A Study of Single and Multiple Dose Administration of LP-001 in Healthy Subjects

A Phase I Clinical Study Evaluating the Safety, Tolerability, and Pharmacokinetics of LP-001 Injection in Healthy Subjects Following Single and Multiple Doses

The purpose of this study is to evaluate safety, tolerability, immunogenicity, pharmacokinetics, pharmacodynamics, and efficacy of LP-001 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-001 and Part 2, multiple ascending dose (MAD).

Study Overview

• Status: Active, not recruiting
• Conditions: Myelodysplastic Syndrome (MDS)
• Intervention / Treatment: Biological: LP-001 Dose 1 (Single); Biological: LP-001 Dose 2 (Single); Biological: LP-001 Dose 3 (Single); Biological: LP-001 Dose 4 (Single); Biological: LP-001 Dose 5 (Single); Biological: LP-001 Dose 6 (Single); Biological: Placebo (Single); Biological: LP-001 Dose 7 (Multiple); Biological: LP-001 Dose 8 (Multiple); Biological: Placebo (Multiple)

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Shanghai Public Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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. Male subjects and their partners, or female subjects, must agree to use one or more non-pharmacological contraceptive measures during the trial and up to 6 months after the end of the trial (such as complete abstinence, condoms, intrauterine devices, partner sterilization, etc.), and should have no plans for sperm or egg donation.
4. The upper limits for hemoglobin (Hb) and hematocrit (HCT) are 165 g/L and 49%, respectively, for males, and 150 g/L and 45%, respectively, for females.
5. Subjects have a full understanding of the trial's purpose, nature, methods, and potential adverse reactions, voluntarily agree to participate in the trial, and sign the informed consent form.
6. Subjects can communicate effectively with the researchers and can comply with the study protocol as specified.

Exclusion Criteria:

1. Family history of early-onset coronary artery disease, including first- or second-degree relatives diagnosed with coronary heart disease or angina before the age of 50; any family history of hematological disorders, such as thrombosis or increased clotting risk, or any family history of deep vein thrombosis, pulmonary embolism, stroke, hemolytic anemia, or hemoglobinopathies; family history of hypertension. Alternatively, the subject has a personal medical history of the aforementioned conditions.
2. Presence of liver or kidney diseases or conditions affecting drug absorption, distribution, metabolism, or excretion, including other medical situations such as surgical procedures, trauma, etc. that may interfere with these processes.
3. Diagnosed with malignant tumors or having a history of malignant tumors, excluding non-melanoma skin cancer cured for more than 3 years.
4. HIV testing positive (HIV-Ab), hepatitis B virus (HBV) testing positive (HBsAg or HBcAb), hepatitis C virus (HCV) positive (HCV-RNA), and specific antibodies for syphilis positive, excluding positive results caused by immunization.
5. Abnormal vital signs (reference normal range: sitting systolic blood pressure 90-139 mmHg, diastolic blood pressure 60-89 mmHg, pulse rate 60-100 beats/min; body temperature 35.4-37.7°C) or abnormal electrocardiogram (QTcB≥450 ms), or clinically significant abnormalities in physical examination, laboratory tests, and abdominal ultrasound (as judged by the clinical research doctor).
6. Clear history of drug allergy or specific hypersensitivity reactions (asthma, urticaria, allergic rhinitis, eczematous dermatitis); known allergies to the investigational drug and excipients, or allergies to similar drugs; individuals intolerant to subcutaneous injections or with a history of fainting during needle procedures.
7. Use of erythropoiesis-stimulating agents or treatment with other biologics within the six months prior to screening.
8. Participation in any other drug clinical trial within the 3 months prior to screening or within 5 half-lives of any investigational drug from other clinical trials (selecting the longer time period).
9. Pregnant or lactating women or women with the possibility of becoming pregnant.
10. Any condition deemed unsuitable for participation in the study by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: LP-001 Dose 1 (Single); Single dose administration of LP-001 with dose 1	Biological: LP-001 Dose 1 (Single); A single dose of LP-001 (Dose 1) was administered subcutaneously.
Experimental: Cohort 2: LP-001 Dose 2 (Single); Single dose administration of LP-001 with dose 2	Biological: LP-001 Dose 2 (Single); A single dose of LP-001 (Dose 2) was administered subcutaneously.
Experimental: Cohort 3: LP-001 Dose 3 (Single); Single dose administration of LP-001 with dose 3	Biological: LP-001 Dose 3 (Single); A single dose of LP-001 (Dose 3) was administered subcutaneously.
Experimental: Cohort 4: LP-001 Dose 4 (Single); Single dose administration of LP-001 with dose 4	Biological: LP-001 Dose 4 (Single); A single dose of LP-001 (Dose 4) was administered subcutaneously.
Experimental: Cohort 5: LP-001 Dose 5 (Single); Single dose administration of LP-001 with dose 5	Biological: LP-001 Dose 5 (Single); A single dose of LP-001 (Dose 5) was administered subcutaneously.
Experimental: Cohort 6: LP-001 Dose 6 (Single); Single dose administration of LP-001 with dose 6	Biological: LP-001 Dose 6 (Single); A single dose of LP-001 (Dose 6) was administered subcutaneously.
Placebo Comparator: Cohort 7: Placebo (Single); Single dose administration of placebo drug	Biological: Placebo (Single); A single dose of placebo was administered subcutaneously.
Experimental: Cohort 8: LP-001 Dose 7 (Multiple); LP-001 with dose 7 was administered 4 times in total	Biological: LP-001 Dose 7 (Multiple); LP-001 (Dose 7) was administered multiple times subcutaneously.
Experimental: Cohort 9: LP-001 Dose 8 (Multiple); LP-001 with dose 8 was administered 4 times in total	Biological: LP-001 Dose 8 (Multiple); LP-001 (Dose 8) was administered multiple times subcutaneously.
Placebo Comparator: Cohort 10: Placebo (Multiple); Placebo drug was administered 4 times in total	Biological: Placebo (Multiple); Placebo was administered multiple times subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Number of subjects with treatment-related Treatment Emergent Adverse Events (TEAEs).	Observation for 36 days after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to peak concentration (Tmax) of LP-001	The time when the blood drug concentration reaches its peak after a single dose of medication.	Observation for 36 days after administration
Maximum concentration (Cmax) of LP-001	The maximum concentration of LP-001 in the bloodstream after administration.	Observation for 36 days after administration
Elimination half-life (t1/2) of LP-001	The time required for the concentration of LP-005 in the bloodstream to decrease by half.	Observation for 36 days after administration
Area under the concentration-time curve (AUC0-t) of LP-001	The time required for the concentration of LP-005 in the bloodstream to decrease by half.	Observation for 36 days after administration
Apparent clearance rate (CL/F) of LP-001	The ratio of drug clearance to drug concentration, represents the apparent clearance of a drug after administration, adjusted for bioavailability.	Observation for 36 days after administration
Assessment of immunogenicity	The proportion of anti drug antibody (ADA) positive subjects at different detection time points.	Observation for 36 days after administration
Assessment of hemoglobin (Hb) change	Concentration of Hemoglobin changes from baseline at various time points of assessment.	Observation for 36 days after administration
Assessment of red blood cell (RBC) count change	The count of RBC changes from baseline at various time points of assessment.	Observation for 36 days after administration
Assessment of reticulocyte (Rtc) count change	The count of Rtc changes from baseline at various time points of assessment.	Observation for 36 days after administration

Collaborators and Investigators

• Sponsor: Longbio Pharma

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2022
• Primary Completion (Actual): January 2, 2024
• Study Completion (Estimated): April 6, 2024

Study Registration Dates

• First Submitted: February 20, 2024
• First Submitted That Met QC Criteria: February 27, 2024
• First Posted (Estimated): March 5, 2024

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Preleukemia
• Other Study ID Numbers: P-10-LP001-2022-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No