| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Atherosclerotic cardiovascular disease and Obesity |
| Malattia cardiovascolare aterosclerotica e obesità |
|
| E.1.1.1 | Medical condition in easily understood language |
| Cardiovascular disease and Body weight above the healthy range |
| Malattie cardiovascolari e peso corporeo al di sopra del range sano |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10051615 |
| E.1.2 | Term | Atherosclerotic cardiovascular disease |
| E.1.2 | System Organ Class | 100000004866 |
|
| 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 | 10029883 |
| E.1.2 | Term | Obesity |
| E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To confirm non-inferiority of CagriSema 2.4 mg/2.4 mg versus placebo with respect to time to first major adverse cardiovascular event (MACE) when at least 122 MACE have been accrued |
| Per confermare la non inferiorità di CagriSema 2,4 mg/2,4 mg rispetto al placebo rispetto al tempo al primo evento avverso cardiovascolare maggiore (MACE) quando sono state accumulate almeno 122 MACE |
|
| E.2.2 | Secondary objectives of the trial |
- To confirm superiority of CagriSema 2.4 mg/2.4 mg versus placebo
with respect to time to first MACE at final database lock.
- To compare the effect of CagriSema 2.4 mg/2.4 mg versus placebo on:
a. CV outcomes (as defined by the secondary supportive endpoints)
b. CV risk factors
c. Body weight
d. Glucose metabolism
e. SF-36v2 physical and mental components of health
- To compare the safety and tolerability of CagriSema 2.4 mg/2.4 mg
versus placebo |
- Per confermare la superiorità di CagriSema 2,4 mg/2,4 mg rispetto al placebo per quanto riguarda il tempo al primo MACE al blocco finale del database.
- Per confrontare l'effetto di CagriSema 2,4 mg/2,4 mg rispetto al placebo su: un. Esiti CV (come definiti dagli endpoint secondari di supporto)
b. Fattori di rischio CV
c. Peso corporeo
d. Metabolismo del glucosio
e. SF-36v2 componenti fisiche e mentali della salute
- Per confrontare la sicurezza e la tollerabilità di CagriSema 2,4 mg/2,4 mg rispetto al placebo |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Male or female
- Age above or equal to 55 years at the time of signing informed consent.
- Body mass index (BMI) above or equal 30.0 kg/m^2
- Established CVD as evidenced by at least one of the following:
- Prior myocardial infarction
- Prior stroke (ischemic or haemorrhagic stroke)
- Symptomatic peripheral arterial disease (PAD) defined as at least one of the following:
a. Intermittent claudication with an Ankle-brachial index (ABI) below 0.85 at rest
b. Intermittent claudication with a above or equal 50% stenosis in a
lower extremity peripheral artery documented by X-ray angiography, MR angiography, CT angiography or Doppler ultrasound
c. Prior revascularization procedure of a lower extremity peripheral artery
d. Lower extremity amputation at or above ankle due to atherosclerotic
disease (excluding e.g., trauma or osteomyelitis)
For participants with T2D at screening the following inclusion criteria also apply:
- Diagnosed with type 2 diabetes mellitus (T2D) above or equal to 180 days before screening
- HbA1c 7%-10% (53-86 mmol/mol) (both inclusive), as measured by central laboratory at screening.
- Treatment with either:
a. Lifestyle intervention alone
b. 1-3 marketed oral antidiabetic drugs (OAD)s (metformin, a-
glucosidase inhibitors (AGI), glinides, sodium-glucose co-transporter 2
inhibitor (SGLT2i), DPP4-inhibitors, thiazolidinediones, or sulphonylureas (SU) as a single agent or in combination) according to local label
c. Basal insulin alone or in combination with up to two marketed OADs (refer to b. above), all according to local label |
- Maschio o femmina
- Età superiore o uguale a 55 anni al momento della sottoscrizione del consenso informato.
- Indice di massa corporea (BMI) superiore o uguale a 30,0 kg/m^2
- CVD accertato come evidenziato da almeno uno dei seguenti:
- Pregresso infarto del miocardio
- Ictus precedente (ictus ischemico o emorragico)
- Arteriopatia periferica sintomatica (PAD) definita come almeno uno dei seguenti:
un. Claudicatio intermittente con indice caviglia-braccio (ABI) inferiore a 0,85 a riposo
b. Claudicatio intermittente con stenosi superiore o uguale al 50% in a
arteria periferica degli arti inferiori documentata mediante angiografia a raggi X, angio-RM, angio-TC o ecografia Doppler
c. Precedente procedura di rivascolarizzazione di un'arteria periferica dell'arto inferiore
d. Amputazione degli arti inferiori in corrispondenza o sopra la caviglia per aterosclerotica
malattia (esclusi ad es. trauma o osteomielite)
Per i partecipanti con T2D allo screening si applicano anche i seguenti criteri di inclusione:
- Diagnosi di diabete mellito di tipo 2 (T2D) superiore o uguale a 180 giorni prima dello screening
- HbA1c 7%-10% (53-86 mmol/mol) (entrambi inclusi), misurata dal laboratorio centrale allo screening.
- Trattamento con:
un. Solo intervento sullo stile di vita
b. 1-3 farmaci antidiabetici orali (OAD) commercializzati (metformina, a-
inibitori della glucosidasi (AGI), glinidi, co-trasportatore sodio-glucosio 2
inibitore (SGLT2i), inibitori della DPP4, tiazolidinedioni o sulfaniluree (SU) come agente singolo o in combinazione) secondo l'etichetta locale
c. Insulina basale da sola o in combinazione con un massimo di due OAD commercializzati (fare riferimento a b. sopra), il tutto in base all'etichetta locale |
|
| E.4 | Principal exclusion criteria |
- Myocardial infarction, stroke, hospitalization for unstable angina
pectoris or transient ischaemic attack within 60 days before screening
- Planned coronary, carotid or peripheral artery revascularisation known
on the day of screening
- Heart failure classified as being in New York Heart Association (NYHA)
Class IV at screening
- Treatment with any GLP-1 RA or a medication with GLP-1 activity
within 90 days before screening
- End stage renal disease defined as eGFR below 15 mL/min/1.73 m^2,
as measured by the central laboratory at screening
- Chronic or intermittent haemodialysis or peritoneal dialysis |
- Infarto miocardico, ictus, ricovero per angina instabile
pectoris o attacco ischemico transitorio entro 60 giorni prima dello screening
- Nota rivascolarizzazione pianificata dell'arteria coronarica, carotidea o periferica
il giorno della proiezione
- Insufficienza cardiaca classificata nella New York Heart Association (NYHA)
Classe IV allo screening
- Trattamento con qualsiasi GLP-1 RA o un farmaco con attività GLP-1
entro 90 giorni prima dello screening
- Malattia renale allo stadio terminale definita come eGFR inferiore a 15 ml/min/1,73 m^2,
come misurato dal laboratorio centrale allo screening
- Emodialisi cronica o intermittente o dialisi peritoneale |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Time to first occurrence of MACE, a composite endpoint consisting of:
CV death, non-fatal myocardial infarction, non-fatal stroke |
| 1. Tempo alla prima occorrenza di MACE, un endpoint composito costituito da: Morte CV, infarto miocardico non fatale, ictus non fatale |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 1. From baseline (week 0) to end of study (up to 163 weeks or more) |
| 1. Dal basale (settimana 0) alla fine dello studio (fino a 163 settimane o più) |
|
| E.5.2 | Secondary end point(s) |
1. Time to first occurrence of MACE, a composite endpoint consisting of:
CV death, non-fatal myocardial infarction, non-fatal stroke.
2. Time to first occurrence of an expanded MACE composite endpoint
consisting of: CV death, non-fatal myocardial infarction,non-fatal stroke,
coronary revascularisation, unstable angina requiring hospitalisation.
3. Time to first occurrence of a composite heart failure endpoint
consisting of: CV death, heart failure hospitalisation, urgent heart failure
visit.
4. Time to first occurrence of a composite endpoint consisting of: allcause
death, non-fatal myocardial infarction, non-fatal stroke.
5. Time to occurrence of CV death
6. Time to first occurrence of non-fatal myocardial infarction
7. Time to first occurrence of non-fatal stroke
8. Relative change in body weight
9. Change in waist circumference
10. Change in systolic blood pressure (SBP)
11. Change in diastolic blood pressure (DBP)
12. Relative change in lipids: Total cholesterol, HDL cholesterol, LDL
cholesterol, VLDL cholesterol, Triglycerides, Free fatty acids
13. Change in HbA1c
14. Change in SF-36v2: Physical Component Summary score, Mental
Component Summary score
15. Number of TESAEs
16. Number of event adjudication committee (EAC)-confirmed malignant
neoplasms
17. Number of severe hypoglycaemic episodes (level 3) (only for
participants with T2D at screening) |
1. Tempo alla prima occorrenza di MACE, un endpoint composito costituito da:
Morte CV, infarto miocardico non fatale, ictus non fatale.
2. Tempo alla prima occorrenza di un endpoint composito MACE espanso
consistente in: morte CV, infarto miocardico non fatale, ictus non fatale,
rivascolarizzazione coronarica, angina instabile che richiede il ricovero in ospedale.
3. Tempo alla prima occorrenza di un endpoint composito di insufficienza cardiaca
composto da: morte CV, ricovero per scompenso cardiaco, scompenso cardiaco urgente
visitare.
4. Tempo alla prima occorrenza di un endpoint composto composto da: allcause
morte, infarto miocardico non fatale, ictus non fatale.
5. Tempo al verificarsi della morte CV
6. Tempo alla prima insorgenza di infarto miocardico non fatale
7. Tempo alla prima occorrenza di ictus non fatale
8. Modifica relativa del peso corporeo
9. Modifica della circonferenza della vita
10. Variazione della pressione arteriosa sistolica (SBP)
11. Variazione della pressione diastolica (DBP)
12. Modifica relativa dei lipidi: colesterolo totale, colesterolo HDL, LDL
colesterolo, colesterolo VLDL, trigliceridi, acidi grassi liberi
13. Modifica dell'HbA1c
14. Modifica in SF-36v2: punteggio Riepilogo componenti fisiche, Mentale
Punteggio di riepilogo dei componenti
15. Numero di TESAE
16. Numero di maligni confermati dal comitato di aggiudicazione dell'evento (EAC).
neoplasie
17. Numero di episodi ipoglicemici gravi (livello 3) (solo per
partecipanti con T2D allo screening) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.- 7. From baseline (week 0) to end of study (up to 163 weeks or more)
8.- 14. From baseline (week 0) to end of treatment (week 156).
15.- 17. From baseline (week 0) to end of study (up to 163 weeks or more) |
1.- 7. Dal basale (settimana 0) alla fine dello studio (fino a 163 settimane o Di più)
8.- 14. Dal basale (settimana 0) alla fine del trattamento (settimana 156).
15.- 17. Dal basale (settimana 0) alla fine dello studio (fino a 163 settimane o Di più) |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| Tolerability |
| Tollerabilità |
|
| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| 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 | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 13 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 63 |
| 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 | Information not present in EudraCT |
| 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 |
| Argentina |
| Australia |
| Brazil |
| Canada |
| Colombia |
| India |
| Japan |
| Mexico |
| South Africa |
| United States |
| Russian Federation |
| Turkey |
| United Kingdom |
| Serbia |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 5 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| 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 | 5 |
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