| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Multiple sclerosis |
| Sclerosi multipla |
|
| E.1.1.1 | Medical condition in easily understood language |
| Multiple sclerosis |
| sclerosi multipla |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10028053 |
| E.1.2 | Term | MS |
| E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10028245 |
| E.1.2 | Term | Multiple sclerosis |
| E.1.2 | System Organ Class | 10029205 - Nervous system 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 |
| Demonstrate pharmacokinetic bioequivalence of 20 mg ofatumumab injected by prefilled syringe (PFS) or autoinjector (AI) devices |
| Dimostrare la bioequivalenza farmacocinetica della dose di 20 mg di ofatumumab somministrato tramite siringa preriempita o autoiniettore. |
|
| E.2.2 | Secondary objectives of the trial |
Secondary objectives of the Core part:
1. To characterize the pharmacokinetics following subcutaneous administration of ofatumumab to either the abdominal region or the thigh
2. Assessment of immunogenicity
3. Asses the safety and tolorability of ofatumumab
See protocol for complete list of secondary objectives |
Obiettivo 1: Caratterizzare la farmacocinetica di ofatumumab successivamente a somministrazione sottocutanea nella regione addominale o nella coscia
- Obiettivo 2: Valutare l’immunogenicità
- Obiettivo 3: Valutare la sicurezza e la tollerabilità di ofatumumab |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
MS Patients eligible for inclusion in this study must fulfill all of the following criteria:
1. Written informed consent must be obtained before any assessment is performed.
2. Male or Female patients aged 18 to 55 years (inclusive) at screening.
3. Diagnosis of MS according to the 2010 Revised McDonald criteria
4. Relapsing MS: relapsing-remitting course (RRMS), or secondary progressive (SPMS) course with disease activity
5. Disability status at Screening with an EDSS score of 0 to 5.5 (inclusive)
6. Documentation of at least: 1 relapse during the previous 1 year OR 2 relapses during the previous 2 years prior to Screening OR a positive Gd-enhancing MRI scan during the year prior to randomization. Note: Screening MRI scan may be used if no positive Gd enhancing scan exist from prior year.
7. Neurologically stable within 1 month prior to randomization |
¿ Consenso informato scritto, che deve essere ottenuto prima di qualsiasi valutazione prevista
¿ Pazienti di sesso maschile o femminile, di età compresa tra 18 e 55 anni (estremi inclusi) allo screening
¿ Diagnosi di sclerosi multipla (secondo i criteri di Mc Donald rivisti nel 2010)
¿ Sclerosi multipla recidivante: recidivante-remittente o secondaria progressiva con attività di malattia
¿ EDSS allo screening compreso tra 0 e 5,5 (incluso)
¿ Documentazione di almeno: 1 ricaduta nell’ultimo anno o 2 ricadute negli ultimi 2 anni dallo screening, o una risonanza magnetica nucleare positiva al gadolinio nell’anno precedente alla randomizzazione
¿ Neurologicamente stabile nel mese precedente alla randomizzazione |
|
| E.4 | Principal exclusion criteria |
MS Patients fulfilling any of the following criteria are not eligible for inclusion in this study:
1. Patients suspected of not being able or willing to cooperate or comply with study protocol requirements in the opinion of the Investigator
2. Patients with primary progressive MS (Polman et al. 2011) or SPMS without disease activity (Lublin et al. 2014)
3. Patients meeting criteria for neuromyelitis optica (Wingerchuk et al. 2006)
4. Disease duration of more than 10 years in patients with EDSS score of 2 or less
5. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
6. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 12 months after stopping of study medication. Highly effective contraception methods include:
•Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
•Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
•Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject
•Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception
In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking investigational drug.
In case local regulations deviate from the contraception methods listed above, local regulations apply and will be described in the ICF
Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
7. Patients with an active chronic disease (or stable but treated with immune therapy) of the immune system other than MS (e.g. rheumatoid arthritis, scleroderma, Sjögren’s syndrome, Crohn’s disease, ulcerative colitis, etc.) or with immunodeficiency syndrome (hereditary immune deficiency, drug-induced immune deficiency)
8. Patients with active systemic bacterial, viral or fungal infections, or known to have AIDS or to test positive for HIV antibody at Screening
9. Patients with neurological findings consistent with Progressive Multifocal Leukoencephalopathy (PML) or confirmed PML
See protocol for complete list of exclusion criteria |
¿ Pazienti con sclerosi multipla primariamente progressiva o secondariamente progressiva senza attività di malattia
¿ Pazienti che incontrano i criteri per la neuromielite ottica
¿ Durata della malattia superiore a 10 anni in pazienti con EDSS inferiore o uguale a 2
¿ Donne in gravidanza o allattamento
¿ Donne in età fertile, a meno che non utilizzino metodi contraccettivi altamente efficaci
¿ Pazienti con malattia cronica attiva (oppure con malattia stabile, ma trattati con terapia immunitaria) del sistema immunitario diverso dalla sclerosi multipla (es. artrite reumatoide, sclerodermia, sindrome di Sjögren, morbo di Crohn, colite ulcerosa, ecc.) o con sindrome da immunodeficienza (deficienza immunitaria ereditaria, deficienza immunitaria indotta da farmaci)
¿ Pazienti con infezioni sistemiche batteriche, virali o fungine, con AIDS, o positivi al test HIV allo screening
¿ Pazienti con anomalie neurologiche compatibili con la leucoencefalopatia multifocale progressiva (PML) o pazienti con PML confermata
¿ Pazienti a rischio di sviluppo o riattivazione della sifilide o della tubercolosi
¿ Pazienti a rischio di sviluppo o riattivazione dell'epatite |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| AUC and Cmax calculated from data collected in the dosing interval after Week 8 dose administration in accordance with the assessment schedule. |
| AUC e Cmax |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At week 8 and 12. |
| Settimana 8 e 12 |
|
| E.5.2 | Secondary end point(s) |
- AUC
- Cmax
- Proportion of patients with anti-ofatumumab antibodies
- Adverse events including injection related reaction, lab, vital signs, ECG, and eCSSRS |
- AUC
- Cmax
-Proporzione di pazienti con anticorpi anti-ofatumumab
- Eventi avversi , Valutazioni di laboratorio, Segni Vitali, ECG, e eCSSRS |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Up to 12 weeks |
| 12 settimane |
|
| 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 | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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 | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Ofatumumab seringa preriempita |
| Ofatumumab prefilled syringe (PFS) |
|
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 31 |
| 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 |
| Austria |
| Bulgaria |
| Czechia |
| Estonia |
| Germany |
| Italy |
| Latvia |
| Lithuania |
| Poland |
| Russian Federation |
| Spain |
| United States |
|
| 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
|
A patient will complete this study when the patient has completed the End of Study (EOS) visit (Protocol P. 5.6.1 Study completion and post-study treatment
A patient will complete this study when the patient has completed the End of Study (EOS) visit. Patients, who complete the EOS visit (Table 6-1) on study drug, may be eligible for inclusion
in the planned umbrella extension study (under separate protocol).
LPLV |
| Il paziente completerà lo studio quando avrà completato la visita di fine studio. Protocollo P.5.6.1 Fine dello studio e trattamento post-studio. Il paziente completerà lo studio quando avrà completato la visita di fine studio (EOS). I pazienti che completano la visita EOS (Tabella 6-1) sul farmaco in studio possono essere idonei per l'inclusione nello studio di estensione (umbrella extension study) già con protocollo separato. Si specifica che la fine dello studio corrisponde alla LPLV. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 7 |
| 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 | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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