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Evaluate Safety and Pharmacokinetics of HLX70 in Healthy Adult Volunteers

2022년 6월 20일 업데이트: Shanghai Henlius Biotech

A Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Phase I Clinical Study to Evaluate Safety and Pharmacokinetics of HLX70 in Healthy Adult Volunteers

A single-center, randomized, double-blind, placebo-controlled, dose escalation, phase I clinical study to evaluate safety and pharmacokinetics of HLX70 in healthy adult volunteers

연구 개요

상세 설명

A randomized, double-blind, single-dose by intravenous administration, placebo-controlled, dose escalation, first-in-human study is proposed to evaluate the safety, PK, and immunogenicity of HLX70 in healthy subjects. We plan to enroll 8 subjects in each of the 3 dose cohorts at 3 mg/kg, 10 mg/kg, and 30 mg/kg, of which 2 receive intravenous injections of placebo and 6 receive intravenous injections of the investigational product (IP). A total of 24 subjects will be enrolled.

연구 유형

중재적

단계

  • 1단계

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 (성인)

건강한 자원 봉사자를 받아들입니다

연구 대상 성별

모두

설명

Inclusion Criteria:

  1. Subjects with voluntary signing of the informed consent form (ICF);
  2. Healthy males or females aged ≥ 18 and ≤ 60 years at the time of signing the ICF;
  3. Subjects with body weight ≥ 50 kg and body mass index (BMI) must be higher than 18.5 kg/m2 and lower than 30 kg/m2 at screening visit ;
  4. Subjects who are determined to be in good health according to medical history, normal (site normal ranges to be followed) or abnormal but clinically insignificant physical examination, vital signs, ECG, laboratory test results (including hematology, serum chemistry, coagulation function, urinalysis, etc.), and investigator's clinical judgment (CTCAE grade 1 of triglycerides and uric acid is permitted). One re-test allowed per investigator discretion to confim result.
  5. Subject who agrees that he and his spouse or partner will use reliable contraception for 9 months after administration.

Exclusion Criteria:

  1. Subjects with the lab-confirmed medical history of COVID-19, including nucleic acid (PCR testing of nasopharyngeal samples) tested positive or antibody IgG/IgM tested positive.
  2. Subjects with the novel onset of pyrexia/cough/shortness of breath/diarrhea or history of contact with confirmed COVID-19 individuals (positive for SARS-CoV-2 nucleic acid) within the 14 days before randomization.
  3. Subjects who are known to have chronic obstructive pulmonary disease (COPD), cirrhosis of liver, cardiac failure or any condition that requires active medical intervention or monitoring to avert serious danger to the participant's health or well-being.
  4. Subjects with pneumonia or tuberculosis (TB) suggested by chest X-Ray.
  5. Subjects with previous exposure to a mAb or any other biological agents in 6 months before screening.
  6. Subjects with previous exposure to vaccines in 3 months before screening, or who plans to receive vaccination during the study period or in 3 months after the study.
  7. Subjects with previous participation in clinical trials receiving investigational drug/comparator within the longer of 30 days or 5 half-lives before screening.
  8. Subjects who are known to have a history of allergy to any mAb, biological product, protein product, or the ingredient of the IP.
  9. Subjects with positive test result(s) for hepatitis B virus (positive for HBsAg or positive for HBcAb and HBV-DNA), hepatitis C virus (HCV) antibodies, human immunodeficiency virus (HIV) antibodies, or treponema pallidum.
  10. Subjects who are known to have a history of psychotropic drug abuse, alcoholism, or drug addiction within the last year.
  11. Subjects with a history of a blood donation within 3 months before screening.
  12. Subjects with the use of any prescription drug, OTC drug, or traditional Chinese medicine in 14 days before screening.
  13. Females who are pregnant or breastfeeding
  14. Other factors that the Investigator deems inappropriate for participation in the study.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 다른
  • 할당: 무작위
  • 중재 모델: 순차적 할당
  • 마스킹: 네 배로

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: HLX70 3 mg/kg or Placebo
Random allocation to HLX70 3 mg/kg (IV, single dose), or placebo (IV, single dose) of which 2 receive intravenous injections of placebo and 6 receive intravenous injections of the HLX70.
단일 용량, 정맥 주입
다른 이름들:
  • 주입을 위한 재조합형 인간화된 반대로 S 단백질 단클론 항체
Single-dose, intravenous infusion
실험적: HLX70 10 mg/kg or Placebo
Random allocation to HLX70 10 mg/kg (IV, single dose), or placebo (IV, single dose) of which 2 receive intravenous injections of placebo and 6 receive intravenous injections of the HLX70.
단일 용량, 정맥 주입
다른 이름들:
  • 주입을 위한 재조합형 인간화된 반대로 S 단백질 단클론 항체
Single-dose, intravenous infusion
실험적: HLX70 30 mg/kg or Placebo
Random allocation to HLX70 30 mg/kg (IV, single dose), or placebo (IV, single dose) of which 2 receive intravenous injections of placebo and 6 receive intravenous injections of the HLX70.
단일 용량, 정맥 주입
다른 이름들:
  • 주입을 위한 재조합형 인간화된 반대로 S 단백질 단클론 항체
Single-dose, intravenous infusion

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Number of participants with adverse events, serious adverse event and infusion-related reactions as assessed by CTCAE v5.0
기간: up to 92 days.
Safety follow-up: All subjects in the study will undergo safety follow-up within 92 days after administration and receive routine laboratory tests on day 2, day 3, day 8, day 15, day 22 and day 29 post administration (see the study procedures for details). A telephone follow-up will be followed every week until day 92 (day 1 is defined as the day of IP infusion). For a subject suffering AE during the observation period, follow-up shall be continued until the AE returns to the baseline or it is stable from getting worse.
up to 92 days.
Safety evaluation- proportion of subjects undergoing DLT events
기간: Days 1 to 7.
The proportion of subjects undergoing DLT events
Days 1 to 7.

2차 결과 측정

결과 측정
측정값 설명
기간
PK parameters-Areas under the concentration-time curves
기간: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK blood sampling points: All subjects in the study will participate in the PK study. PK blood sampling timepoints: pre-infusion, immediately post-infusion, and 3 h, 6 h, 10 h, 24 h(Day 2), 48 h (day 3) , 96 h (day 5), 168 h (day 8) , 240h (day 11) , 336 h (day 15), 504 h (day 22) , 672 (day 29) , 1008 h (day 43) ,1344 h (day 57), 1680 h (day 71) , and 2184 h (day 92), after HLX70 infusion. There are a total of 17 blood sampling time points.
pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK parameters-Maximum measured concentration
기간: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK blood sampling points: All subjects in the study will participate in the PK study. PK blood sampling timepoints: pre-infusion, immediately post-infusion, and 3 h, 6 h, 10 h, 24 h(Day 2), 48 h (day 3) , 96 h (day 5), 168 h (day 8) , 240h (day 11) , 336 h (day 15), 504 h (day 22) , 672 (day 29) , 1008 h (day 43) ,1344 h (day 57), 1680 h (day 71) , and 2184 h (day 92), after HLX70 infusion. There are a total of 17 blood sampling time points.
pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK parameters-Time from dosing to maximum measured concentration
기간: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK blood sampling points: All subjects in the study will participate in the PK study. PK blood sampling timepoints: pre-infusion, immediately post-infusion, and 3 h, 6 h, 10 h, 24 h(Day 2), 48 h (day 3) , 96 h (day 5), 168 h (day 8) , 240h (day 11) , 336 h (day 15), 504 h (day 22) , 672 (day 29) , 1008 h (day 43) ,1344 h (day 57), 1680 h (day 71) , and 2184 h (day 92), after HLX70 infusion. There are a total of 17 blood sampling time points.
pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK parameters-Terminal phase elimination rate constant
기간: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK blood sampling points: All subjects in the study will participate in the PK study. PK blood sampling timepoints: pre-infusion, immediately post-infusion, and 3 h, 6 h, 10 h, 24 h(Day 2), 48 h (day 3) , 96 h (day 5), 168 h (day 8) , 240h (day 11) , 336 h (day 15), 504 h (day 22) , 672 (day 29) , 1008 h (day 43) ,1344 h (day 57), 1680 h (day 71) , and 2184 h (day 92), after HLX70 infusion. There are a total of 17 blood sampling time points.
pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK parameters-Terminal phase elimination half life
기간: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK blood sampling points: All subjects in the study will participate in the PK study. PK blood sampling timepoints: pre-infusion, immediately post-infusion, and 3 h, 6 h, 10 h, 24 h(Day 2), 48 h (day 3) , 96 h (day 5), 168 h (day 8) , 240h (day 11) , 336 h (day 15), 504 h (day 22) , 672 (day 29) , 1008 h (day 43) ,1344 h (day 57), 1680 h (day 71) , and 2184 h (day 92), after HLX70 infusion. There are a total of 17 blood sampling time points.
pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK parameters-Clearance
기간: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK blood sampling points: All subjects in the study will participate in the PK study. PK blood sampling timepoints: pre-infusion, immediately post-infusion, and 3 h, 6 h, 10 h, 24 h(Day 2), 48 h (day 3) , 96 h (day 5), 168 h (day 8) , 240h (day 11) , 336 h (day 15), 504 h (day 22) , 672 (day 29) , 1008 h (day 43) ,1344 h (day 57), 1680 h (day 71) , and 2184 h (day 92), after HLX70 infusion. There are a total of 17 blood sampling time points.
pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK parameters-Volume of distribution during terminal phase and at steady state
기간: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK blood sampling points: All subjects in the study will participate in the PK study. PK blood sampling timepoints: pre-infusion, immediately post-infusion, and 3 h, 6 h, 10 h, 24 h(Day 2), 48 h (day 3) , 96 h (day 5), 168 h (day 8) , 240h (day 11) , 336 h (day 15), 504 h (day 22) , 672 (day 29) , 1008 h (day 43) ,1344 h (day 57), 1680 h (day 71) , and 2184 h (day 92), after HLX70 infusion. There are a total of 17 blood sampling time points.
pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK parameters-Mean residence time
기간: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
PK blood sampling points: All subjects in the study will participate in the PK study. PK blood sampling timepoints: pre-infusion, immediately post-infusion, and 3 h, 6 h, 10 h, 24 h(Day 2), 48 h (day 3) , 96 h (day 5), 168 h (day 8) , 240h (day 11) , 336 h (day 15), 504 h (day 22) , 672 (day 29) , 1008 h (day 43) ,1344 h (day 57), 1680 h (day 71) , and 2184 h (day 92), after HLX70 infusion. There are a total of 17 blood sampling time points.
pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.
Anti-drug antibody
기간: pre-infusion and Days 15, 29, 57 and 92.
Blood sampling time points for immunogenicity: Blood samples for anti-drug antibody (ADA) testing will be collected at pre-infusion and on day 15, day 29, day 57, and day 92 after administration; positive ADA samples will be tested for neutralizing antibody (NAb).
pre-infusion and Days 15, 29, 57 and 92.

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연구 기록 날짜

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연구 주요 날짜

연구 시작 (예상)

2020년 12월 9일

기본 완료 (예상)

2021년 9월 6일

연구 완료 (예상)

2021년 9월 18일

연구 등록 날짜

최초 제출

2022년 4월 29일

QC 기준을 충족하는 최초 제출

2022년 6월 20일

처음 게시됨 (실제)

2022년 6월 23일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2022년 6월 23일

QC 기준을 충족하는 마지막 업데이트 제출

2022년 6월 20일

마지막으로 확인됨

2022년 6월 1일

추가 정보

이 연구와 관련된 용어

기타 연구 ID 번호

  • HLX70-001US
  • 255086 (기타 식별자: CRO study number)

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

아니요

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아니

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