A Study to Assess Safety, Effectiveness, Pharmacokinetics, and Pharmacodynamics of RO7112689 in Healthy Volunteers and Patients With Paroxysmal Nocturnal Hemoglobinuria
- Conditions
- Paroxysmal nocturnal hemoglobinuria (PNH)MedDRA version: 21.1Level: LLTClassification code 10055629Term: Paroxysmal nocturnal hemoglobinuriaSystem Organ Class: 100000004857Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2016-002128-10-DE
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 49
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
- Willing to comply with a non-smoking policy during the in-clinic portion
of the study
Parts 2, 3 and 4 (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 and Part 4 Arm A)
- 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 and Part 4 Arm B)
- 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 and Part 4 Arm A only (currently untreated PNH patients who are
candidates for treatment with complement inhibitors only):
- Hepatitis B patients can be enrolled if their LFT values are less than 2 × ULN and there is no liver function impairment
- 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 and Part 4 Arm B only (PNH patients currently treated with eculizumab only):
- 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.
o Subjects seropositive for HCV but adequately treated without detectable HCV RNA are eligible
o Subjects who have been vaccinated against hepatitis B are eligible
o Subjects seropositive for HBV but adequately treated without detectable HBV DNA are eligible
- 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, 3 and 4 respectively
- PNH patients who derived, in the Investigator's opinion, benefit from treatment with crovalimab
- For women who are not post menopausal and have not undergone surgical sterilization agreement to remain abstinent or use a contraception method that results in a failure rate of <1% per year, during the treatment period and for 5.5 half-lives or at least t 10.5 months after the last dose of crovalimab
- Vaccination currency for Neisseria meningitidis serotypes A, C, W, Y and B should be maintained throughout the OLE, according to local guidelines or SOC as applicable in patients with complement deficiency.
In the absence of clear local guidelines for Neisseria meningitidis, the Advisory Committee on Immunization Practices (ACIP) 2020 Guidelines are recommended
Are the trial subjects under 18? no
Number of subjects for this age range:
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
Parts 1, 2, 3 and 4:
- 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
- Pregnant or breastfeeding, or intending to become pregnant during the study, including the OLE period, within 46 weeks (approximately 10.5 months) after the final dose of crovalimab
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
- Prior splenectomy
- History or presence of clinically significant electrocardiogram (ECG) abnormalities or cardiovascular disease
- Congenital or acquired complement deficiency
- Carriers of Neisseria meningitidis based on cultures from naso-pharyngeal swabs
Parts 2, 3 and 4 (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
- Splenectomy < 1 year before start of crovalimab.
Part 3 and 4 Arm B ( PNH patients only):
- Any evidence of sero-positive auto-immune connective tissue
diseases
- Any evidence of active inflammatory conditions
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method