Clinical trial NCT04786873: A Research Study of How Well Macimorelin Works to Find Out if Children Have a Lack of Growth Hormone and How Safe it is
Official title: Multicenter, Open Label Trial to Investigate the Efficacy and Safety of a Single Oral Dose of 1.0 mg/kg Macimorelin Acetate as Growth Hormone Stimulation Test (GHST) in Pediatric Patients With Suspected Growth Hormone Deficiency (GHD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Growth Hormone Deficiency
Keywords: childhood-onset growth hormone deficiency
diagnosis of growth hormone deficiency
diagnosis of childhood-onset growth hormone deficiency
diagnostic test for growth hormone deficiency
Lead sponsor: AEterna Zentaris
Sponsor class: INDUSTRY
First posted: 2021-03-08
Enrollment: 101
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is an open label, single-dose trial to determine the diagnostic efficacy and safety of macimorelin in pediatric subjects aged 2 to less than 18 years of age in whom, based on auxological and clinical criteria, growth hormone stimulation test (GHST) is indicated due to suspected growth hormone deficiency. Four GHSTs will be conducted during the trial: the macimorelin GHST will be performed twice, and arginine and clonidine standard GHSTs will be performed once each. The macimorelin GHST will be administered at the beginning of the trial and after serial performance of the two different standard GHSTs. The macimorelin GHSTs will be performed twice to show repeatability of the macimorelin GHST. All subjects will be randomized 1:1 to the order of the arginine and clonidine GHSTs, and in a crossover manner all subjects will receive both these GHSTs.
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Male and female pediatric subjects from 2 to less than 18 years of age at the time of signing informed consent.
3. Indication for the performance of growth hormone stimulation test.
4. Presence of a height measurement minimum 6 and maximum 18 months prior to screening.

Exclusion Criteria:

1. 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.).
2. Ongoing growth hormone therapy.
3. Presence of hypothyroidism and/or adrenal insufficiency without adequate and stable replacement therapy treatment for at least 30 days prior to first GHST.
4. 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).
5. Medical history of ongoing clinically symptomatic psychiatric disorders.
6. 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.
7. Previous participation in this trial. Participation is defined as signed informed consent.
8. Participation in any clinical trial of an approved or non-approved investigational medicinal product within 30 days before screening.
9. Known or suspected hypersensitivity to trial product(s) or related products;
10. Any disorder, which in the investigator's opinion might jeopardize subject's safety or compliance with the protocol.
11. 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;
12. 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);
13. Current active malignancy other than non-melanoma skin cancer;
14. Female of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice).
15. 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).
16. Lack of ability or willingness to give informed consent by the subject and/or his/her legal representative;
17. Anticipated non-availability for trial visits/procedures.

Primary outcomes:
measure: Area under the Receiver Operator Characteristic curve (ROC AUC) based on GH concentration during GHST following macimorelin administration
timeFrame: 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)).
Secondary outcomes:
measure: Sensitivity for the macimorelin GHST
timeFrame: 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)).
measure: Specificity for the macimorelin GHST
timeFrame: 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)).
measure: Overall agreement between the outcome of the macimorelin GHST and the combined outcome from the 2 standard GHSTs
timeFrame: Visit 4 (between day 11 and day 58)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Angel Wing Clinic For Children With Diabetes
state: Arizona
city: Greenwood Village
country: United States
facility: Pediatric Endocrine Associates, p.c.
state: Colorado
city: Saint Petersburg
country: United States
facility: John Hopkins All Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory Healthcare-Children's Center
state: Georgia
city: Boise
country: United States
facility: St. Luke's Children's Endocrinology
state: Idaho
city: Minneapolis
country: United States
facility: University of Minnesota, Masonic Children's Hospital
state: Minnesota
city: Kansas City
country: United States
facility: The Children's Mercy Hospital - Broadway
state: Missouri
city: Bronx
country: United States
facility: Children's Hospital at Montefiore
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Chapel Hill
country: United States
facility: UNC Hospitals
state: North Carolina
city: Rosharon
country: United States
facility: Alchemi Research Center
state: Texas
city: Tacoma
country: United States
facility: Multicare Health System
state: Washington
city: Yerevan
country: Armenia
facility: Yerevan State Medical University after Mkhitar Heraci
city: Batumi
country: Georgia
facility: JSC Maritime Hospital
city: Tbilisi
country: Georgia
facility: National Institute of Endocrinology
city: Tbilisi
country: Georgia
facility: TSMU Givi Jvania Pediatric Academic Clinik
city: Bielefeld
country: Germany
facility: Evangelisches Klinikum Bethel
city: Ancona
country: Italy
facility: Ospedale Pediatrico G. Salesi
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Anna Meyer
city: Milano
country: Italy
facility: Osp. dei Bambini V. Buzzi, ASST Fatebenefratelli Sacco
city: Parma
country: Italy
facility: Azienda Ospedaliero-Universitaria di Parma Ospedale dei Bambini Pietro Barilla, Clinica Pediatrica
city: Roma
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesù
city: Poznań
country: Poland
facility: MED-POLONIA Sp.z o.o.
city: Rzeszów
country: Poland
facility: Kliniczny Szpital Wojewodzki nr 2 im. Sw. Jadwigi Krolowej w Rzeszowie
city: Szczecin
country: Poland
facility: SPSK Nr 1 im. prof. Tadeusza Sokolowskiego PUM
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
city: Braşov
country: Romania
facility: Cen Med de Diagn si Trat Amb NEOMED
city: Bucharest
country: Romania
facility: Institutul de Endocrinologie "C.I. Parhon"
city: Bucuresti
country: Romania
facility: Sana Monitoring
city: Bucuresti
country: Romania
facility: Medicover Hospitals
city: Constanţa
country: Romania
facility: Spitalul Clinic Judetean de Urgenta "Sf. Apostol Andrei" Constanta
city: Iaşi
country: Romania
facility: Spitalul Clinic Judetean de Urgenta "Sf. Spiridon" Iasi
city: Timişoara
country: Romania
facility: Spitalul Cl. de Urgenta pentru Copii Louis Turcanu Timisoara
city: Târgu-Mureş
country: Romania
facility: Spitalul Clinic Judetean Mures
city: Belgrade
country: Serbia
facility: University children's clinic Belgrade - Department of Endocrinology
city: Niš
country: Serbia
facility: Clinical Center Nis - Clinic for Children's Internal Medicine
city: Novi Sad
country: Serbia
facility: Institute for Child and Youth Health Care of Vojvodina - Endocrinology
city: Bratislava
country: Slovakia
facility: National Institute of Children's Diseases
city: Košice
country: Slovakia
facility: Children's University Hospital Kosice
city: Ľubochňa
country: Slovakia
facility: National Institute of Endocrinology and Diabetology
city: Ljubljana
country: Slovenia
facility: Univerzitetni Klinicni Center Ljubljana - Pediatrics
city: Ankara
country: Turkey
facility: Ankara University, Faculty of Medicine
city: Antalya
country: Turkey
facility: Antalya Training and Research Hospital
city: Kocaeli
country: Turkey
facility: Kocaeli University Faculty of Medicine
city: Ortahisar
country: Turkey
facility: Karadeniz Technical University
Study officials:
affiliation: AEterna Zentaris
name: Nicola K Ammer, MD
role: STUDY_DIRECTOR
References: