Clinical trial NCT05679258: A Study to Compare the PK , Safety, Tolerability, and Immunogenicity of HLX15 With Daratumumab in Male Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: pharmacokinetics
CD38
multiple myeloma
Lead sponsor: Shanghai Henlius Biotech
Sponsor class: INDUSTRY
First posted: 2023-01-10
Enrollment: 172
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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

Eligibility criteria: 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.

Primary outcomes:
measure: Area under the serum concentration-time curve from time 0 to infinity (AUC0-inf).
timeFrame: Up to Day 91
Secondary outcomes:
measure: Area under the serum concentration-time curve from time 0 to the last measurable concentration (AUC0-t);
timeFrame: Up to Day 91
measure: Maximum (peak) serum drug concentration (Cmax);
timeFrame: Up to Day 91
measure: Time to reach maximum (peak) serum drug concentration (Tmax);
timeFrame: Up to Day 91
measure: Volume of distribution during the terminal phase (Vz);
timeFrame: Up to Day 91
measure: Elimination half-life (t1/2);
timeFrame: Up to Day 91
measure: Total clearance (CL);
timeFrame: Up to Day 91
measure: Percentage of area under serum concentration-time curve obtained by extrapolation (%AUCex).
timeFrame: Up to Day 91
Other outcomes:
measure: Adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs);
timeFrame: Up to Day 91
measure: Number of participants with abnormal vital signs
timeFrame: Up to Day 91
measure: Number of participants with abnormal physical examination findings;
timeFrame: Up to Day 91
measure: Number of participants with abnormal Laboratory tests results (hematology, serum chemistry, and urinalysis);
timeFrame: Up to Day 91
measure: Number of participants with abnormal 12-lead ECG readings.
timeFrame: Up to Day 91
measure: Incidence rate of anti-drug antibody (ADA) and NAb
timeFrame: Up to Day 91
Locations:
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Nanjing
country: China
facility: Sir Run Run Hospital, Nanjing Medical University
state: Jiangsu
Study officials:
References: