Healthy volunteers. Intended indication for CR9114 monoclonal antibody under development: prevention (prophylaxis) of influenza A and B infections in adults. Infections and Infestations
Conditions
Interventions
Following a screening visit, participants will be admitted to the clinical trial site for study drug administration, participants in part B will also receive a single viral challenge with influenza A/
Sponsors
Leyden Laboratories B.V.
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1. Written informed consent signed and dated by the participant and the PI/investigator obtained before any assessment is performed 2. Aged between 18 and 55 years old on the day prior to signing the consent form 3. Total body weight =50 kg and BMI =18 kg/m² and =35 kg/m² 4. In good health with no history or current evidence of clinically significant medical conditions 5. Females of non-childbearing potential or females of childbearing potential with negative pregnancy test and use of highly effective contraceptive method from 2 weeks before first study visit until 28 days after last IMP dose 6. Serosuitable for the challenge agent (Part B only): serology indicating susceptibility to influenza A/H1N1 challenge virus
Exclusion criteria
Exclusion criteria: 1. History of or currently active symptoms of upper or lower respiratory tract infection within 4 weeks prior to first study visit 2. Any clinically significant or active disease that may interfere with study participation per PI or investigator 3. Current smoker, or ex-smoker who ceased within the past 6 months, or cumulative smoking history =10 pack-years including significant vaping history 4. Females who are breastfeeding, have been pregnant within 6 months prior to the study 5. Lifetime history of anaphylaxis or severe allergic reaction, or significant food or drug intolerance in the last 12 months 6. Significant anatomical nasal abnormality, clinically significant epistaxis within 3 months 7. Within 180 days prior to viral challenge: receipt of influenza vaccine or antiviral medication for influenza or have confirmed influenza illness 8. Receipt of any vaccination within 4 weeks prior to first IMP dose, or intention to receive vaccination before end of follow-up 9. Receipt of any investigational drug within 3 months prior to first IMP dose 10. Immunomodulatory drugs or systemic or intranasal corticosteroids within 6 months prior to first IMP dose, systemic antivirals within 4 weeks, or chronic intranasal medications within 3 months 11. Positive HIV, hepatitis B, or hepatitis C test 12. Positive drug screen on admission
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A — Primary endpoint: Occurrence of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), from first IMP administration up to the last follow-up visit (Day 28) Part B — Primary endpoint: Area under the viral load-time curve (VL-AUC) of influenza A/H1N1 challenge virus, measured by qRT-PCR on nasal samples collected during the post-challenge quarantine period from Day 1 to Day 8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Part A — Secondary Endpoints: 1. PK: CR9114 mAb concentrations in serum and nasosorption (epithelial lining fluid) samples at protocol-specified timepoints 2. Immunogenicity: Presence of anti-drug antibodies (ADAs) in serum Part B — Secondary Endpoints: Efficacy endpoints are assessed during the post-challenge quarantine period from Day 1 to Day 8 Efficacy — Viral load: 1. VL-AUC of influenza A challenge virus, measured by viral culture 2. Peak VL, time to peak VL, time to resolution of VL, measured by qRT-PCR or viral culture Efficacy — Infection incidence: 3. Laboratory-confirmed influenza infection, measured by qRT-PCR or culture, with and without specified symptoms Efficacy — Symptoms: 4. Total Symptom Score (TSS) AUC, peak TSS, peak daily symptoms and time to symptoms resolution Safety: 5. TEAEs (including SAEs) from first IMP administration through Day 28follow-up 6. SAEs related to challenge agent from Day 0 through Day 28 follow-up 7. Concomitant medication use from Day 0 through Day 28 follow-up PK and Immunogenicity: 8. CR9114 mAb concentrations in serum and nasosorption samples at protocol-specified timepoints 9. Presence of ADAs in serum | — |
Countries
England, United Kingdom
Contacts
Public ContactJoana;Joana Meireles;Meireles
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Outcome results
None listed