A Research Study of How Well Macimorelin Works to Find Out if Children Have a Lack of Growth Hormone and How Safe it is

Growth Hormone Deficiency Clinical Trial

— DETECT  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04786873
• Other study ID #: AEZS-130-P02
• Secondary ID: 2018-001989-42U1
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 16, 2021
• Est. completion date: June 2024

Study information

• Verified date: April 2024
• Source: AEterna Zentaris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dwarfism, Pituitary
• Endocrine System Diseases
• Growth Hormone Deficiency

Intervention

Drug:
• Macimorelin
Dosage form: granules for oral solution, Dosage: 1.0 mg/kg body weight, Frequency and duration: single oral dose administration. Macimorelin will be supplied in single-use aluminum pouches (synonymous: sachets) each containing 63.6 mg macimorelin as acetate, which provide 0.5 mg/mL of macimorelin when dissolved in 120 mL of water. The excess amount of 3.6 mg represents an overfill, which is needed to obtain the target concentration.

Diagnostic Test:
• Arginine
For the arginine GHST, R-Gene® 10 from Pfizer will be provided as labelled investigational medicinal product (IMP). After an overnight fast, soluble arginine hydrochloride (0.5 g/kg) will be given i.v. as an infusion with an infusion duration of 30 min.
• Clonidine
For the clonidine GHST, CATAPRESAN® 75 tablets (Boehringer Ingelheim) will be provided as labelled IMP. Each tablet contains 75 ug clonidine hydrochloride. The tablets will be provided in boxes containing 10 tablets. The target dose is 0.15 mg/m2 body surface with a dose range of 0.08 - 0.15 mg/m2. Maximum dose will be 0.25 mg. After an overnight fast, clonidine (0.15 mg/m2 body surface) will be given orally.

Locations

Country	Name	City	State
Armenia	Yerevan State Medical University after Mkhitar Heraci	Yerevan
Georgia	JSC Maritime Hospital	Batumi
Georgia	National Institute of Endocrinology	Tbilisi
Georgia	TSMU Givi Jvania Pediatric Academic Clinik	Tbilisi
Germany	Evangelisches Klinikum Bethel	Bielefeld
Italy	Ospedale Pediatrico G. Salesi	Ancona
Italy	Azienda Ospedaliero-Universitaria Anna Meyer	Firenze
Italy	Osp. dei Bambini V. Buzzi, ASST Fatebenefratelli Sacco	Milano
Italy	Azienda Ospedaliero-Universitaria di Parma Ospedale dei Bambini Pietro Barilla, Clinica Pediatrica	Parma
Italy	IRCCS Ospedale Pediatrico Bambino Gesù	Roma
Poland	MED-POLONIA Sp.z o.o.	Poznan
Poland	Kliniczny Szpital Wojewodzki nr 2 im. Sw. Jadwigi Krolowej w Rzeszowie	Rzeszów
Poland	SPSK Nr 1 im. prof. Tadeusza Sokolowskiego PUM	Szczecin
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu	Wroclaw
Romania	Cen Med de Diagn si Trat Amb NEOMED	Brasov
Romania	Institutul de Endocrinologie "C.I. Parhon"	Bucharest
Romania	Medicover Hospitals	Bucuresti
Romania	Sana Monitoring	Bucuresti
Romania	Spitalul Clinic Judetean de Urgenta "Sf. Apostol Andrei" Constanta	Constanta
Romania	Spitalul Clinic Judetean de Urgenta "Sf. Spiridon" Iasi	Iasi
Romania	Spitalul Clinic Judetean Mures	Târgu-Mures
Romania	Spitalul Cl. de Urgenta pentru Copii Louis Turcanu Timisoara	Timisoara
Serbia	University children's clinic Belgrade - Department of Endocrinology	Belgrade
Serbia	Clinical Center Nis - Clinic for Children's Internal Medicine	Niš
Serbia	Institute for Child and Youth Health Care of Vojvodina - Endocrinology	Novi Sad
Slovakia	National Institute of Children's Diseases	Bratislava
Slovakia	Children's University Hospital Kosice	Košice
Slovakia	National Institute of Endocrinology and Diabetology	Lubochna
Slovenia	Univerzitetni Klinicni Center Ljubljana - Pediatrics	Ljubljana
Turkey	Ankara University, Faculty of Medicine	Ankara
Turkey	Antalya Training and Research Hospital	Antalya
Turkey	Kocaeli University Faculty of Medicine	Kocaeli
Turkey	Karadeniz Technical University	Ortahisar
United States	Emory Healthcare-Children's Center	Atlanta	Georgia
United States	St. Luke's Children's Endocrinology	Boise	Idaho
United States	Children's Hospital at Montefiore	Bronx	New York
United States	UNC Hospitals	Chapel Hill	North Carolina
United States	Pediatric Endocrine Associates, p.c.	Greenwood Village	Colorado
United States	The Children's Mercy Hospital - Broadway	Kansas City	Missouri
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	Alchemi Research Center	Rosharon	Texas
United States	John Hopkins All Children's Hospital	Saint Petersburg	Florida
United States	Multicare Health System	Tacoma	Washington
United States	Angel Wing Clinic For Children With Diabetes	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
AEterna Zentaris

Countries where clinical trial is conducted

United States,  Armenia,  Georgia,  Germany,  Italy,  Poland,  Romania,  Serbia,  Slovakia,  Slovenia,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the Receiver Operator Characteristic curve (ROC AUC) based on GH concentration during GHST following macimorelin administration	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).	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	Sensitivity for the macimorelin GHST	Sensitivity (confirmatory secondary endpoint) will be derived from the empirical ROC plot using this GH cut-off point.	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	Specificity for the macimorelin GHST	Specificity (confirmatory secondary endpoint) will be derived from the empirical ROC plot using this GH cut-off point.	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	Overall agreement between the outcome of the macimorelin GHST and the combined outcome from the 2 standard GHSTs	Agreement between the outcome of macimorelin and the combined outcome of the 2 standard GHSTs will be evaluated by 'percent overall agreement'.	Visit 4 (between day 11 and day 58)