Paroxysmal nocturnal hemoglobinuria (PNH) MedDRA version: 19.0 Level: LLT Classification code 10055629 Term: Paroxysmal nocturnal hemoglobinuria System Organ Class: 100000004857
Conditions
Interventions
Product Code: RO7112689/F01
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Not available
CAS Number: 1917321-26-6
Current Sponsor code: RO7112689
Other descriptive name: C5
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Parts 1, 2, and 3: - Subjects who have been vaccinated against hepatitis B Part 1 (HVs only) - Healthy male volunteers between the age of 21 and 55 years - Willing to comply with a non-smoking policy during the in-clinic portion of the study Parts 2 and 3 (PNH patients only) - Male or female patients between the age of 18 and 75 years - 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 - Patients had >=2 RBC transfusions in the past 12 months Part 3 only (PNH patients currently treated with eculizumab only): - Patients are adequately controlled (=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
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, 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Safety and PD (Parts 1, 2, and 3): 1-5. Approximately 6 months for Part 1; approximately 8 months for Parts 2 and 3;Primary end point(s): Safety (Parts 1, 2, and 3): 1. Incidence of dose-limiting events 2. Incidence and severity of adverse events (AEs), serious adverse events and AEs leading to withdrawal PD (Parts 1, 2, and 3): 3. Ex vivo liposome lysis in serum and ex-vivo lysis of antibody-coated erythrocytes 4. Total and target engaged C5 concentration 5. Serum LDH;Main Objective: Part 1 •Evaluate the safety and tolerability of single doses of RO7112689 in healthy volunteers (HVs) Part 2 and 3 •Evaluate the safety and tolerability of RO7112689 for a total duration of 5 months in treatment naïve patients with PNH and PNH patients switching treatment to RO7112689 •Evaluate the pharmacodynamic (PD) effect of multiple doses of RO7112689 on complement activity in patients with PNH ;Secondary Objective: Part 1 •Characterize the PD effects of a single-dose of RO7112689 on complement activity (CA) & other related biomarkers •Describe the single-dose pharmacokinetic (PK) profile of RO7112689 •Assess the bioavailability of subcutaneous (SC) administration of RO7112689 •Assess ethnic sensitivities across Japanese & non-Japanese HVs Part 2 & 3 •Describe the multiple-dose PK properties of RO7112689 in treatment naïve patients (Pts) with PNH and PNH Pts switching treatment to RO7112689 •Characterize other PD effects of RO7112689 •Characterize the exposure-response relationship of RO7112689 following different SC dosing regimens •Assess the efficacy, Pt-related outcomes & treatment satisfaction of RO7112689 in treatment naïve Pts with PNH, and/or PNH Pts switching treatment to RO7112689 Parts 1, 2 & 3 •Explore the PK/PD relationship of single-ascending & multiple doses of RO7112689 on CA & other related biomarkers •Evaluate the immunogenicity of RO7112689 in HVs and in Pts with PNH | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy (Parts 2 and 3): 1. Change in LDH 2. Change in free-haemoglobin 3. Proportion of patients with stabilized haemoglobin levels 4. Change in fatigue as measured by the functional assessment of chronic illness therapy fatigue 5. Change in health-related quality of life as measured by the European Organization for Research and Treatment of Cancer quality of life questionnaire-core 30 6. Number of packed RBC units transfused per patient PK (Parts 1, 2, and 3): 7. Pharmacokinetic profile of RO7112689; Cmax, Tmax, AUC, T1/2, bioavailability following SC administration;Timepoint(s) of evaluation of this end point: Efficacy and PK (Parts 1, 2, and 3): 1-7. Approximately 6 months for Part 1; approximately 8 months for Parts 2 and 3 | — |
Countries
Brazil, Czech Republic, France, Germany, Hungary, Italy, Japan, Netherlands, United Kingdom
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd
Outcome results
None listed