baseline was considered to have treatment induced ADA. A participant whose ADA status was positive at baseline (pre-existing ADA) and the ADA titer level anytime post-baseline was significantly higher than that at baseline is considered to have treatment boosted ADA. Positive samples in the ADA assay were further analyzed in the NAb assay as positive NAb inhibition of catalytic activity and positive NAb inhibition of cellular uptake.
From Baseline up to Week 64
Number of Participants With Abnormalities in Liver Ultrasound Doppler at Week 52
Evidence of portal hypertension was assessed by portal vein direction from liver ultrasound doppler.
Week 52 (last assessment)
Pharmacokinetic (PK) Parameter: Plasma Concentration of Olipudase Alfa at the End of Infusion (Ceoi)
At the end of infusion of the first 3.0 mg/kg dose and at Week 52
Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) of Olipudase Alfa
Adolescent: at pre-infusion, EOI, 2 h, 6 h, 24 h, 48 h & 72 h (at first 3.0 mg/kg dose) or 96 h (at Week 52) post EOI; Child & infant/early child: pre-infusion, 0-30 min, 2-4 h, 6-12 h, 24-36 h, and 84-96 h post EOI at the first 3.0 mg/kg dose & Week 52
Pharmacokinetic Parameter: AUC0-last, AUC(0-tau) of Olipudase Alfa
Adolescent: at pre-infusion, EOI, 2 h, 6 h, 24 h, 48 h & 72 h (at first 3.0 mg/kg dose) or 96 h (at Week 52) post EOI; Child & infant/early child: pre-infusion, 0-30 min, 2-4 h, 6-12 h, 24-36 h, and 84-96 h post EOI at the first 3.0 mg/kg dose & Week 52
Pharmacokinetic Parameter: Terminal Half-Life of Olipudase Alfa
Adolescent: at pre-infusion, EOI, 2 h, 6 h, 24 h, 48 h & 72 h (at first 3.0 mg/kg dose) or 96 h (at Week 52) post EOI; Child & infant/early child: pre-infusion, 0-30 min, 2-4 h, 6-12 h, 24-36 h, and 84-96 h post EOI at the first 3.0 mg/kg dose & Week 52
Pharmacokinetic Parameter: Total Body Clearance (CL) of Olipudase Alfa
Participants received intravenous (IV) infusion of olipudase alfa once every 2 weeks (Q2W) for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 milligram per kilogram (mg/kg). Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
Pharmaceutical form: powder for concentrate for solution for infusion Route of administration: intravenous infusion
Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.
Investigational Site Number 840001
New York, New York, 10029, United States
Investigational Site Number 076001
Porto Alegre, 90035 003, Brazil
Investigational Site Number 250002
Bron, 69677, France
Investigational Site Number 276001
Mainz, 55131, Germany
Investigational Site Number 380001
Udine, 33100, Italy
Investigational Site Number 826001
Manchester, M13 9WL, United Kingdom
Diaz GA, Jones SA, Scarpa M, Mengel KE, Giugliani R, Guffon N, Batsu I, Fraser PA, Li J, Zhang Q, Ortemann-Renon C. One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency. Genet Med. 2021 Aug;23(8):1543-1550. doi: 10.1038/s41436-021-01156-3. Epub 2021 Apr 19.
Clinical Sciences & Operations
Sanofi
20 participants (actual enrollment reported by the registry).
First Submitted
November 7, 2014
First Posted
November 17, 2014
Study Start
May 1, 2015
Actual (reported)Adolescent: at pre-infusion, EOI, 2 h, 6 h, 24 h, 48 h & 72 h (at first 3.0 mg/kg dose) or 96 h (at Week 52) post EOI; Child & infant/early child: pre-infusion, 0-30 min, 2-4 h, 6-12 h, 24-36 h, and 84-96 h post EOI at the first 3.0 mg/kg dose & Week 52
Contact the study team to confirm eligibility.
Primary Completion
December 9, 2019
Actual (reported)Study Completion
December 9, 2019
Actual (reported)Last Updated
March 23, 2022
Results First Posted
February 1, 2021
Record last verified: 2022-03
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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Source: ClinicalTrials.gov.
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