E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult Growth Hormone Deficiency (AGHD) |
Deficiencia de Hormona del Crecimiento en Adultos (DHCA) |
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E.1.1.1 | Medical condition in easily understood language |
Lack of growth hormone in the body |
Falta de la hormona del crecimeinto en el cuerpo |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10056438 |
E.1.2 | Term | Growth hormone deficiency |
E.1.2 | System Organ Class | 10014698 - Endocrine disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety of once-weekly lonapegsomatropin in adults with GHD previously treated in trial TCH-306. |
Evaluar la seguridad de la lonapegsomatropina administrada una vez por semana en adultos con GHD tratados previamente en el ensayo TCH-306. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the efficacy of once-weekly lonapegsomatropin in adults with GHD. 2. To evaluate the pharmacodynamics (PD) of once-weekly lonapegsomatropin in adults with GHD. 3. To evaluate the pharmacokinetics (PK) of once-weekly lonapegsomatropin in adults with GHD. |
1. Evaluar la eficacia de la lonapegsomatropina administrada una vez por semana en adultos con GHD. 2. Evaluar la farmacodinámica (FD) de lonapegsomatropina administrada una vez por semana en adultos con GHD. 3. Evaluar la farmacocinética (FC) de lonapegsomatropina una vez por semana en adultos con GHD.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signing of the trial specific informed consent. 2. Completion of the treatment period and Visit 7 assessments of trial TCH-306, including collection and upload of Visit 7 DXA scan. 3. Fundoscopy at Visit 7 in trial TCH-306 without signs/symptoms of intracranial hypertension or diabetic retinopathy stage 2 / moderate or above. |
1. Firma del consentimiento informado específico del ensayo. 2. Finalización del período de tratamiento y evaluaciones de la visita 7 del ensayo TCH-306, incluyendo la recopilación y subida del escaneo DXA de la Visita 7. 3. Fundoscopia en la Visita 7 en el ensayo TCH-306 sin signos/síntomas de hipertensión intracraneal o retinopatía diabética estadio 2 / moderado o superior.
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E.4 | Principal exclusion criteria |
1. Diabetes mellitus if any of the following are met: a. Poorly controlled diabetes, defined as HbA1C higher than 7.5% according to central laboratory at Visit 6 in trial TCH-306 b. Use of diabetes mellitus drugs other than metformin and/or dipeptidyl peptidase-4 (DPP- 4) inhibitors 2. Active malignant disease or history of malignancy. Exceptions are: a. Resection of in situ carcinoma of the cervix uteri b. Complete eradication of squamous cell or basal cell carcinoma of the skin 3. Known history of hypersensitivity and/or idiosyncrasy to the investigational product (somatropin or excipients) 4. Female who is pregnant, plans to become pregnant, or is breastfeeding 5. Female participant of childbearing potential (i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile) not willing throughout the trial to use contraceptives as required by local law or practice. Details included in Appendix 4/section 10.4 of this protocol 6. Male participant not willing throughout the trial to use contraceptives as required by local law or practice. Details included in Appendix 4/ section 10.4 of this protocol 7. Any disease or condition that, in the judgement of the investigator, may make the participant unlikely to comply with the requirements of the protocol or any condition that presents undue risk from the investigational product or trial procedures 8. eGFR <60 mL/min/1.73m² determined based on Modification of Diet in Renal Disease (MDRD) equation using serum creatinine from the central laboratory at screening 9. Hepatic transaminases (ie, AST or ALT) >3 times the upper limit of normal according to the central laboratory at screening
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1. Diabetes mellitus si se cumple alguno de los siguientes: a. Diabetes mal controlada, definida como HbA1C superior al 7,5% según el laboratorio central en la visita 6 en el ensayo TCH-306. b. Uso de cualquier medicamento para la diabetes mellitus distinto de metformina y/o inhibidores de dipeptidil peptidasa-4 (DPP-4). 2. Enfermedad maligna activa o antecedentes de neoplasia maligna. Las excepciones son: a. Resección de carcinoma cervicouterino in situ b. Erradicación completa del carcinoma de células escamosas o de células basales de la piel 3. Antecedentes conocidos de hipersensibilidad y/o idiosincrasia al producto en investigación (somatropina o excipientes) 4. Mujer que está embarazada, planea quedar embarazada o se encuentra en período de lactancia. 5. Participante femenina en edad fértil (es decir, fértil, después la menarquia y hasta volverse posmenopáusica, a menos que esté permanentemente estéril) que no esté dispuesta a usar métodos anticonceptivos durante todo el ensayo según lo requieran las leyes o prácticas locales. Detalles incluidos en el Apéndice 4/sección 10.4 de este protocolo 6. El participante masculino no esté dispuesto a usar métodos anticonceptivos durante todo el ensayo según lo requiera la legislación o prácticas locales. Detalles incluidos en el Apéndice 4/sección 10.4 de este protocolo 7. Cualquier enfermedad o afección que, a juicio del investigador, pueda hacer que sea poco probable que el sujeto cumpla con los requisitos del protocolo o cualquier afección que presente un riesgo del producto en investigación o de los procedimientos del ensayo. 8. TFGe <60 ml/min/1,73 m² determinada según la ecuación de modificación de la dieta en la enfermedad renal (MDRD) utilizando la creatinina sérica del laboratorio central en la selección. 9. Transaminasas hepáticas (es decir, AST o ALT) > 3 veces el límite superior de la normalidad según el laboratorio central en la selección
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E.5 End points |
E.5.1 | Primary end point(s) |
• Adverse events (AEs) • Laboratory values • Vital signs • Immunogenicity • 12-lead electrocardiogram (ECGs) • Fundoscopy |
• Eventos adversos (EA) • Valores analíticos • Constantes vitales • Inmunogenicidad • Electrocardiograma (ECG) de 12 derivaciones • Fundoscopia
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
throughout the treatment period of 52 weeks |
durante todo el período de tratamiento de 52 semanas |
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E.5.2 | Secondary end point(s) |
Efficacy endpoints (as assessed by dual-X-rayabsorptiometry (DXA): • Trunk percent fat • Trunk fat mass • Total body lean mass
PD endpoints: • IGF-1 values and IGF-1 SDS
PK endpoints: • hGH, lonapegsomatropin, and mPEG values |
Criterios de valoración de la eficacia (evaluados mediante absorciometría de rayos X de energía dual (DXA)): • Porcentaje de grasa del tronco • Masa grasa del tronco • Masa magra corporal total
Citerios de valoración FD: • Niveless de IGF-1 y SDS de IGF-1
Criterios de valoración FC: • Niveles de hGH, lonapegsomatropina y mPEG
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy endpoints At week 52 PD endpoints throughout the treatment period of 52 weeks PK endpoints from week 17 to week 52 |
Criterios de valoración de la eficacia en la semana 52 Criterios de valoración de la FD a lo largo del período de tratamiento de 52 semanas Criterios de valoración de FC desde la semana 17 hasta la semana 52
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 48 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Israel |
Japan |
New Zealand |
United States |
France |
Poland |
Bulgaria |
Netherlands |
Romania |
Spain |
Germany |
Greece |
Italy |
Armenia |
Belarus |
Denmark |
Georgia |
Russian Federation |
Slovakia |
Turkey |
Ukraine |
United Kingdom |
Serbia |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 6 |