A phase 1 first-in-human, randomized, double–blind, placebo-controlled doseescalation trial of a single intravenous dose of the anti-herpes simplex virusmonoclonal antibody HDIT101 in healthy volunteers
- Conditions
- A60Anogenital herpesviral [herpes simplex] infection
- Registration Number
- DRKS00014678
- Lead Sponsor
- Heidelberg ImmunoTherapeutics GmbH c/o NCT
- Brief Summary
HDIT101 is a first-in-class humanized monoclonal antibody recognizing a conserved epitope in glycoprotein B, a target present on the surface of herpes simplex virus 1 (HSV-1) and HSV-2 particles as well as on virus-infected cells. This was a first-in-human, single-center, double-blind, placebo-controlled trial in 24 healthy volunteers, randomized 3:1 (placebo:active) in each of the six dose levels with escalating doses up to 12,150 mg HDIT101. HDIT101 was administered intravenously, to study safety, pharmacokinetics (PKs), and immunogenicity. HDIT101 was well-tolerated in all recipients and no serious or severe adverse events, no infusion-related reactions, and no events suggestive of dose limiting off-target toxicity occurred. The mean serum exposure (area under the curve from zero to infinity [AUC0-8 ]) of HDIT101 showed a linear increase from 4340 h*µg/ml at a dose of 50 mg to 1,122,247 h*µg/ml at a dose of 12,150 mg. No immunogenic effects following HDIT101 exposure were observed at any of the applied doses. HDIT101 demonstrated the expected PK properties of a monoclonal antibody was well-tolerated, and could be safely administered even at excessively high doses that may be required for treatment of patients with septical HSV spread.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 24
Check at screening and at Day 1 (up to 72 h before dosing)
(1) Ability to provide written, personally signed and dated informed consent to participate in the trial.
(2) Understanding, ability, and willingness to fully comply with trial interventions and restrictions.
(3) Healthy male or female volunteer = 18 years and = 60 years at the time of informed consent.
(4) Adequate access to the peripheral venous system allowing the insertion of two peripheral venous cannulas (1x left arm, 1x right arm) and repetitive sampling of blood samples.
(5) Body mass index of = 18 and = 30 kg/m².
(6) Satisfactory medical assessment with no clinically significant or relevant abnormalities as determined by medical history, physical examination, vital signs, electrocardiogram (ECG), and laboratory evaluation (hematology, biochemistry, coagulation, and urinalysis) as assessed by a physician who is a member of the trial team.
(7) Adequate liver, renal, and bone marrow function as defined by a. ASAT and ALAT = 1.3 upper limit of the normal (ULN). b. Alkaline phosphatase and gGT = 1.5 ULN. c. Total bilirubin = 1.3 ULN, except in case of suspected Gilbert’s disease: non-fasting total bilirubin = 1.3 ULN and fasting total bilirubin = 2.0 ULN is acceptable. d. Estimated glomerular filtration rate (eGFR) calculated with the Cockcroft & Gault formula = 60 mL/min. e. Hemoglobin = 12.0 g/dL for male participants and = 11.0 g/dL for female participants. f. Platelets = 140 / nL. g. White blood cell count (WBC) = 3.5 / nL (participants with a
WBC = 3.0 / nL and < 3.5 / nL may be included after consultation with a hematologist).
(8) Adequate cardiovascular function defined by a. Resting systolic blood pressure = 100 mmHg and < 140 mmHg. b. Resting diastolic blood pressure = 50 mmHg and < 90 mmHg. c. Resting heart rate = 50 beats per minute (bpm) and = 100 bpm. d. No clinically relevant findings in the ECG.
(9) Women of childbearing potential1 (WCBP) must have a negative ß-HCG urine or blood test within 72 h before receiving treatment.
(10) WCBP and men with partners of childbearing potential are only included if they confirm to remain sexually inactive, have a sterilized partner, or to use reliable contraception with a Pearl Index < 1 % (i.e. two independent effective contraceptive methods: combined hormonal contraception associated with inhibition of ovulation [oral, intravaginal, or transdermal], progestogen-only hormonal contraception associated with inhibition of ovulation [oral, injectable, or implantable], intrauterine device, or intrauterine hormone-releasing system) during the trial and for 12 weeks after the administration of trial medication.
Check at screening and at Day 1 (up to 72 h before dosing)
(1) Active HSV infection (i.e. visible HSV lesion on skin or mucosa)
(2) Current or relevant history of physical or psychiatric illness with a risk of relapse as judged by the investigator, any medical disorder that may require treatment or make the participant unlikely to fully complete the trial, or any condition that presents undue risk from the HDIT101 administration or trial interventions.
(3) Any condition that precludes the sampling of max. 350 mL of blood over the duration of the trial.
(4) Participants must refrain from blood / plasma donation up to 12 weeks after dosing of HDIT101.
(5) Use of any prescription medication (except contraceptive pills, iodine, or thyroid hormones) within 14 d prior to administration of the IMP.
(6) Male participants who consume more than 21 units (1 unit = 8 g alcohol) of alcohol per week or 3 units per day. Female participants who consume more than 14 units of alcohol per week or 2 units per day.
(7) A positive result in drug OR alcohol test at screening.
(8) A positive HIV antibody screen, hepatitis B virus (HBV) infection screen, OR hepatitis C virus (HCV) antibody screen.
(9) Any known allergies to drugs or any history of severe allergic or anaphylactic reactions OR any other clinically significant allergies (mild forms of hay fever are acceptable, if currently asymptomatic without treatment).
(10) Active enrollment in another clinical drug trial or last administration of study drug in a clinical drug trial within the last 30 d or within 5 half-lives of the previous drug(s), whichever is longer.
(11) Prior vaccination with a HSV type 1/2 vaccine (e.g. experimental).
(12) Pregnant or breast-feeding women.
(13) Any other medical condition that would, in the opinion of the Investigator, limit participant ability to complete the trial.
(14) Known intolerance to the active substance or excipients of the IMP.
(15) Previous participation in this trial unless screening failure
Additional check at Day 1
(16) A positive result in drug OR alcohol test at Day 1.
(17) History of vaccination within 30 d prior to dosing of the IMP.
(18) Use of any non-prescription medication or over-the-counter (OTC) medicine (including herbal preparations) with pharmacologically active ingredients within 14 d prior to the dosing of HDIT101.
(19) Consumption of any alcohol-containing products within 24 h prior to Day 1 and throughout the duration of the participant's stay in the Clinical Research Unit.
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary endpoint of the trial is the number of participants experiencing a DLT (dose-limiting toxicity) during the 48-h observation period up to Visit 3 on<br>Day 3
- Secondary Outcome Measures
Name Time Method The incidence rate, severity, and relatedness to HDIT101 of AEs, and serious adverse drug events (SAE). AEs may be identified by physical examination, laboratory parameters, vital signs, or ECG.<br>- Non-compartmental PK characteristics of HDIT101 and population pharmacokinetic modeling of PK data if deemed necessary<br>- Anti-drug antibodies (ADA) in blood.<br><br>48h post dose (cut-off DLT period)