None listed
Conditions
Brief summary
This is phase 1 first-in-human trial evaluating KP-104 to assess safety, tolerability, pharmacokinetics and pharmacodynamics. This study will be conducted in 2 parts - SAD and MAD with target of 64 healthy volunteers.
Interventions
The study will be conducted in 2 parts: Part 1 Single Ascending dose (SAD) and Part 2 Multiple Ascending dose (MAD).
Subjects in SAD will be enrolled in 1 of 5 cohorts (8 subjects per cohort).
Subjects in Cohorts 1 to 4 will be randomized in a 3:1 ratio (3 KP104: 1 placebo) to receive a single intravenously dose. Starting dose of 60 mg, increasing to 180mg, 360mg, 600mg
Subjects enrolled in Cohort 5 will be randomized in a 3:1 ratio (3 KP104: 1 placebo) to receive a single 180mg dose via subcuta
The study will be conducted in 2 parts: Part 1 Single Ascending dose (SAD) and Part 2 Multiple Ascending dose (MAD). Subjects in SAD will be enrolled in 1 of 5 cohorts (8 subjects per cohort). Subjects in Cohorts 1 to 4 will be randomized in a 3:1 ratio (3 KP104: 1 placebo) to receive a single intravenously dose. Starting dose of 60 mg, increasing to 180mg, 360mg, 600mg Subjects enrolled in Cohort 5 will be randomized in a 3:1 ratio (3 KP104: 1 placebo) to receive a single 180mg dose via subcutaneous injection. Dose escalation to the next cohort may occur after review by the Safety Monitoring Committee (SMC) of blinded safety, and available Pharmacokinetics and Pharmacodynamics data from all subjects in all cohorts through Day 15. Now, Up to 7 SAD cohorts are planned, comprising a total of approximately 56 subjects to be administered investigational product (IP) in Part 1 of the study (42 KP104 and 14 placebo). The first dose level to be studied will be 60 mg IV and the maximum dose level to be studied will be 900 mg IV. Two additional cohorts of subjects will receive 180 and 480 mg SC, respectively in order to assess the bioavailability of KP104. Part 2 ( MAD) of the study can only be initiated once SAD Cohort 2 has been completed and the Safety Monitoring Committee has approved dose escalation to SAD Cohort 3. Subjects in MAD will be enrolled to receive an initial intravenous loading dose of KP104 followed by one or more subsequent sub cutaneous maintenance doses of KP104. Subjects will be randomized in a 3:1 ratio (3 KP104: 1 placebo) to receive a single 180mg dose via sub-cutaneous injection. One initial intravenous loading dose of KP104 followed 1-2 weeks later by one or more SC maintenance doses spaced 1-2 weeks apart; the final number of doses and time between doses to be decided from data obtained in the preceding single dose study. The initial intravenous loading dose will be between 180 and 600mg. The subsequent subcutaneous maintenance doses will be between 180 and 360mg. Dose escalation to the next cohort may occur after review by the SMC of cumulative blinded safety, Pharmacokinetics and Pharmacodynamics data from all subjects in all cohorts through Day 15. Up to 3 MAD cohorts are planned, comprising a total of approximately 24 subjects to be administered IP. In each Cohort for both SAD and MAD, 2 sentinels will be enrolled and dosed in a 1:2 ratio ) ( 1KP104: 1 placebo), and the rest of cohort ( ROC) (6 subjects) can be enrolled following a 7 day- observation period of the sentinels.
Sponsors
Kira Pharmaceuticals
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Is male or female, age 18 to 55 years, inclusive, at Screening 2. Weight of > 40 kg and < 120 kg at Screening 3. In good general health, determined by no clinically significant findings in the opinion of the Investigator from medical history, physical examination, 12-lead electrocardiogram (ECG), clinical laboratory findings, and vital signs at Screening and Check-in 4. Hemoglobin, hematocrit, white blood cell count, absolute neutrophil count, and platelet count results within the normal range at the Screening Visit; subjects with Gilbert’s disease with associated abnormalities of liver function tests are eligible for enrollment. Tests may be repeated at the discretion of the Investigator to confirm abnormalities. 5. Creatinine clearance based on the Cockcroft-Gault equation of equals to 80 ml/min 6. Females of childbearing potential and males must practice effective contraception from Screening until 28 days after the EOS visit. 7. Females of childbearing potential must have a negative pregnancy test at Screening and within 24 hours prior to dosing of study drug; for post-menopausal subjects, a blood sample will also be tested for follicle stimulating hormone to confirm post-menopausal status. 8. Males must agree to not donate sperm for 90 days following the last dose of IP 9. Must provide evidence of prior vaccination against Neisseria meningitidis, Streptococcus pneumoniae, and Hemophilus influenzae at least 2 weeks prior to their initial dose of IP (subjects receiving vaccination during Screening and less than 2 weeks prior to their initial dose of IP are required to receive treatment with appropriate antibiotic prophylaxis until 2 weeks after vaccination); if unvaccinated and they decline vaccination, must agree to self-administer oral antibiotic prophylaxis for a total of 6 weeks following their last dose of IP 10. Able to provide Informed Consent 11. Willing and able to comply with this protocol and be available for the entire duration of the study
Exclusion criteria
1. Any clinically significant underlying illness in the opinion of the Investigator 2. Any history or sign of significant chronic active or recurrent infection, or screening laboratory evidence consistent with a significant chronic active or recurrent infection requiring treatment with antibacterials, antivirals, or antifungals 3. Treatment of any infection with IV (within 30 days of Screening) or oral (within 14 days of Screening) antibacterials, antivirals, or antifungals 4. History of clinically significant hematologic or bone marrow disease or blood dyscrasias 5. History of meningococcal infection 6. History of tuberculosis 7. History of asplenia (functional or anatomical) 8. Prior exposure to KP104 9. Known allergy to penicillin antibiotics or history of allergy or contraindication to required prophylactic antibiotic therapy to be used during the study 10. Known or suspected complement deficiency during screening 11. Positive serology for HBV, HCV or HIV at Screening 12. History of drug or alcohol abuse within 1 year of Screening in the opinion of the investigator, or a positive test for drugs of abuse or alcohol at Screening or Check-in 13. Received any type of live attenuated vaccine < 1 month prior to Screening or is planning to receive any such live attenuated vaccine over the course of the study 14. Use of any prescription or OTC medications including food supplements and herbal medications (e.g. St. John’s wort), with the exception of contraceptive medications and as needed (prn) paracetamol (not exceeding 2 grams/day) within 7 days prior to IP administration 15. History of malignancy, except adequately treated basal cell carcinoma or in situ carcinoma of the uterine cervix 16. History of drug allergy or drug hypersensitivity, or intolerance of IV or SC injections 17. Smoking greater than 10 cigarettes per week in the 3 months prior to IP administration 18. History of excessive bleeding following trauma or medical/dental procedures 19. Any female who is pregnant or breastfeeding, or any female who is planning to become pregnant during the study and follow-up period 20. Any condition that, in the investigator’s opinion, may compromise study participation, present a safety risk to the subject, or may confound the interpretation of the study results 21. A QT duration corrected for heart rate by Fridericia's formula (QTcF) > 450 millisecond (msec) for males or > 470 msec for females based on either single or averaged QTcF values of triplicate ECGs obtained over a 3-minute interval (at Screening). 22. Currently enrolled in another investigational device or drug study, or less than 30 days have passed since ending another investigational device or drug study
Outcome results
None listed