Clinical trial NCT05112159: Study of IPG1094 in Healthy Participants
Official title: A Phase 1, First-in-human, Randomized, Double-blind, Placebo-controlled, Single Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics (PK) of Orally Administered IPG1094 in Healthy Adult Participants
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Safety Issues
Keywords: Healthy Volunteers
Lead sponsor: Nanjing Immunophage Biotech Co., Ltd
Sponsor class: INDUSTRY
First posted: 2021-11-08
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase 1, first-in-human, randomized, double-blind, placebo-controlled, single dose escalation study to evaluate the safety, tolerability, and PK of single dose orally administered IPG1094 in healthy adult participants.


Eligibility criteria: Inclusion Criteria:

Participants must meet all of the following criteria to be included in the study:

Demography

1. Healthy adult male or female participants between 18 and 50 years of age (inclusive).
2. Body weight between 50 and 100 kg (inclusive) and body mass index (BMI) within 18\~32 kg/m2 (inclusive).

   Health status
3. In good health as determined by screening tests. Good health is defined as having no clinically relevant abnormalities identified by a detailed medical history, full physical examination (including measurement of blood pressure and pulse rate), 12-lead ECG, and clinical laboratory tests.

   Vital signs (measured after resting for 5 minutes seated position) within normal range, or outside the normal range and not considered clinically significant by the Investigator.

   Standard 12-lead ECG parameters (recorded after resting for 5 minutes in supine position) in the following ranges; corrected QT interval(QTc) (Fridericia algorithm recommended) ≤ 450 ms for males and 470 ms for females, and normal ECG tracing, or abnormal ECG tracing not considered clinically relevant by the Investigator.

   Laboratory parameters demonstrating no clinically significant abnormalities, as determined by the Investigator. A total bilirubin outside the normal range may be acceptable if total bilirubin does not exceed 1.5 × upper limit of normal(ULN) conjugated bilirubin (with the exception of a participant with documented Gilbert syndrome).
4. A negative result on urine drug screen and a repeat negative result on Day -1 (amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates).
5. Female participants must not be pregnant or breastfeeding and must use an effective contraception method (as described in Section 4.5.4), with the exception of participants who have undergone sterilization in the preceding 3 months, or who are postmenopausal.

   A woman of childbearing potential (WOCBP) must undergo pregnancy testing prior to the first dose of the Investigational Medicinal Product (IMP). The participant must be excluded from the study if the serum pregnancy test is positive.

   A postmenopausal state is defined as 12 months of amenorrhea without an alternative medical cause. In the absence of 12 months of amenorrhea, menopause may be confirmed by follicle stimulating hormone（FSH） measurement (\> 40 IU/L or milli-International unit（mIU）/mL).Females on Hormonal Replacement therapy (HRT ), where menopausal status is indeterminate, will be required to use a non-estrogen hormonal contraceptive method if participants wish to continue their HRT during the study. Participants must otherwise discontinue HRT to allow for confirmation of postmenopausal status prior to enrollment in the study.

   Regulation
6. Provide written informed consent prior to undertaking any study-related procedures.
7. Must not be under any administrative or legal supervision or under institutionalization as per a regulatory or juridical order.

Exclusion Criteria:

Participants who meet any of the following criteria will be excluded from the study:

Medical history and clinical status

1. Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, musculoskeletal, rheumatological, psychiatric, systemic, ocular, or infectious disease, or signs of acute illness.
2. Frequent severe headaches and/or migraines, recurrent nausea and/or vomiting (defined as vomiting more than twice a month).
3. Made a blood donation of any volume within 2 months prior to the first dose.
4. Symptomatic postural hypotension, irrespective of actual decrease in blood pressure, or asymptomatic postural hypotension with a decrease in systolic blood pressure ≥30 mmHg within 3 minutes of moving from supine to standing position.
5. Presence or history of drug hypersensitivity, or anaphylactic reaction, diagnosed and treated by a physician.
6. Known hypersensitivity to any component of the IMP formulation.
7. History or presence of drug or alcohol abuse (defined as alcohol consumption more than 2 units per day on a regular basis).
8. Regular smoking (defined as more than 5 cigarettes or equivalent per week), or unable to stop smoking during the study. Occasional smokers may be enrolled.
9. Excessive consumption of beverages containing xanthine bases (defined as more than 4 glasses per day).

   Interfering substances
10. Any medication, including St John's Wort, within 14 days prior to administration of the first dose or within 5 times the elimination half-life or pharmacodynamic half-life of the medication, with the exception of hormonal contraception, menopausal hormone replacement therapy, or occasional paracetamol at doses up to 2g/day.
11. Any consumption of grapefruit or products containing grapefruit within 5 days prior to the first dose administration.
12. Any vaccination in the 28 days prior to administration of the first dose.

    General conditions
13. Any participant who, in the judgment of the Investigator, is likely to be non-compliant during the study, or to be unable to cooperate due to language problems or poor mental development.
14. Any participant who enrolled in or participated in any other clinical study involving an investigational medicinal product, or in any other type of medical research within 1 month or within 5 times the elimination half-life prior to administration of the first dose.
15. Any participant who cannot be contacted in the case of an emergency.
16. Any participant who is the Investigator or any sub-investigator, research assistant, pharmacist, study coordinator, or other staff thereof directly involved in conducting the study or any person dependent on (employees or immediate family members) the study site, the Investigator or the Sponsor.

    Biological status
17. Positive result on any of the following tests: hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (HBcAb), anti-hepatitis C virus antibodies (anti-HCV), anti-human immunodeficiency virus 1 and 2 antibodies（anti-HIV1 and anti-HIV2 Ab).
18. Positive alcohol test.
19. Any participant in whom venous blood collection is difficult.

Primary outcomes:
measure: Occurrence of all adverse events
timeFrame: Up to 8 days
measure: RBC
timeFrame: Up to 8 days
measure: white blood cell count (WBC)
timeFrame: Up to 8 days
measure: platelet count (PLT)
timeFrame: Up to 8 days
measure: haemoglobin (HGB)
timeFrame: Up to 8 days
measure: mean corpuscular hemoglobin
timeFrame: Up to 8 days
measure: mean corpuscular hemoglobin concentration
timeFrame: Up to 8 days
measure: Hematocrit
timeFrame: Up to 8 days
measure: mean corpuscular volume (MCV)
timeFrame: Up to 8 days
measure: absolute differential leukocyte count (eosinophils)
timeFrame: Up to 8 days
measure: absolute differential leukocyte count (monocytes)
timeFrame: Up to 8 days
measure: absolute differential leukocyte count (lymphocytes)
timeFrame: Up to 8 days
measure: absolute differential leukocyte count (basophils)
timeFrame: Up to 8 days
measure: absolute differential leukocyte count (neutrophils)
timeFrame: Up to 8 days
measure: Temperature (°C )
timeFrame: Up to 8 days
measure: Respiration rate
timeFrame: Up to 8 days
measure: Pulse rate
timeFrame: Up to 8 days
measure: Blood pressure (both systolic and diastolic)
timeFrame: Up to 8 days
measure: Standard 12-lead ECG - heart rate
timeFrame: Up to 8 days
measure: Standard 12-lead ECG - QTcF
timeFrame: Up to 8 days
measure: Standard 12-lead ECG - PR
timeFrame: Up to 8 days
measure: Standard 12-lead ECG - QRS
timeFrame: Up to 8 days
measure: Standard 12-lead ECG - QT
timeFrame: Up to 8 days
measure: Alanine aminotransferase (ALT)
timeFrame: Up to 8 days
measure: albumin (ALB)
timeFrame: Up to 8 days
measure: alkaline phosphatase (ALP)
timeFrame: Up to 8 days
measure: aspartate aminotransferase (AST)
timeFrame: Up to 8 days
measure: total bilirubin (TBil)
timeFrame: Up to 8 days
measure: Urea
timeFrame: Up to 8 days
measure: calcium (Ca)
timeFrame: Up to 8 days
measure: chloride (Cl)
timeFrame: Up to 8 days
measure: cholesterol (CHO)
timeFrame: Up to 8 days
measure: creatinine (Cr)
timeFrame: Up to 8 days
measure: creatine kinase (CK)
timeFrame: Up to 8 days
measure: glucose (Glu)
timeFrame: Up to 8 days
measure: lactate dehydrogenase (LDH)
timeFrame: Up to 8 days
measure: phosphate (P)
timeFrame: Up to 8 days
measure: potassium (K)
timeFrame: Up to 8 days
measure: sodium (Na)
timeFrame: Up to 8 days
measure: total protein (TP)
timeFrame: Up to 8 days
measure: Prothrombin time (PT)
timeFrame: Up to 8 days
measure: activated partial thromboplastin time (APTT)
timeFrame: Up to 8 days
measure: fibrinogen
timeFrame: Up to 8 days
measure: international normalized ratio (INR)
timeFrame: Up to 8 days
measure: pH
timeFrame: Up to 8 days
measure: Bilirubin (U-BIL)
timeFrame: Up to 8 days
measure: glucose (GLU)
timeFrame: Up to 8 days
measure: urine erythrocytes (U-RBC)
timeFrame: Up to 8 days
measure: ketones (U-KET)
timeFrame: Up to 8 days
measure: Urinary leukocyte (U-LEU)
timeFrame: Up to 8 days
measure: nitrites (U-NIT)
timeFrame: Up to 8 days
measure: protein (U-PRO)
timeFrame: Up to 8 days
measure: specific gravity (U-SG)
timeFrame: Up to 8 days
measure: urobilinogen (URO)
timeFrame: Up to 8 days
Secondary outcomes:
measure: Maximum plasma concentration（Cmax）
timeFrame: Blood samples will be collected at 0 h before administration (within 1h prior to administration), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 24, 36, 48, 72, and 96 h after administration.
measure: Time to Cmax (tmax)
timeFrame: Blood samples will be collected at 0 h before administration (within 1h prior to administration), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 24, 36, 48, 72, and 96 h after administration.
measure: Area under the serum concentration-time curve (AUC[0-t]
timeFrame: Blood samples will be collected at 0 h before administration (within 1h prior to administration), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 24, 36, 48, 72, and 96 h after administration.
measure: Area under the serum concentration-infinity curve AUC[0-infinity]
timeFrame: Blood samples will be collected at 0 h before administration (within 1h prior to administration), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 24, 36, 48, 72, and 96 h after administration.
measure: Apparent terminal phase half-life (t1/2)
timeFrame: Blood samples will be collected at 0 h before administration (within 1h prior to administration), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 24, 36, 48, 72, and 96 h after administration.
Other outcomes:
Locations:
city: Randwick
country: Australia
facility: Scientia Clinical Research Ltd
state: New South Wales
Study officials:
affiliation: Nanjing Immunophage Biotech Co., Ltd
name: Wang Jianfei
role: STUDY_DIRECTOR
References: