Paroxysmal Nocturnal Hemoglobinuria (PNH)
Conditions
Brief summary
The purpose of this study is to evaluate safety, tolerability, immunogenicity, pharmacokinetics, pharmacodynamics, and efficacy of LP-005 in healthy volunteers. The study will be conducted in 2 parts: Part 1, the single ascending dose (SAD) is the first in human (FIH) study of LP-005 and Part 2, multiple ascending dose (MAD).
Interventions
BIOLOGICALLP-005 Dose 1 (Single)
A single dose of LP-005 (Dose 1) was administered intravenously.
BIOLOGICALLP-005 Dose 2 (Single)
A single dose of LP-005 (Dose 2) was administered intravenously.
BIOLOGICALLP-005 Dose 3 (Single)
A single dose of LP-005 (Dose 3) was administered intravenously.
BIOLOGICALLP-005 Dose 4 (Single)
A single dose of LP-005 (Dose 4) was administered intravenously.
BIOLOGICALLP-005 Dose 5 (Single)
A single dose of LP-005 (Dose 5) was administered intravenously.
BIOLOGICALLP-005 Dose 6 (Single)
A single dose of LP-005 (Dose 6) was administered intravenously.
BIOLOGICALPlacebo (Single)
A single dose of placebo was administered intravenously.
BIOLOGICALLP-005 Dose 7 (Multiple)
LP-005 (Dose 7) was administered multiple times intravenously.
BIOLOGICALLP-005 Dose 8 (Multiple)
LP-005 (Dose 8) was administered multiple times intravenously.
BIOLOGICALLP-005 Dose 9 (Multiple)
LP-005 (Dose 9) was administered multiple times intravenously.
BIOLOGICALPlacebo (Multiple)
Placebo was administered multiple times intravenously.
Sponsors
Longbio Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy males or females aged 18 through 50 years 2. Male subjects with a weight of ≥50 kg, female subjects with a weight of ≥45 kg, and BMI between 19.0 and 26.0 kg/m² (inclusive). 3. Vaccination: Meningococcal Conjugate Vaccine, Serogroups A, C, W, Y (MPV-ACYW) meningococcal conjugate vaccine and Streptococcus pneumoniae vaccine should be given 14 days or more before randomisation. 4. Male subjects and their partners or female subjects must agree to use one or more non-pharmaceutical contraceptive methods (such as total abstinence, condoms, Iuds, partner ligation, etc.) during the trial period and for 6 months after the trial, and do not plan to donate sperm or eggs. 5. The subjects fully understand the purpose, nature, method and possible adverse reactions of the experiment, and voluntarily participate in the experiment and sign the informed consent. 6. The subjects were able to communicate well with the researchers and complete the study according to the protocol.
Exclusion criteria
1. Participants who are immunocompromised or have one of the following underlying diseases: anatomic absence of spleen (including sickle cell disease); congenital complement component deficiencies (complement component 3 and complement component 4). 2. Any history of Neisseria gonorrhea, meningitis infection, and Guillain-Barré syndrome. 3. Contraindications to meningococcal vaccination (previous medical history such as epilepsy or other brain disorders). 4. Presence or suspicion of active viral, bacterial, fungal, or parasitic infection, including herpes, shingles, or cold sores, within 14 days prior to screening. 5. History of unexplained recurrent infections, or use of systemic antibiotics within 90 days prior to dosing. 6. Malignancy or history of malignancy, except non-melanoma skin cancer cured for more than 3 years. 7. Positive HIV test (HIV-Ab), positive hepatitis B virus (HBV) test (HBsAg), positive hepatitis C virus (HCV), positive anti-syphilis helix-specific antibodies. 8. Participation in a clinical trial of any other drug within 3 months prior to screening or within 5 half-lives of other clinical trial drugs (selecting the longer time period). 9. Women who are pregnant, breastfeeding, or at risk of pregnancy. 10. Any condition deemed unsuitable for study participation by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | Observation for 78 days after administration | Number of subjects with treatment-related Treatment Emergent Adverse Events (TEAEs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum concentration (Cmax) of LP-005 | Observation for 78 days after administration | The maximum concentration of LP-005 in the bloodstream after administration. |
| Elimination half-life (t1/2) of LP-005 | Observation for 78 days after administration | The time required for the concentration of LP-005 in the bloodstream to decrease by half. |
| Area under the concentration-time curve (AUC0-t) of LP-005 | Observation for 78 days after administration | The area under the concentration-time curve (AUC) from time zero to the last chosen time point represents the integral of the drug concentration in the bloodstream over the specified duration. |
| Time to peak concentration (Tmax) of LP-005 | Observation for 78 days after administration | The time when the blood drug concentration reaches its peak after a single dose of medication. |
| Assessment of immunogenicity | Observation for 78 days after administration | The proportion of anti drug antibody (ADA) positive subjects at different detection time points. |
| Assessment of complement C5 activity | Observation for 78 days after administration | Evaluate complement C5 hemolytic activity and serum concentration of C5 changes from baseline at various time points of assessment. |
| Assessment of complement C3b activity | Observation for 78 days after administration | Evaluate C3b deposition on red blood cells and serum concentration of C3b changes from baseline at various time points of assessment. |
| Apparent clearance rate (CL/F) of LP-005 | Observation for 78 days after administration | The ratio of drug clearance to drug concentration, represents the apparent clearance of a drug after administration, adjusted for bioavailability. |
Countries
China
Outcome results
None listed