A Research Study of How Well Macimorelin Works to Find Out if Children Have a Lack of Growth Hormone and How Safe it is
- Conditions
- Growth Hormone Deficiency
- Interventions
- Registration Number
- NCT04786873
- Lead Sponsor
- AEterna Zentaris
- Brief Summary
This research study will find out if a new growth hormone stimulation test is safe and works as well as other tests to diagnose growth hormone deficiency (GHD) in children. The stimulation test will use a new growth hormone stimulating substance called macimorelin. By now, only adults in the USA can get this new stimulation test. The results of this study are expected to help children and teenagers with suspected GHD to get the macimorelin stimulation test.
The macimorelin test will be compared to a clonidine and an arginine test. Both are known standard stimulation tests. Altogether two macimorelin tests are planned to be performed in the study, to show how repeatable macimorelin tests results are (under a set of similar conditions).
- Detailed Description
Each study participant (patient) will have 5 to 6 visits in total with the study doctor.
The study will last for about 1 to 4 months, dependent on how close the visits are done. At the visits 2, 3, 4 and 5, the patient will get a stimulation test done and blood samples will be taken. At those 4 visits, the patient will have either to drink a macimorelin drink, take some clonidine tablets or get an arginine infusion. In total, the patient will get 2 macimorelin, 1 clonidine and 1 arginine test done. The level of growth hormone (GH) will be measured 4 times during the clonidine and during the arginine test and 5 times during the macimorelin test. After the test, questions on the test tolerability will be captured from patients and parents. After the arginine test, a urine dipstick test is to be done by the patient at home.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 101
- Informed consent of subject, parent(s) or legally acceptable representative (LAR) of subject and child assent, if appropriate, must be obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
- Male and female pediatric subjects from 2 to less than 18 years of age at the time of signing informed consent.
- Indication for the performance of growth hormone stimulation test.
- Presence of a height measurement minimum 6 and maximum 18 months prior to screening.
- Established diagnosis of a disease that is sufficient to explain growth deficiency or metabolic disorders that are also associated with short stature (e.g., Turner syndrome, skeletal dysplasia's, celiac disease, etc.).
- Ongoing growth hormone therapy.
- Presence of hypothyroidism and/or adrenal insufficiency without adequate and stable replacement therapy treatment for at least 30 days prior to first GHST.
- Treatment with drugs directly affecting the pituitary secretion of somatotropin (e.g., somatostatin analogues, clonidine, levodopa and dopamine agonists) or provoking the release of somatostatin (antimuscarinic agents e.g., atropine).
- Medical history of ongoing clinically symptomatic psychiatric disorders.
- 2nd or 3rd degree atrioventricular-block, prolongation of the QRS complex over 120 milliseconds, prolongation of the QTc interval over 450 milliseconds, or any other clinically significant abnormal electrocardiogram results at the V2 pre-dose electrocardiogram (ECG) as judged by the investigator.
- Previous participation in this trial. Participation is defined as signed informed consent.
- Participation in any clinical trial of an approved or non-approved investigational medicinal product within 30 days before screening.
- Known or suspected hypersensitivity to trial product(s) or related products;
- Any disorder, which in the investigator's opinion might jeopardize subject's safety or compliance with the protocol.
- Concomitant treatment with any drugs that might prolong QT/QTc Note: A subject who receives such treatment will not be a candidate for this study, if his/her condition does not allow for a treatment-free period of at least 5 elimination half-lives of the drug that might prolong QT/QTc before the GHST;
- Elevation of laboratory parameters indicating hepatic or renal dysfunction or damage (aspartate amino transferase (AST), alkaline phosphatase (ALT), gamma-glutamyl transferase (GGT) > 2.5 x upper limit of normal (ULN); creatinine or bilirubin > 1.5x ULN);
- Current active malignancy other than non-melanoma skin cancer;
- Female of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice).
- Male of reproductive age who or whose partner(s) is not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice).
- Lack of ability or willingness to give informed consent by the subject and/or his/her legal representative;
- Anticipated non-availability for trial visits/procedures.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description standard GHST order randomized: arginine - clonidine Arginine At visit 2 (V2), all subjects will perform the macimorelin GHST and will be randomized 1:1 to the order of the clonidine and arginine GHSTs at visit 3 (V3) and visit 4 (V4). In this arm, those subjects will be presented which will have been randomized to the arginine GHST at V3 and the clonidine GHST at V4. At visit 5 (V5) all subjects will perform the macimorelin GHST. standard GHST order randomized: arginine - clonidine Clonidine At visit 2 (V2), all subjects will perform the macimorelin GHST and will be randomized 1:1 to the order of the clonidine and arginine GHSTs at visit 3 (V3) and visit 4 (V4). In this arm, those subjects will be presented which will have been randomized to the arginine GHST at V3 and the clonidine GHST at V4. At visit 5 (V5) all subjects will perform the macimorelin GHST. standard GHST order randomized: clonidine - arginine Arginine At V2, all subjects will perform the macimorelin GHST and will be randomized 1:1 to the order of the clonidine and arginine GHSTs at V3 and V4. In this arm, those subjects will be presented which will have been randomized to the clonidine GHST at V3 and to the arginine GHST at V4. At V5 all subjects will perform the macimorelin GHST. standard GHST order randomized: clonidine - arginine Clonidine At V2, all subjects will perform the macimorelin GHST and will be randomized 1:1 to the order of the clonidine and arginine GHSTs at V3 and V4. In this arm, those subjects will be presented which will have been randomized to the clonidine GHST at V3 and to the arginine GHST at V4. At V5 all subjects will perform the macimorelin GHST. standard GHST order randomized: clonidine - arginine Macimorelin At V2, all subjects will perform the macimorelin GHST and will be randomized 1:1 to the order of the clonidine and arginine GHSTs at V3 and V4. In this arm, those subjects will be presented which will have been randomized to the clonidine GHST at V3 and to the arginine GHST at V4. At V5 all subjects will perform the macimorelin GHST. standard GHST order randomized: arginine - clonidine Macimorelin At visit 2 (V2), all subjects will perform the macimorelin GHST and will be randomized 1:1 to the order of the clonidine and arginine GHSTs at visit 3 (V3) and visit 4 (V4). In this arm, those subjects will be presented which will have been randomized to the arginine GHST at V3 and the clonidine GHST at V4. At visit 5 (V5) all subjects will perform the macimorelin GHST.
- Primary Outcome Measures
Name Time Method Area under the Receiver Operator Characteristic curve (ROC AUC) based on GH concentration during GHST following macimorelin administration Derived from Cmax GH measurements collected in the time frame from 0 to 90 minutes after initial macimorelin GHST (visit 2 (day 0)) and GH adjudication status performed by the adjudication committee after visit 4 (between day 11 and day 58)). Assuming the outcome of GHD status adjudication final clinical diagnosis as the "true" GHD status, the diagnostic efficacy (estimated sensitivity, specificity, misclassification) of the macimorelin GHST will be based on the area under the receiver operating characteristic curve (ROC AUC).
- Secondary Outcome Measures
Name Time Method Sensitivity for the macimorelin GHST Derived from Cmax GH measurements collected in the time frame from 0 to 90 minutes after initial macimorelin GHST (visit 2 (day 0)) and GH adjudication status performed by the adjudication committee after visit 4 (between day 11 and day 58)). Sensitivity (confirmatory secondary endpoint) will be derived from the empirical ROC plot using this GH cut-off point.
Specificity for the macimorelin GHST Derived from Cmax GH measurements collected in the time frame from 0 to 90 minutes after initial macimorelin GHST (visit 2 (day 0)) and GH adjudication status performed by the adjudication committee after visit 4 (between day 11 and day 58)). Specificity (confirmatory secondary endpoint) will be derived from the empirical ROC plot using this GH cut-off point.
Overall agreement between the outcome of the macimorelin GHST and the combined outcome from the 2 standard GHSTs Visit 4 (between day 11 and day 58) Agreement between the outcome of macimorelin and the combined outcome of the 2 standard GHSTs will be evaluated by 'percent overall agreement'.
Trial Locations
- Locations (45)
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
🇵🇱Wrocław, Poland
Emory Healthcare-Children's Center
🇺🇸Atlanta, Georgia, United States
Evangelisches Klinikum Bethel
🇩🇪Bielefeld, Germany
MED-POLONIA Sp.z o.o.
🇵🇱Poznań, Poland
Kliniczny Szpital Wojewodzki nr 2 im. Sw. Jadwigi Krolowej w Rzeszowie
🇵🇱Rzeszów, Poland
Pediatric Endocrine Associates, p.c.
🇺🇸Greenwood Village, Colorado, United States
Osp. dei Bambini V. Buzzi, ASST Fatebenefratelli Sacco
🇮🇹Milano, Italy
IRCCS Ospedale Pediatrico Bambino Gesù
🇮🇹Roma, Italy
Kocaeli University Faculty of Medicine
🇹🇷Kocaeli, Turkey
National Institute of Endocrinology and Diabetology
🇸🇰Ľubochňa, Slovakia
Ospedale Pediatrico G. Salesi
🇮🇹Ancona, Italy
Azienda Ospedaliero-Universitaria di Parma Ospedale dei Bambini Pietro Barilla, Clinica Pediatrica
🇮🇹Parma, Italy
John Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
National Institute of Children's Diseases
🇸🇰Bratislava, Slovakia
Karadeniz Technical University
🇹🇷Ortahisar, Turkey
Clinical Center Nis - Clinic for Children's Internal Medicine
🇷🇸Niš, Serbia
Yerevan State Medical University after Mkhitar Heraci
🇦🇲Yerevan, Armenia
Spitalul Clinic Judetean Mures
🇷🇴Târgu-Mureş, Romania
St. Luke's Children's Endocrinology
🇺🇸Boise, Idaho, United States
University of Minnesota, Masonic Children's Hospital
🇺🇸Minneapolis, Minnesota, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Angel Wing Clinic For Children With Diabetes
🇺🇸Tucson, Arizona, United States
The Children's Mercy Hospital - Broadway
🇺🇸Kansas City, Missouri, United States
Alchemi Research Center
🇺🇸Rosharon, Texas, United States
Children's Hospital at Montefiore
🇺🇸Bronx, New York, United States
UNC Hospitals
🇺🇸Chapel Hill, North Carolina, United States
Multicare Health System
🇺🇸Tacoma, Washington, United States
TSMU Givi Jvania Pediatric Academic Clinik
🇬🇪Tbilisi, Georgia
National Institute of Endocrinology
🇬🇪Tbilisi, Georgia
SPSK Nr 1 im. prof. Tadeusza Sokolowskiego PUM
🇵🇱Szczecin, Poland
Azienda Ospedaliero-Universitaria Anna Meyer
🇮🇹Firenze, Italy
Cen Med de Diagn si Trat Amb NEOMED
🇷🇴Braşov, Romania
Institutul de Endocrinologie "C.I. Parhon"
🇷🇴Bucharest, Romania
Sana Monitoring
🇷🇴Bucuresti, Romania
Spitalul Cl. de Urgenta pentru Copii Louis Turcanu Timisoara
🇷🇴Timişoara, Romania
Medicover Hospitals
🇷🇴Bucuresti, Romania
Spitalul Clinic Judetean de Urgenta "Sf. Spiridon" Iasi
🇷🇴Iaşi, Romania
University children's clinic Belgrade - Department of Endocrinology
🇷🇸Belgrade, Serbia
Children's University Hospital Kosice
🇸🇰Košice, Slovakia
Univerzitetni Klinicni Center Ljubljana - Pediatrics
🇸🇮Ljubljana, Slovenia
Ankara University, Faculty of Medicine
🇹🇷Ankara, Turkey
Antalya Training and Research Hospital
🇹🇷Antalya, Turkey
JSC Maritime Hospital
🇬🇪Batumi, Georgia
Spitalul Clinic Judetean de Urgenta "Sf. Apostol Andrei" Constanta
🇷🇴Constanţa, Romania
Institute for Child and Youth Health Care of Vojvodina - Endocrinology
🇷🇸Novi Sad, Serbia