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

NCT ID: NCT04786873

Last Updated: 2024-08-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-16
• Study Completion Date: 2024-06-13

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.

Conditions

Growth Hormone Deficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: SINGLE

Study Groups

standard GHST order randomized: arginine - 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.

Group Type: ACTIVE_COMPARATOR

Macimorelin

Intervention Type: DRUG

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.

Arginine

Intervention Type: DIAGNOSTIC_TEST

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

Intervention Type: DIAGNOSTIC_TEST

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.

standard GHST order randomized: clonidine - 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.

Group Type: ACTIVE_COMPARATOR

Macimorelin

Intervention Type: DRUG

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.

Arginine

Intervention Type: DIAGNOSTIC_TEST

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

Intervention Type: DIAGNOSTIC_TEST

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DIAGNOSTIC_TEST

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.

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

Macrilen; AEZS-130; Macimorelin GHST; Macimorelin test; Macrilen GHST; Macrilen test; R-Gene 10; arginine test; arginine GHST; Catapressan 75; Clonidine test; Clonidine GHST

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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AEterna Zentaris

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicola K Ammer, MD

Role: STUDY_DIRECTOR

AEterna Zentaris

Locations

Angel Wing Clinic For Children With Diabetes

Tucson, Arizona, United States

Pediatric Endocrine Associates, p.c.

Greenwood Village, Colorado, United States

John Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Emory Healthcare-Children's Center

Atlanta, Georgia, United States

St. Luke's Children's Endocrinology

Boise, Idaho, United States

University of Minnesota, Masonic Children's Hospital

Minneapolis, Minnesota, United States

The Children's Mercy Hospital - Broadway

Kansas City, Missouri, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Children's Hospital at Montefiore

The Bronx, New York, United States

UNC Hospitals

Chapel Hill, North Carolina, United States

Alchemi Research Center

Rosharon, Texas, United States

Multicare Health System

Tacoma, Washington, United States

Yerevan State Medical University after Mkhitar Heraci

Yerevan, , Armenia

JSC Maritime Hospital

Batumi, , Georgia

National Institute of Endocrinology

Tbilisi, , Georgia

TSMU Givi Jvania Pediatric Academic Clinik

Tbilisi, , Georgia

Evangelisches Klinikum Bethel

Bielefeld, , Germany

Ospedale Pediatrico G. Salesi

Ancona, , Italy

Azienda Ospedaliero-Universitaria Anna Meyer

Florence, , Italy

Osp. dei Bambini V. Buzzi, ASST Fatebenefratelli Sacco

Milan, , Italy

Azienda Ospedaliero-Universitaria di Parma Ospedale dei Bambini Pietro Barilla, Clinica Pediatrica

Parma, , Italy

IRCCS Ospedale Pediatrico Bambino Gesù

Roma, , Italy

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, , Poland

Cen Med de Diagn si Trat Amb NEOMED

Brasov, , Romania

Sana Monitoring

Bucharest, , Romania

Medicover Hospitals

Bucharest, , Romania

Institutul de Endocrinologie "C.I. Parhon"

Bucharest, , Romania

Spitalul Clinic Judetean de Urgenta "Sf. Apostol Andrei" Constanta

Constanța, , Romania

Spitalul Clinic Judetean de Urgenta "Sf. Spiridon" Iasi

Iași, , Romania

Spitalul Clinic Judetean Mures

Târgu Mureş, , Romania

Spitalul Cl. de Urgenta pentru Copii Louis Turcanu Timisoara

Timișoara, , Romania

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, , Serbia

National Institute of Children's Diseases

Bratislava, , Slovakia

Children's University Hospital Kosice

Košice, , Slovakia

National Institute of Endocrinology and Diabetology

Ľubochňa, , Slovakia

Univerzitetni Klinicni Center Ljubljana - Pediatrics

Ljubljana, , Slovenia

Ankara University, Faculty of Medicine

Ankara, , Turkey (Türkiye)

Antalya Training and Research Hospital

Antalya, , Turkey (Türkiye)

Kocaeli University Faculty of Medicine

Kocaeli, , Turkey (Türkiye)

Karadeniz Technical University

Ortahisar, , Turkey (Türkiye)

Countries

United States; Armenia; Georgia; Germany; Italy; Poland; Romania; Serbia; Slovakia; Slovenia; Turkey (Türkiye)

Other Identifiers

2018-001989-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1248-5075

Identifier Type: OTHER

Identifier Source: secondary_id

AEZS-130-P02

Identifier Type: -

Identifier Source: org_study_id