E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Duchenne Muscular Dystrophy |
DISTROFIA MUSCOLARE DI DUCHENNE |
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E.1.1.1 | Medical condition in easily understood language |
Duchenne Muscular Dystrophy (DMD) |
DISTROFIA MUSCOLARE DI DUCHENNE |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10010331 |
E.1.2 | Term | Congenital, familial and genetic disorders |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10013801 |
E.1.2 | Term | Duchenne muscular dystrophy |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic 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 long term safety, tolerability and efficacy of subcutaneous 6mg/kg/week GSK2402968 in subjects with DMD who have participated in either DMD114117 or DMD114044 |
• valutare la sicurezza, l’efficacia e la tollerabilità a lungo termine di GSK2402968, per via sottocutanea, alla dose di 6 mg/kg/settimana in soggetti affetti da DMD che hanno partecipato o allo studio DMD114117 o allo studio DMD114044. |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the long-term PK of subcutaneous 6 mg/kg/week GSK2402968 in subjects with DMD who have participated in either DMD114117 or DMD114044. •To evaluate the long-term impact on health-related quality of life (HRQoL) and functional outcomes of continued treatment with GSK2402968 in subjects with DMD who have participated in either DMD114117 or DMD114044. •To evaluate DMD disease progression and outcomes (clinical, HRQoL and functional) in subjects who discontinue active treatment during the conduct of study (natural history component). •To evaluate the long-term safety, efficacy and PK of an intermittent dosing option in those subjects unable to tolerate GSK2402968 6mg/kg/week dosing. |
•valutare la farmacocinetica (PK) a lungo termine di GSK2402968 per via sottocutanea alla dose di 6 mg/kg/settimana in soggetti affetti da DMD che hanno precedentemente partecipato o allo studio DMD114117 o allo studio DMD114044.•valutare l’impatto a lungo termine sulla qualità della vita correlata alla salute e gli esiti funzionali del trattamento continuativo con GSK2402968 in soggetti affetti da DMD che hanno precedentemente partecipato o allo studio DMD114117 o allo studio DMD114044.•valutare la progressione di malattia della DMD e gli esiti (clinici, HRQoL e funzionali) in soggetti che interrompono il trattamento attivo durante la conduzione dello studio (componente di storia naturale). •valutare nel lungo termine la sicurezza, l’efficacia e la PK di un’opzione di dosaggio intermittente nei soggetti che non riescono a tollerare la dose di 6 mg/kg/settimana di GSK2402968. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects who have successfully completed either the DMD114117 study or DMD114044 study, OR Subjects who withdrew due to safety/tolerability issues, which have since resolved and where in the opinion of the PI along with consultation of the Medical Monitor, it is considered that the benefit of further treatment with GSK2402968 outweighs the risk to the individual subject. OR Subjects who either complete or withdraw early from studies DMD114117 or DMD114044, who do not wish to continue treatment with GSK2402968 but who are willing to participate in the natural history observation arm. 2. Continued use of glucocorticoids with a reasonable expectation that the subject will remain on steroids for the duration of the study. Changes to or cessation of glucocorticosteroids will be at the discretion of the PI in consultation with the subject/parent and the Medical Monitor. 3. Willing and able to comply with all protocol requirements and procedures, 4. Able to give informed assent and/or consent in writing signed by the subject and/or parent(s)/legal guardian (according to local regulations). 5. French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. |
Un soggetto verrà ritenuto eleggibile per questo studio solo se soddisfa tutti i seguenti criteri: 1. -soggetti che hanno completato con successo o lo studio DMD114117 o lo studio DMD114004, OPPURE -soggetti che hanno interrotto lo studio per problemi di sicurezza/tollerabilità, che sono stati risolti e per cui, a giudizio dello sperimentatore e in consultazione con il Medical Monitor, si ritiene che il beneficio di una prosecuzione del trattamento con GSK2402968 superi i rischi per il singolo soggetto, OPPURE -soggetti che completano o che si ritirano prematuramente dagli studi DMD114117 o DMD114044, che non desiderano continuare il trattamento con GSK2402968, ma sono disposti a partecipare al gruppo di osservazione della storia naturale della malattia 2. uso continuativo di glucocorticosteroidi con l’aspettativa ragionevole che il soggetto rimanga in trattamento con steroidi per tutta la durata dello studio. Le variazioni o l’interruzione del trattamento con glucocorticosteroidi saranno a discrezione dello Sperimentatore Principale in consultazione con il soggetto/genitori e con il Medical Monitor 3. soggetti in grado e disposti ad aderire a tutti i requisiti e alle procedure del protocollo 4. soggetti in grado di dare il proprio assenso e/o consenso informato scritto firmato dal soggetto e/o dai genitori/legale rappresentante. |
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E.4 | Principal exclusion criteria |
1. Subject had a serious adverse experience or who met safety stopping criteria that remains unresolved from DMD114117 or DMD114044, which in the opinion of the investigator could have been attributable to study medication, and which is ongoing at Visit 2. Once resolved, subject may be eligible to enrol following PI consultation with the Medical Monitor. 2. Use of anticoagulants, antithrombotics or antiplatelet agents, or previous treatment with investigational drugs except for GSK2402968, within 1 month of the first administration of study medication. 3. Current or anticipated participation in any other investigational clinical studies 4. History of significant medical disorder which may confound the interpretation of either efficacy or safety data e.g. current or history of renal or liver disease/impairment, history of inflammatory illness. |
Un soggetto non sarà considerato idoneo per l’inclusione nello studio se si verifica anche uno solo dei seguenti criteri: 1. soggetti che hanno avuto un evento indesiderato grave o che hanno soddisfatto i criteri di interruzione che restano non risolti dallo studio DMD114117 o DMD114044 che, a giudizio dello sperimentatore, potrebbero essere attribuibili al farmaco in studio e che sono in corso alla Visita 2. Una volta risolti, il soggetto potrà essere eleggibile a seguito di una consultazione dello Sperimentatore Principale con il Medical Monitor 2. uso di agenti anticoagulanti, antitrombotici o antipiastrinici, o precedente trattamento con farmaci sperimentali ad eccezione di GSK2402968 nel mese precedente la prima somministrazione di trattamento in studio. 3. attuale o prevista partecipazione ad altri studi clinici 4. anamnesi di disturbo medico significativo che potrebbe confondere l’interpretazione dei dati di efficacia o di sicurezza, ad esempio anamnesi o presenza di malattia/disfunzione renale o epatica, anamnesi di malattia infiammatoria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Muscle function using 6 minute walking distance (6MWD) test. |
variazione rispetto al basale della distanza percorsa in 6 minuti di cammino (6 Minute Walking Distance - 6MWD) alla settimana 104. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Weeks 12,24,48,72 and Week 104 or Early withdrawal |
SETTIMANE 12,24,48,72 E SETTIMANA 104 OPPURE interruzione anticipata |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints: • Timed function tests (times and grading): • Rise from floor • 4 stair climb • 10m walk/run • Muscle strength (total score): knee flexors, knee extensors, elbow flexors, elbow extensors, shoulder abductors and hip flexors (as determined by handheld myometery) • North Star Ambulatory Assessment • Creatine kinase serum concentrations • Pulmonary function (FEV1, FVC, PCF, PF, sniff pressure test) • Pediatric Quality of Life Neuromuscular module (PedsQL)• Clinician Global Impression of Improvement (CGI-I) • Health Utilities Index (HUI) • Time to major disease milestones (e.g. loss of ambulation, night time ventilation) • Frequency of accidental falls (during 6MWD) • Functional Outcomes assessment Safety endpoints: • Incidence and severity of adverse events. • Vital signs • ECG parameters • Safety haematology and biochemistry parameters including nonstandard parameters such as coagulation parameters (in particular aPTT), serum cystatin C, Complement Factor C3, haptoglobin, fibrinogen, hsCRP, MCP-1 • Urinalysis (including quantitative protein, creatinine and ratio, urine cystatin, KIM-1 and α1-microglobulin) • Echocardiogram Pharmacokinetics: • AUC[0-24], AUC[0-7d], • Cmax • tmax • C24h, • C7d, DEXA Scan Lean body mass and bone density (exploratory endpoint) |
Test di funzionalità cronometrati: o alzarsi dal pavimento o salire 4 scalini o camminare/correre per 10m • forza muscolare: flessori del ginocchio, estensori del ginocchio, flessori del gomito, estensori del gomito, adduttori delle spalle e flessori delle anche (determinazione tramite dinamometro portatile) • valutazione Ambulatory North Star • concentrazioni plasmatiche della creatin-chinasi • funzionalità polmonare (FEV1, FVC, PCF, PF, sniff pressure test) • PedsQL • Clinician Global Impression of Improvement • Health Utilities Index (HUI) • Tempo al raggiungimento delle milestone della malattia • Frequenza di cadute accidentali (durante il 6MWD) • Valutazione degli esiti funzionali .Farmacocinetica . DEXA: massa magra e densità ossea (endpoint esplorativo |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Functional secondary endpoints and collection of questionnaires will be performed at the same intervals as the primary endpoint. Samples for urinalysis and safety labs will be collected Baseline and every two weeks thereafter till visit 104 or Early withdrawal. Predose PK samples will be collected monthly. Serial PK at either Week 12 or 48: prior to treatment and 1/2, 2, 4 hours and between 9-12 hours and 48-72 hours after treatment. Vital signs & ECG Weeks 4,8,16,24,32,40,48,60,72,84,96, and Week 104 or Early withdrawal. Echo & DEXA: Weeks 24, 48, 72, and Week 104 or Early withdrawal. |
End point funzionali: SETTIMANE 12,24,48,72 E SETTIMANA 104 OPPURE interruzione anticipata. Safety ogni 2 settimane. PK ogni mese. |
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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 | 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 | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 |
Argentina |
Australia |
Brazil |
Canada |
Chile |
Israel |
Japan |
Korea, Republic of |
Russian Federation |
Taiwan |
Turkey |
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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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This study has a duration of a minimum of 2 years or until treatment is commercially available locally. |
Lo studio durerà minimo 2 anni o finché il prodotto sarà disponibile in commercio localmente |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 33 |
E.8.9.2 | In all countries concerned by the trial days | 0 |