Cutaneous leishmaniasis Infections and Infestations Cutaneous leishmaniasis
Conditions
Interventions
Participants will be split into four groups of eight to receive a single subcutaneous (SC) dose of CpG ODN D35 (six subjects) or placebo (two subjects). Each group evaluates a different dose strength
Sponsors
Drugs for Neglected Diseases Initiative
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Male healthy subjects 18 to 50 years old at the time of obtaining the informed consent 2. Body weight =60 kg to =90 kg, BMI 18 to 30.1 kg/m². BMI = body weight (kg) / [height (m)]² 3. Provision of written informed consent to participate as shown by a signature on the participant information sheet and consent form, after reading the information sheet and consent form, and after having the opportunity to discuss the trial with the Investigator or his/her delegate 4. Normal blood pressure: systolic blood pressure between =100 and =140 mmHg, diastolic blood pressure =90 mmHg, measured after 10 min rest in a supine position at Screening, admission, and pre-dose 5. A resting heart rate (HR) between =45 and =90 bpm measured after 10 min rest in a supine position at Screening, admission, and pre-dose 6. ECG recording without clinically significant abnormality, including a QTcF measure of =450 msec 7. Male participant (and partner of childbearing potential) willing to use a highly effective method of contraception, if applicable (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the participant) from first dose until 3 months after the last dose of IMP 8. No clinically significant history of previous allergy/sensitivity to CpG ODN D35 or any of the excipients contained within the IMP(s) 9. No clinically significant abnormal test results for serum biochemistry, haematology and/or urine analyses within 28 days before the first dose administration of the IMP 10. Participant with a negative urinary drugs of abuse (DOA) screen (including alcohol/cotinine) test results, determined within 28 days before the first dose administration of the IMP (N.B.: a positive test result may be repeated at the Investigator’s discretion) 11. Participant must be available to complete the study (including all follow-up visits) 12. Participant must satisfy an Investigator about his fitness to participate in the study
Exclusion criteria
Exclusion criteria: 1. Behavioural, cognitive, or psychiatric disease that in the opinion of the Investigator affects the ability of the participant to understand and cooperate with the study protocol 2. History of clinically significant cardiovascular, renal, hepatic, neurological (especially seizures), immunological, psychiatric, myopathies, bleeding tendency, respiratory and particularly GI disease, especially peptic ulceration and chronic gastritis, GI bleeding, ulcerative colitis, Crohn’s disease or irritable bowel syndrome, as judged by the Investigator 3. Individual or family history of pre-existing autoimmune or antibody-mediated diseases including (but not limited to): systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, type 1 diabetes mellitus, auto-immune thyroiditis, Basedow syndrome, autoimmune thrombocytopenia; or proteinuria (greater than trace protein on urine dipstick testing) 4. History of allergy, hay fever, intolerance or photosensitivity to any drug or have a history of serious allergy, asthma, allergic skin rash or sensitivity to any drug 5. Subjects who are taking, or have taken, any prescribed or over-the-counter drug (including non-steroidal anti-inflammatory drugs (NSAID)) in the 28 days or 5 half-lives (whichever is longer) before IMP administration. Administration of up to 3 g of paracetamol per day within 7 days of IMP administration is allowed 6. Subjects who have received any prophylactic vaccine (including COVID-19 vaccine) or immunization within the last 28 days or use of corticosteroids or immunosuppressive drugs within 28 days of IMP administration 7. Subjects with febrile illness or infectious illness within 2 weeks of IMP administration 8. Subjects with positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) and or human immunodeficiency virus (HIV) tests results at Screening 9. Positive RT-PCR COVID-19 test at admission 10. Donation or loss of greater than 500 ml of blood within the previous 3 months prior to IMP administration 11. Major surgery within 12 weeks prior to Screening 12. Subjects who are known or suspected alcohol abusers (more than 14 units of alcohol per week, one unit = 8 g or about 10 ml of pure alcohol). Positive alcohol test at Screening or admission 13. Demonstrating excess caffeine/xanthine consumption (more than 6 cups of coffee or equivalent a day) 14. History of use of drugs of abuse in the past 2 years 15. Subjects who do not have suitable veins for multiple venepunctures/cannulation 16. Subjects who have any clinical condition or prior therapy which, in the opinion of the Investigator, could jeopardize the safety or rights of a volunteer participating in the trial or would render them unable to comply with the protocol 17. Participation in a non-marketed drug clinical study within 3 months or five half-lives (whichever is longer) or a marketed drug clinical study within 30 days or five half-lives (whichever is longer) before the first dose of IMP (washout period between studies is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study) 18. Subjects who are study site employees, or immediate family members of a study site or sponsor employee 19. Inability to communicate well with the Investigators (i.e., language problem, poor mental development or impaired cerebral function) 20. Users of nicotine products i.e., current smokers or ex-smokers who have smoked within th
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability of CpG ODN D35 after a single dose measured by: 1. Frequency of adverse events (AEs), based on the clinical judgement of the investigator, occurring from first dosing up to post-study follow-up visit (13 to 14 days post dose) 2. Frequency of participants reporting AEs, based on the clinical judgement of the investigator, from first dosing up to post-study follow-up visit (13 to 14 days post dose) 3. Causality of AEs, based on the clinical judgement of the investigator, occurring from first dosing up to post-study follow-up visit (13 to 14 days post dose). The possible relationship between the AE and the study drug will be quoted as follows: 3.1. Definitely related. The AE and administration of the study agent are related in time, and a direct association can be demonstrated. 3.2. Probably related. The AE and administration of the study agent are reasonably related in time, and the AE is more likely explained by the study agent than other causes. 3.3. Possibly related. The AE and administration of the study agent are reasonably related in time, and the AE can be explained equally well by causes other than the study agent. 3.4. Probably not related. A potential relationship between the study agent and the AE could exist (i.e., the possibility cannot be excluded), but the AE is most likely explained by causes other than the study agent. 3.5. Not related. The AE is clearly explained by another cause not related to the study agent. 4. Severity of AEs assessed based on the clinical judgement of the investigator, occurring from first dosing up to post-study follow-up visit (13 to 14 days post dose). The severity of the AEs will be determined using the following grading scale: Guidance for Industry. Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. U.S. Department of Health and Human Services Food and Drug Administration Centre for Biologics Evaluation and Research. September 2007. | — |
Secondary
| Measure | Time frame |
|---|---|
| The following PK parameters will be derived from plasma CpG ODN D35 concentrations (additional parameters may be derived, if applicable) in samples taken at the following timepoints: Day 1: pre-dose, 10 min, 20 min, 30 min, 45 min, 1 h, 2 h & 4 hr post-dose: 1. Cmax (ng/ml): observed maximum plasma concentration 2. Tmax (h): first time to reach Cmax 3. ?z (1/h): apparent first-order terminal elimination rate constant 4. t1/2 (h): plasma elimination half-life 5. AUClast (ng.h/ml): AUC from 0 to the time of the last quantifiable concentration 6. AUCall (ng.h/ml): AUC from 0 to the time of the last observation, regardless of whether the last concentration is measurable or not 7. AUC0-24 (ng.h/ml): AUC over 24 hours 8. AUC0-inf (ng.h/ml): AUC extrapolated to infinity 9. AUC% extrapolated (%): residual area | — |
Countries
United Kingdom, Wales
Contacts
Public ContactSeverine Blesson
Outcome results
None listed