A Study to Compare the PK , Safety, Tolerability, and Immunogenicity of HLX15 With Daratumumab in Male Subjects

A Phase I Study to Compare the Pharmacokinetic Characteristics, Safety, Tolerability, and Immunogenicity (Randomized, Double-blind, Parallel Controlled) of HLX15 With Daratumumab Injection in Healthy Chinese Male Subjects

Phase I Study to Compare the Pharmacokinetic Characteristics, Safety, Tolerability, and Immunogenicity (Randomized, Double-blind, Parallel Controlled) of HLX15 with Daratumumab Injection in Healthy Chinese Male Subjects

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: HLX15; Drug: US-sourced DARZALEX®; Drug: CN-sourced DARZALEX®; Drug: EU-sourced DARZALEX®

Detailed Description

This study contains two parts. Part I of the study is a single-center, randomized, open-label, 2-arm, parallel-controlled phase Ia study to compare the PK characteristics, safety, tolerability, and immunogenicity of HLX15 and daratumumab infusion (DARZALEX®, CN-sourced) in healthy Chinese male subjects.

A total of 24 healthy Chinese male subjects will be enrolled in this part and randomized to the HLX15 group or the CN-sourced DARZALEX® group in a 1:1 ratio, with 12 subjects in each group. The subjects will receive a single dose (8 mg/kg) of HLX15 or CN-sourced DARZALEX® via intravenous infusion.

There is a safety run-in period in the early stage of the study to investigate the safety and tolerability of HLX15 in healthy Chinese male subjects. Another 3-6 subjects will be enrolled to receive the investigational product HLX15 and safety observation will be conducted for 1 week. The Safety Review Committee (SRC) will decide whether to adjust the subsequent study plan based on the safety and tolerability data after administration.

Part II of the study is a multicenter, randomized, double-blind, 3-arm, parallel-controlled phase Ib study to compare similarity of the PK characteristics, safety, tolerability, and immunogenicity of HLX15 and daratumumab infusion (DARZALEX®, US-sourced; DARZALEX®, CN-sourced) in healthy Chinese male subjects.A total of 204 healthy Chinese male subjects are planned to be enrolled in this part and randomly assigned in a 1:1:1 ratio to the HLX15 group, the US-sourced DARZALEX® group, or the CN-sourced DARZALEX® group, with 68 subjects in each group. The subjects will receive a single dose (8 mg/kg) of HLX15, US-sourced DARZALEX®, or CN-sourced DARZALEX® via intravenous infusion.This part may be adjusted according to the results of Part I, including sample size and sampling time points

• Study Type: Interventional
• Enrollment (Estimated): 172
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Beijing Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 211112
      • Sir Run Run Hospital, Nanjing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age ≥ 18 years and ≤ 60 years at the time of signing the informed consent form (ICF);
2. Sex: male;
3. Body weight and body mass index (BMI): 18.5 kg/m2 ≤ BMI < 28 kg/m2; body weight ≥ 55 kg;
4. The subject should be judged by the physician to be in good general health according to the results of medical history, physical examination, vital signs, ECG examination, laboratory tests, etc. (normal or abnormal without clinical significance);
5. The subject should be a voluntary participant who has understood and signed the ICF.

Exclusion Criteria:

1. Subjects who may have diseases that affect their safety or affect the study results, including but not limited to cardiovascular, respiratory, endocrine, metabolic, renal, hepatic, gastrointestinal tract, skin, infection, malignant tumor, hematologic, skeletal, genitourinary, nervous system/ psychiatric or functional disorders, which are judged as clinically significant by the investigator;
2. With acute, chronic, or latent infectious diseases within 1 month before administration;
3. With known immune system diseases (autoimmune diseases and immunodeficiency diseases), including but not limited to autoimmune hemolytic anemia;
4. Has experienced a recent single dermatomal herpes zoster eruption within 6 months before administration;
5. Has a history of multi-dermatomal herpes zoster or central nervous system (CNS) herpes zoster during the screening period or before;
6. Positive for indirect antiglobulin test (Indirect Coombs test);
7. Use of monoclonal antibody, cell therapy, etc. within 6 months before administration, or daratumumab or its analogues or drugs targeting CD38 before administration;
8. Use of any medication, including prescription drugs, over-the-counter (OTC) drugs, and Chinese herbal medicines, within 2 weeks before administration;
9. History of drug or food allergy, including allergy to any drug or drug excipient used in the study;
10. Fear of needles or blood, or difficulty in venous blood collection (history of difficult blood collection or corresponding symptoms and signs, unable to tolerate venipuncture);
11. History of blood donation or total blood loss of 200 mL or more within 3 months before administration;
12. Participants in clinical trials of any other drug or device within 3 months (or 5 half-lives of the corresponding investigational product if the half-life of the drug is long (5 half-lives > 3 months)) before administration;
13. Major surgery within 3 months before signing the ICF;
14. Positive for hepatitis B virus (HBsAg or HBcAb-positive) antibodies, hepatitis C virus (HCV) antibodies, human immunodeficiency virus (HIV), or treponema pallidum antibodies (Anti-TP);
15. History of drug abuse or substance abuse, or positive in urine drug screening;
16. Patients who have been vaccinated with attenuated or live virus vaccine (such as Bacille Calmette-Guérin, BCG) or viral vector vaccine within 12 months before the first dose, or who plan to be vaccinated with such vaccines within 12 months after administration;
17. Patients who have been vaccinated with vaccines other than the above attenuated or live viral vaccines and viral vector vaccines within 1 month before the first dose, such as inactivated vaccines and recombinant subunit vaccines;
18. Male subjects with partners of childbearing potential who have a plan to father a child and/or donate sperm from signing of ICF through 3 months after administration, do not agree to abstain completely from sexual intercourse, or plan to use a contraceptive method that is not acceptable to the investigator (unacceptable methods of contraception include: i. periodic abstinence <such as calendar method, ovulation method, basal body temperature method, post-ovulation safety period method, etc.>, withdrawal, etc.; ii. medical contraceptive measures such as oral contraceptives, contraceptive injections, contraceptive patches, subcutaneous implantation, intrauterine hormone contraceptive devices, local contraceptives such as spermicides, etc.);
19. Subjects with any other conditions that, in the judgment of the investigator, are ineligible for participation in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HLX15 group; Recombinant anti-CD38 fully human monoclonal antibody injection developed by Shanghai Henlius Biotech, Inc.	Drug: HLX15; A single dose (8 mg/kg) of HLX15 via intravenous infusion.; Other Names: Recombinant anti-CD38 fully humanized monoclonal antibody injection
Active Comparator: US-sourced DARZALEX® group; Daratumumab injection	Drug: US-sourced DARZALEX®; A single dose (8 mg/kg) of US-sourced DARZALEX® via intravenous infusion.; Other Names: Daratumumab Injection
Active Comparator: CN-sourced DARZALEX® group; Daratumumab injection	Drug: CN-sourced DARZALEX®; A single dose (8 mg/kg) of CN-sourced DARZALEX® via intravenous infusion.; Other Names: Daratumumab Injection
Active Comparator: EU-sourced DARZALEX® group; Daratumumab injection	Drug: EU-sourced DARZALEX®; A single dose (8 mg/kg) of EU-sourced DARZALEX® via intravenous infusion.; Other Names: Daratumumab Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the serum concentration-time curve from time 0 to infinity (AUC0-inf).	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 91

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the serum concentration-time curve from time 0 to the last measurable concentration (AUC0-t);	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 91
Maximum (peak) serum drug concentration (Cmax);	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 91
Time to reach maximum (peak) serum drug concentration (Tmax);	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 91
Volume of distribution during the terminal phase (Vz);	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 91
Elimination half-life (t1/2);	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 91
Total clearance (CL);	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 91
Percentage of area under serum concentration-time curve obtained by extrapolation (%AUCex).	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 91

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs);	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 91
Number of participants with abnormal vital signs	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 91
Number of participants with abnormal physical examination findings;	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 91
Number of participants with abnormal Laboratory tests results (hematology, serum chemistry, and urinalysis);	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 91
Number of participants with abnormal 12-lead ECG readings.	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 91
Incidence rate of anti-drug antibody (ADA) and NAb	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 91

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2023
• Primary Completion (Actual): March 16, 2024
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: December 21, 2022
• First Submitted That Met QC Criteria: January 9, 2023
• First Posted (Actual): January 10, 2023

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: pharmacokinetics; multiple myeloma; CD38
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Multiple Myeloma; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Daratumumab; Antibodies, Monoclonal
• Other Study ID Numbers: HLX15-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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