Healthy volunteers Other
Conditions
Interventions
This is a Phase I, randomized, open-label, single-dose, parallel-group study in healthy male andfemale participants.
Participants will be randomized in a 1:1 ratio to receive a single SC dose of sefax
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to participate and willing to give written informed consent and to comply with the study restrictions according to International Council for Harmonisation (ICH) and local regulations. 2. Healthy male and female participants, 18 to 55 years of age, inclusive, at the time of signing the Informed Consent Form (ICF). 3. Body mass index (BMI) of 18.5 to 32.0 kg/m², inclusive. 4. Body weight within 55 to 110 kg, inclusive. 5. Male and/or female participants: The reliability of sexual abstinence for enrollment eligibility for male and/or female participants needs to be evaluated in relation to the duration of the clinical study and the preferred, usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, or postovulation methods) and withdrawal are not acceptable methods. a) Female participants: Female participants are eligible to participate if not pregnant, not breastfeeding. b) Male participants: no contraception requirements. 6. Vaccination against Neisseria meningitidis <3 years prior to initiation of study treatment. Vaccination must include coverage of serogroups A, C, W, and Y. Vaccination against serogroup B should be administered according to local guidelines and national availability. A participant’s vaccination status should be maintained in accordance with the most current local guidelines or standard of care. If vaccination is required during screening, the vaccination must be completed at least 2 weeks prior to administration of sefaxersen. 7. Vaccination against Streptococcus pneumoniae administered within the recommended timeframe according to the most current local guidelines. If vaccination is required during screening, the vaccination must be completed at least 2 weeks prior to administration of sefaxersen. 8. Vaccination against Haemophilus influenzae B according to national vaccination recommendations for patients receiving complement inhibitors. If vaccination is required during screening, the vaccination must be completed at least 2 weeks prior to administration of sefaxersen.
Exclusion criteria
Exclusion criteria: 1. A history of clinically significant gastrointestinal, renal, hepatic, cardiovascular, allergic/immunologic, pulmonary, hematologic, neurologic, psychiatric, metabolic, or endocrine disease or treatment of which might interfere with the conduct of the study or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study including, but not limited to, any major illness within 1 month before the screening examination or any febrile illness within 1 week prior to study treatment administration. 2. History or evidence of any medical conditions potentially altering the absorption, distribution, metabolism, or elimination of drugs as judged by the Investigator (or designee). 3. History or presence of clinically significant ECG abnormalities, QT interval corrected for heart rate using the Fridericia’s correction factor (QTcF) >450 ms for male or >470 ms for female participants, or clinically significant cardiovascular disease. 4. History of malignancy within 90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer. 5. History of complement disorder. 6. Systolic blood pressure 100 beats per minute or <50 beats per minute, at screening. 8. Participants who were exposed within 2 weeks prior to enrollment to an individual who tested positive for severe acute respiratory syndrome coronavirus 2 should be carefully and comprehensively evaluated as per usual medical practice and institutional guidance before enrollment. The Investigator should assess the benefit-risk ratio for each participant. 9. Any clinically significant history of hypersensitivity or allergic reactions, either spontaneous or following drug administration, or exposure to food or environmental agents. 10. History of hypersensitivity to any of the excipients in the formulation of sefaxersen. 11. History of hypersensitivity, or contraindication to, any of the vaccinations required for inclusion to this study (Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae B). 12. Prior treatment with any oligonucleotide or small interfering ribonucleoside. 13. Use of glucocorticoids, complement inhibitors, and other immunosuppressive medications is prohibited within 30 days or within 5 times the elimination half-life, whichever is longer, prior to Day 1. 14. Participation in an investigational medicinal product (IMP) or medical device study within 30 days before study treatment administration or within 5 times the elimination half-life, whichever is longer. 15. Donation of blood or blood products for transfusion over 500 mL or receipt of blood or blood products and/or significant blood loss within 3 months prior to study treatment administration and for the duration of the study. 16. Clinically significant abnormalities (as judged by the Investigator) in laboratory test results (including complete blood count, chemistry panel, and urinalysis). 17. Platelet count < lower limit of normal. 18. Positive result on hepatitis B virus (HB
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Geometric mean ratio and 90% CI (injection device vs. vial and syringe) for the primary PK parameters: AUC0-inf and Cmax derived using a non-compartmental method. If AUC0-inf cannot be estimated with sufficient accuracy, AUC0-t will be used instead. From the time of IP administration until end of study. | — |
Secondary
| Measure | Time frame |
|---|---|
| From the time of IP administration until end of study: 1. AUC0-t, (AUC0-168h and any other additional partial AUCs if deemed necessary), AUC0-last, AUC%extrap, tmax, CL/F, Vz/F, ?z, and t1/2 derived using a non-compartmental method. 2. Incidence and severity (CTCAE grading) of ISRs: 2.1. Incidence, severity, and nature of adverse events and serious adverse events. 2.2. Incidence of abnormal laboratory findings and abnormal vital signs. 2.3. Incidence of abnormal electrocardiogram assessments. 3. Percent change from baseline in plasma complement factor B levels. | — |
Countries
England, United Kingdom
Contacts
Public ContactSarah Casey
Outcome results
None listed