Studio volto a valutare la sicurezza, l’efficacia, la farmacocinetica e la farmacodinamica di RO7112689 in volontari sani e in pazienti con Emoglobinuria Parossistica Notturna

Phase 1

• Conditions: Paroxysmal nocturnal hemoglobinuria (PNH); MedDRA version: 20.1Level: LLTClassification code 10055629Term: Paroxysmal nocturnal hemoglobinuriaSystem Organ Class: 100000004857; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2016-002128-10-IT
• Lead Sponsor: F. HOFFMANN - LA ROCHE LTD.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-02-06
• Last Update Posted: 19 March 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 49

Inclusion Criteria

Part 1 (HVs only)
• Healthy male volunteers between the age of 21 and 55 years
• Neisseria meningitidis vaccination against serogroups B and A, C, W, and Y
• Subjects with a negative hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C antibody, and HIV test result are eligible for the study
• Subjects who have been vaccinated against hepatitis B

Parts 2 and 3 (PNH patients only)
• Male or female patients between the age of 18 and 75 years
• Hepatitis B patients can be enrolled if their LFT values are less than 2 xULN and there is no liver function impairment
• Neisseria meningitidis vaccination in accordance with most current local guidelines or Standard of Care (SOC) for patients at increased risk for meningococcal disease (Part 2)
• Patient has been vaccinated with Neisseria meningitidis vaccine(s) in accordance with most current local guidelines or SOC for patients at increased risk for meningococcal disease or is being revaccinated if applicable (Part 3)
• Stable dose for >= 28 days prior to screening of other therapies (immunosuppressant therapy, corticosteroids, iron supplements)
• Negative pregnancy test for women of childbearing potential

Part 2 only (currently untreated PNH patients who are candidates for treatment with complement inhibitors only):
• PNH patients who have not been treated with any complement inhibitor or if previously treated stopped treatment due to lack of efficacy based on a single missense C5 heterozygous mutation

Part 3 only (PNH patients currently treated with eculizumab only):
• Patients are adequately controlled based on investigator opinion
• Patients receive regular infusions of eculizumab

OLE only - PNH patients:
• PNH patients who have completed Parts 2 and 3 respectively
• PNH patients who derived, in the Investigator's opinion, benefit from treatment with RO7112689
Are the trial subjects under 18? no
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 9

Exclusion Criteria

Parts 1, 2, and 3:
• Known or suspected hereditary complement deficiency
• History of meningococcal meningitis
• Any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 28 days prior to screening or oral antibiotics within 2 weeks prior to screening and up to first study drug administration
• History of or currently active primary or secondary immunodeficiency, including known history of HIV infection
• Evidence of malignant disease including myelodysplastic syndrome, or malignancies diagnosed within the previous 5 years

Part 1 (HVs only):
• Any clinically relevant history or the presence of moderate to severe respiratory, renal, hepatic, gastrointestinal, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, or connective tissue disease
• Any major illness within one month before the screening examination or any febrile illness within 2 weeks prior to screening and up to first study drug administration
• History or presence of clinically significant electrocardiogram (ECG) abnormalities or cardiovascular disease
• Congenital or acquired complement deficiency
• Carriers of Neisseria meningitides based on cultures from naso-pharyngeal swabs

Parts 2 and 3 (PNH patients only):
• Evidence of moderate to severe concurrent renal, liver, cardiac, pulmonary or gastrointestinal disease not related to PNH as determined by the Investigator
• History of bone marrow transplantation
• Treatment with azathioprine or erythrocyte-stimulating agents within 14 days prior to first study drug administration

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified