Pharmacokinetics, Safety and Efficacy of P03277 in Pediatric Patients Undergoing Central Nervous System Contrast-enhanced MRI

NCT03749252 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: GDX-44-0072018-001516-30
• Study Type: interventional
• Target: 80
• Locations: 5 countries
• Sites: 16

Brief Summary

This is a pharmacokinetics (PK), open-label, uncontrolled, multicenter phase II trial with age-staggered approach. The primary objective is to evaluate the PK profile of gadopiclenol in plasma following single IV injection of 0.05 mmol/kg body weight (BW) in pediatric population aged from 2 to 17 years undergoing CNS contrast-enhanced MRI (CNS cohort).

Conditions

Central Nervous System Indication; Pediatric Patients; Body Indication

Outcome Measures

Primary Outcomes (8)

• Elimination Half-life

  P03277 pharmacokinetic parameters in plasma were determined from the population PK model. This outcome was assessed only for the CNS cohort.

  4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours

• Total Clearance

  P03277 pharmacokinetic parameters in plasma were determined from the population PK model. This outcome was assessed only for the CNS cohort.

  4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours

• Central Volume of Distribution

  P03277 pharmacokinetic parameters in plasma were determined from the population PK model. This outcome was assessed only for the CNS cohort.

  4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours

• Peripheral Volume of Distribution

  P03277 pharmacokinetic parameters in plasma were determined from the population PK model. This outcome was assessed only for the CNS cohort.

  4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours

• Area Under the Curve

  P03277 pharmacokinetic parameters in plasma were determined from the population PK model. This outcome was assessed only for the CNS cohort.

  4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours

• Simulated Concentrations 10 Minutes Post-injection

  P03277 pharmacokinetic parameters in plasma were determined from the population PK model. This outcome was assessed only for the CNS cohort.

  10 minutes post-injection

• Simulated Concentrations 20 Minutes Post-injection

  P03277 pharmacokinetic parameters in plasma were determined from the population PK model. This outcome was assessed only for the CNS cohort.

  20 minutes post-injection

• Simulated Concentrations 30 Minutes Post-injection

  P03277 pharmacokinetic parameters in plasma were determined from the population PK model. This outcome was assessed only for the CNS cohort.

  30 minutes post-injection

Study Arms (6)

CNS Cohort 2-6 years

EXPERIMENTAL

Pediatric patients aged 2-6 years undergoing CNS contrast-enhanced MRI

Drug: P03277

CNS Cohort 7-11 years

EXPERIMENTAL

Pediatric patients aged 7-11 years undergoing CNS contrast-enhanced MRI

Drug: P03277

CNS Cohort 12-17 years

EXPERIMENTAL

Pediatric patients aged 12-17 years undergoing CNS contrast-enhanced MRI

Drug: P03277

Body Cohort 2-6 years

EXPERIMENTAL

Pediatric patients aged 2-6 years undergoing contrast-enhanced MRI of other body organs (head and neck, thorax, abdomen, pelvis or musculoskeletal system)

Drug: P03277

Body Cohort 7-11 years

EXPERIMENTAL

Pediatric patients aged 7-11 years undergoing contrast-enhanced MRI of other body organs (head and neck, thorax, abdomen, pelvis or musculoskeletal system)

Drug: P03277

Body Cohort 12-17 years

EXPERIMENTAL

Pediatric patients aged 12-17 years undergoing contrast-enhanced MRI of other body organs (head and neck, thorax, abdomen, pelvis or musculoskeletal system)

Drug: P03277

Interventions

P03277 DRUG

A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.

Also known as: gadopiclenol

Body Cohort 12-17 years; Body Cohort 2-6 years; Body Cohort 7-11 years; CNS Cohort 12-17 years; CNS Cohort 2-6 years; CNS Cohort 7-11 years

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• To be included in the study, the patient had to meet all the following criteria:
• Female or male pediatric patient aged 2 to 17 years,
• Patient with known or suspected lesion(s) scheduled to undergo routine contrast-enhanced MRI of CNS or of other organs including at least one organ among head and neck, thorax, abdomen, pelvis or musculoskeletal system (including extremities),
• Patient whose parent(s) or legal guardian having read the information, provided their consent to patient's participation in writing by dating and signing the informed consent prior to any trial related procedure being conducted,
• Patient with capacity of understanding who received age- and maturity-appropriate information and provided his/her assent to participate in the trial (as required by national regulations),
• Patient affiliated to national health insurance according to local regulatory requirements.
• Patient planned for treatment or procedure (e.g., surgery) that would prevent obtaining the required blood samples or performing other trial procedures between the screening visit and up to 1 day after gadopiclenol administration,
• Patient undergoing treatment or procedure (e.g., diuretics, clinically significant blood loss or blood transfusion) preceding or subsequent to gadopiclenol administration that would alter gadopiclenol PK parameters,
• Patient with acute or chronic renal insufficiency defined as estimated Glomerular Filtration Rate (eGFR) out of age-adjusted normal ranges (eGFR calculated with bedside Schwartz equation),
• Patients referred for MR Angiography,
• Patient with history of bleeding disorder,
• Patient with known severe liver disease,
• Patient with known cardiac disease (e.g., heart rhythm anomalies, long QT syndrome),
• Patient with any clinically significant abnormal 12-lead ECG that in the Investigator's opinion would affect the safety evaluation or place the patient at risk,
• Patient with electrolyte or fluid imbalance that at Investigator's judgment presents undue risk assessed within 1 month prior to gadopiclenol administration,

Sponsors & Collaborators

• Guerbet: lead

Study Sites (16)

MHAT Central Onco Hospital Ltd

Plovdiv, Bulgaria

Location

Acibadem City Clinic Tokuda Hospital

Sofia, Bulgaria

Location

MHAT Dr. Stoyan Kirkovich

Stara Zagora, Bulgaria

Location

Semmelweis Egyetem II. sz Gyermekgyogyaszati Klinika

Budapest, Hungary

Location

Markhot Ferenc Oktatokorhaz es Rendelointezet

Eger, Hungary

Location

B.-A.-Z. Megyei Korhaz Gyermek-Egeszsegugyi Kozpont

Miskolc, Hungary

Location

Szpital Uniwersytecki nr 1 w Bydgoszczy im. dr Jurasza, Oddział Kliniczny Chirurgii Ogólnej i Onkologicznej Dzieci i Młodzieży

Bydgoszcz, Poland

Location

Instytut Centrum Zdrowia Matki Polki

Lodz, Poland

Location

Uniwersytecki Szpital Dziecięcy w Lublinie

Lublin, Poland

Location

Klinika Chirurgii Dziecięcej

Rzeszów, Poland

Location

Instytut "Pomnik -Centrum Zdrowia Dziecka"

Warsaw, Poland

Location

Zakład Radiologii PediatrycznejSamodzielny Publ. Dziecięcy Szp. Kliniczny w Warszawie

Warsaw, Poland

Location

II. Detská klinika SZU, Detská fakultná nemocnica s poliklinikou Banská Bystrica

Banská Bystrica, Slovakia

Location

Klinika detí a dorastu JLF UK a UNM, Univerzitná nemocnica Martin

Martin, Slovakia

Location

Faculty hospital Nitra, Clinic of neonates, children and adolescents

Nitra, Slovakia

Location

Children's City Clinical Hospital

Dnipro, Ukraine

Location

Related Publications (1)

• Jurkiewicz E, Tsvetkova S, Grinberg A, Pasquiers B. Pharmacokinetics, Safety, and Efficacy of Gadopiclenol in Pediatric Patients Aged 2 to 17 Years. Invest Radiol. 2022 Aug 1;57(8):510-516. doi: 10.1097/RLI.0000000000000865. Epub 2022 Mar 2.

  PMID: 35318970 DERIVED

MeSH Terms

Interventions

gadopiclenol

Results Point of Contact

• Title: Global Head of Medical Affairs & Clinical Development
• Organization: Guerbet

jing.hao@guerbet.com

+33 (0) 1 45 91 50 00

Study Officials

• Elżbieta Jurkiewicz, MD

  Instytut Pomnik

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2018
• First Posted: November 21, 2018
• Study Start: November 6, 2018
• Primary Completion: December 18, 2019
• Study Completion: August 10, 2020
• Last Updated: June 1, 2022
• Results First Posted: June 1, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

BU (3); PL (6); HU (3); SL (3); UA (1)