Neurological- and autoimmune disorders
Conditions
Interventions
ANX105, Cohort 1: single doses of 1 mg/kg, cohort 2: single
Sponsors
Annexon, Inc.
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all the following criteria apply: Age 1. Participants must be 18 (or the legal age of consent in the jurisdiction in which the study is taking place) to 55 years of age inclusive, at the time of signing the informed consent. Type of Participant and Disease Characteristics 2. Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, and laboratory tests. Weight 3. Body weight within the range 45 kg to 110 kg and body mass index (BMI) within the range >=18.0 kg/m2 to <=33.5 kg/m2 (inclusive) at the Day -1 visit. Sex and Contraceptive/Barrier Requirements 4. Participants who are male or female Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Male participants: Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the dose: • Refrain from donating fresh unwashed semen Plus, either: o Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR o Must agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant b. Female participants: • A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: o Is a woman of nonchildbearing potential (WONCBP) as defined in protocol Appendix 4: Contraceptive and Barrier Guidance. OR o Is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of <1%, as described in protocol Appendix 4: Contraceptive and Barrier Guidance during the study intervention period and for at least 90 days after the dose. The Investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of the study intervention. • A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention, see Protocol Section 8.2.7: Pregnancy Testing. o If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. • Additional requirements for pregnancy testing during and after study intervention are outlined in protocol Section 8.2.7: Pregnancy Testing • The Investigator is responsible for the review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with early undetected pregnancy. Informed Consent 5. Capable of giving signed informed consent as described in protocol Section 10.1.3 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and this protoco
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1. History or presence of clinically relevant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders. 2. History or presence of conditions capable of significantly altering the disposition of drugs that constitute a risk when taking the study intervention or interfere with the interpretation of data. 3. History of any autoimmune disease (eg, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, autoimmune vasculitis, Guillain-Barré syndrome, autoimmune hepatitis, or psoriasis). 4. History of meningitis or septicemia. 5. Clinically significant infection (eg, viral, bacterial, fungal, or mycobacterial), with the exception of onychomycosis, within 30 days prior to Day 1 that required medical intervention (not including antibiotic prophylaxis). 6. Known genetic deficiencies of the complement cascade system or immunodeficiency. 7. Abnormal blood pressure as determined by the Investigator. 8. Significant allergies to humanized monoclonal antibodies. 9. Clinically significant drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A [IgA] dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis). 10. History or presence of any malignancy (excluding basal cell carcinoma). 11. Liver disease or liver function tests such as alanine transaminase (ALT) or aspartate transaminase (AST) >1.5xULN (upper limit of normal), serum total bilirubin (isolated bilirubin >1.5xULN is acceptable if total bilirubin is fractionated and direct bilirubin 120 msec; heart rate 450 msec for male participants and >470 msec for female participants. The ECG may be repeated twice with a manually measured QTcF and the average of 3 manually measure QTcF values will be obtained to determine the participant*s eligibility. • PR interval >200 msec and any other clinically relevant abnormality. 14. Abnormalities in the lumbar spine were previously known . 15. History of clinically significant back pain, back pathology, and/or back injury (for example, degenerative disease, spinal deformity, or spinal surgery) that may predispose the participant to complications or technical difficulty with a lumbar puncture. 16. Evidence or history of significant active bleeding or coagulation disorder that affects coagulation or platelet function within 14 days prior to lumbar catheter insertion. 17. Allergy to lidocaine (Xylocaine®) or its derivatives. 18. Medical or surgical conditions for which lumbar puncture is contraindicated. 19. History or presence of anemia or neutropenia. Prior/Concomitant Therapy 20. Past or intended use of over-the-counter medication including herbal medications within 7 days prior to Day 1 . 21. Past or intended use of prescription medication within 14 days prior to
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of treatment-emergent adverse events (TEAEs), laboratory abnormalities, 12 lead electrocardiogram (ECG) abnormalities, and interval measurements, and vital sign measurement, after a single dose. | — |
Secondary
| Measure | Time frame |
|---|---|
| • Inhibition of complement activity for example as measured by serum total hemolytic complement (CH50) over time • Change from baseline and time course of unbound C1q in serum • Unbound C1q in cerebrospinal fluid (CSF) • Serum ANX105 concentrations over time • Serum unbound ANX105 single dose PK parameters • CSF unbound ANX105 concentrations | — |
Countries
Netherlands
Outcome results
None listed