A Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of NM-101 in Healthy Male and Female Subjects

NM-101-01-2022

This is a Phase I, double-blind, randomised, two-part, single-ascending dose (Part 1) and multiple-ascending dose (Part 2) study of NM-101 in healthy males and healthy females of non-childbearing potential

2023-05-10

2024-05-30

2024-06-14

Not yet recruiting

Early phase I

56

Inclusion Criteria: Informed Consent and Compliance 1. Must provide written informed consent 2. Must be willing and able to communicate and participate in the whole study Demographics and Contraception 3. Aged 18 to 65 years inclusive at the time of signing informed consent 4. Must agree to adhere to the contraception requirements Baseline Characteristics 5. Healthy males or WONCBP 6. Body mass index (BMI) of 18.0 to 32.0 kg/m2 as measured at screening Other 7. Must have received at least 2 doses of a COVID-19 vaccine Exclusion Criteria: Medical/Surgical History and Mental Health 1. Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients 2. History of allergic or anaphylactic reactions to humanised or other therapeutic monoclonal antibodies or to any of the excipients of NM-101 3. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active 4. History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator 5. Undergone a lumbar puncture within 6 weeks before Day 1 (Part 2 only) 6. Medical history or evidence of mass occupying lesion in brain or spinal cord or history of spinal cord injury, which could preclude the procedure of lumbar puncture and CSF collection (Part 2 only) 7. Evidence or history of clinically significant back pain, back pathology and/or back injury (e.g. degenerative disease, spinal deformity or spinal surgery) that may predispose to complications or technical difficulties in the conduct of a lumbar puncture (Part 2 only) Physical Examination 8. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening Diagnostic Assessments 9. Evidence of current SARS-CoV-2 infection 10. History of an infection requiring treatment within 14 days of first dose of the IMP 11. A history of any ongoing, chronic or recurrent infectious disease, herpes, or evidence of tuberculosis infection as defined by a positive QuantiFERON® TB Gold test at screening 12. Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator 13. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results 14. Females of childbearing potential including those who are pregnant or lactating (all female subjects must have a negative highly sensitive serum pregnancy test) Prior Study Participation 15. Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1, or less than 5 elimination half-lives prior to Day 1, whichever is longer 16. Subjects who have previously been administered IMP in this study. Subjects who have taken part in Part 1 are not permitted to take part in Part 2 and vice versa 17. Subjects who report to have previously received NM-101 (formerly known as OPN-305) 18. Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood Prior and Concomitant Medication 19. Subjects who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies (other than up to 4 g of paracetamol per day or HRT) in the 14 days before first IMP administration. Exceptions may apply, as determined by the investigator 20. Subjects who have had a vaccine (including COVID-19 vaccine) within 28 days before first dose 21. Have taken non-steroidal anti-inflammatory drugs or other drugs that affect coagulation or platelet function within 14 days prior to scheduled lumbar puncture (Part 2 only) Lifestyle Characteristics 22. History of any drug or alcohol abuse in the past 2 years 23. Regular alcohol consumption in males \>21 units per week and in females \>14 units per week 24. A confirmed positive alcohol breath test at screening or admission 25. Current smokers and those who have smoked within the last 12 months 26. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission 27. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months 28. Confirmed positive drugs of abuse test result Other 29. Male subjects with pregnant or lactating partners 30. Travelled to an area where there is risk of malaria within the past year unless adequate precautions were taken 31. Subjects who are, or are immediate family members of, a study site or sponsor employee 32. Failure to satisfy the investigator of fitness to participate for any other reason

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2023-03-30