A phase 1/2, prospective,randomized,double-blind, placebo-controlled study to evaluate safety,tolerability, Pk-PD & immunogenicity of single & multiple ascending doses of intravenously administered ZRC-NB-3224 in healthy adult participants & in patients with paroxysmal nocturnal hemoglobinuria

Phase 1

Registration Number: CTRI/2024/06/068347

Lead Sponsor: Zydus Lifesciences Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Open to Recruitment

Sex: Not specified

Target Recruitment: 0

Inclusion Criteria

Single ascending dose study:

1.Male and non-pregnant, non-lactating, female participants aged 18 to 50 years at screening (both inclusive).

2.Body mass index between 18.5 to 29.9 kg/m2 (both inclusive) and body weight =50 kg at screening.

3.Ability to communicate effectively with study personnel.

4.Be able to give consent for participation in the trial.

5.Healthy as determined based on personal medical/surgical history, physical examination, ECG, and laboratory assessment data during screening (within the clinically acceptable range).

6.Vaccinated against Neisseria meningitides with meningococcal group ACWY conjugate vaccine and meningococcal group B vaccine, Streptococcus pneumoniae, Haemophilus influenzae

7.Female participants with a history of sterility or at least 1 year menopause or use of long-acting non-hormonal contraceptive measures (e.g., intrauterine device). Those who are willing and able to continue contraception till study completion after administration of study treatment.

8.Men who agree to use adequate contraception methods during the study and are willing and able to continue contraception till study completion after administration of study treatment.

Multiple ascending dose study:

1.Male and non-pregnant, non-lactating female participants aged 18 to 65 years at screening (both inclusive).

2.Body mass index between 18.5 to 29.9 kg/m2 (both inclusive).

3.Treatment naïve patients (no history of complement-directed therapy) or stable regimen (dose and intervals) of any treatment (either eculizumab, ravulizumab, or any other treatment) for at least 3 months prior to screening and till study drug administration.

Exclusion Criteria

Single ascending dose study:

1.History of alcohol consumption or tobacco use or drug abuse within past 1 year of enrolment or participant currently consuming alcohol and/or tobacco products.

2.Presence or history of any of the disorder/disease within the past 3 months that might have an impact on the clinical trial as per the investigator’s discretion i.e., cardiovascular, nervous system, gastrointestinal, respiratory or any other major disorder.

3.Presence or suspicion of active viral, bacterial, fungal, or parasitic infection within 14 days before administration of the first dose of study drug.

4.Difficulty in donating blood.

5.Systolic blood pressure more than 140 mmHg or lesser than 100 mmHg and diastolic blood pressure more than 90 mmHg or less than 60 mmHg.

Multiple ascending dose study:

1.Known or suspected hereditary or acquired complement deficiency.

2.History of clinically significant arterial or venous thrombosis.

3.History of hematopoietic stem cell transplantation.

4.Active malignancy and/or history of malignancy in the past 5 years.

5.Prior splenectomy.

6.Treatment with another investigational product within 30 days.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Both Part I and II <br/ ><br> <br/ ><br>1)Incidence, severity, seriousness, and relationship of observed and self-reported adverse events (AEs) and severe AEs (SAEs). <br/ ><br>2)Safety assessments, including physical examination, vital sign recording (blood pressure, pulse rate, body temperature, and respiratory rate), continuous electrocardiogram (ECG; for part I only) monitoring, 12 lead ECG, injection site reaction, and clinical pathology laboratory measurements (i.e., hematology, biochemistry, coagulation profile, and urinalysisTimepoint: Baseline to end of study

Secondary Outcome Measures

Name	Time	Method
For Part 1 and Part 2 <br/ ><br> <br/ ><br>PK, PD and ImmunogenicityTimepoint: Baseline to end of study;For Part 2- PD effect of ZRC-NB-3224Timepoint: Baseline to end of study