Study to Evaluate IMG-004 in Healthy Participants
Study Details
Study Description
Brief Summary
This first in human (FIH) study will Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Dose(s) of Orally Administered IMG-004 in Healthy Participants.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
The study is a Phase 1, randomized, double-blind, placebo-controlled study of orally administered IMG-004 to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending doses in healthy participants. The study is designed into 2 parts: single (Part A) and multiple (Part B) dose escalation study in healthy participants. Six dosing cohort levels are planned to be evaluated in Part A. Food-effect is planned to be evaluated in one of the dose cohorts. Three dosing cohorts are planned to be evaluated in Part B.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SAD cohort 1 Each participant who meets confirmation of eligibility and completion of the screening phase will be randomized to receive either a single dose of 30mg IMG-004 oral capsule(s) or a single dose of matching placebo. Participants will be admitted to the clinic on Day -1 ,remain domiciled until Day 8 and complete the safety follow-up on Day15. |
Drug: IMG-004 or placebo
Each participant will be randomized to receive either a single dose of 30mg IMG-004 oral capsule(s) or a single dose of matching placebo.
|
| Experimental: SAD cohort 2 Each participant who meets confirmation of eligibility and completion of the screening phase will be randomized to receive either a single dose of IMG-004 oral capsule(s) or a single dose of matching placebo.Participants will be admitted to the clinic on Day -1 ,remain domiciled until Day 8 and complete the safety follow-up on Day15. |
Drug: IMG-004 or placebo
Each participant will be randomized to receive either a single dose of IMG-004 oral capsule(s) or a single dose of matching placebo.
|
| Experimental: SAD cohort 3(FE cohort) Participants in the food-effect cohort will be admitted to the clinic on the first Baseline (Day -1) and remain domiciled until Day 8 in the fasted condition period. After completing the safety follow-up in fasted period, and after safety information for at least 24 hours in the sentinel participants at a higher dose level has been reviewed by the PI/designee, the same participants will be readmitted to the clinic on the second Baseline (fed period). Participants will take IMG-004 under the fed condition and domiciled 7 days after administration. The schedule of events will follow the same procedure in the fasted condition period. |
Drug: IMG-004 or placebo
Each participant will be randomized to receive either a single dose of IMG-004 oral capsule(s) or a single dose of matching placebo in the fasted and fed condition.
|
| Experimental: SAD cohort 4 Each participant who meets confirmation of eligibility and completion of the screening phase will be randomized to receive either a single dose of IMG-004 oral capsule(s) or a single dose of matching placebo.Participants will be admitted to the clinic on Day -1 ,remain domiciled until Day 8 and complete the safety follow-up on Day15. |
Drug: IMG-004 or placebo
Each participant will be randomized to receive either a single dose of IMG-004 oral capsule(s) or a single dose of matching placebo.
|
| Experimental: SAD cohort 5 Each participant who meets confirmation of eligibility and completion of the screening phase will be randomized to receive either a single dose of IMG-004 oral capsule(s) or a single dose of matching placebo.Participants will be admitted to the clinic on Day -1 ,remain domiciled until Day 8 and complete the safety follow-up on Day15. |
Drug: IMG-004 or placebo
Each participant will be randomized to receive either a single dose of IMG-004 oral capsule(s) or a single dose of matching placebo.
|
| Experimental: SAD cohort 6 Each participant who meets confirmation of eligibility and completion of the screening phase will be randomized to receive either a single dose of IMG-004 oral capsule(s) or a single dose of matching placebo.Participants will be admitted to the clinic on Day -1 ,remain domiciled until Day 8 and complete the safety follow-up on Day15. |
Drug: IMG-004 or placebo
Each participant will be randomized to receive either a single dose of IMG-004 oral capsule(s) or a single dose of matching placebo.
|
| Experimental: MAD cohort 1 Each participant who meets confirmation of eligibility and completion of a screening phase will be randomized to receive active or placebo drug orally for 8 days. Participants will be admitted on Day -1 ,domiciled until Day 13 and complete the safety follow-up on Day22. |
Drug: IMG-004 or placebo
Each participant will be randomized to active or placebo drug orally for 8 days.
|
| Experimental: MAD cohort 2 Each participant who meets confirmation of eligibility and completion of a screening phase will be randomized to receive active or placebo drug orally for 8 days. Participants will be admitted on Day -1 ,domiciled until Day 13 and complete the safety follow-up on Day22. |
Drug: IMG-004 or placebo
Each participant will be randomized to active or placebo drug orally for 8 days.
|
| Experimental: MAD cohort 3 Each participant who meets confirmation of eligibility and completion of a screening phase will be randomized to receive active or placebo drug orally for 8 days. Participants will be admitted on Day -1 ,domiciled until Day 13 and complete the safety follow-up on Day22. |
Drug: IMG-004 or placebo
Each participant will be randomized to active or placebo drug orally for 8 days.
|
Outcome Measures
Primary Outcome Measures
- The Adverse events of IMG-004 [SAD cohort from signing ICF up to to Day 15, MAD cohort from signing ICF up to to Day 22]
Adverse events, including type, incidence, grade (determined with reference to IMG-004)
Secondary Outcome Measures
- PK parameters [SAD cohort from day 1 to day 8 , MAD cohort from day 1 to day 13.]
Time for Cmax (Tmax)
Eligibility Criteria
Criteria
Inclusion Criteria:
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Healthy adult males and/or females, 18 to 60 years of age (inclusive) at the date of signed consent form.
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Body mass index (BMI) greater than or equal to 18.5 and less than 32 (kg/m2) and a minimum body weight of 45 kg.
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Able to participate and comply with all study procedures and restrictions, and willing to provide written informed consent to participate in the study.
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Male participants must agree to practice true abstinence; be surgically sterilized (performed at least 6 months prior and documented to no longer produce sperm - verbal confirmation through medical history review acceptable); or agree to use a condom plus ensure use of effective contraception by their female partner of childbearing potential (ie, established use of hormonal contraception - started at least 30 days before Day 1; or placement or an intrauterine device or intrauterine system, diaphragm with spermicide or cervical sponge with spermicide) from screening and for at least 30 days after dosing and refrain from donating sperm during this period. Contraception requirements do not apply for participants in an exclusively same-sex relationship or if their female partner is of non-childbearing potential. Males with pregnant partners may participate if they agree to use a barrier method of contraception.
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Female participants of non-childbearing potential, defined as surgically sterile (hysterectomy, bilateral salpingectomy, bilateral tubal ligation or bilateral oophorectomy, verbal confirmation through medical Confidential Page 17 of 75 history review acceptable) or postmenopausal (no menses for 12 months and confirmed by follicle-stimulating hormone (FSH) level ≥ 40 mIU/mL).
Exclusion Criteria:
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History of disease of the central nervous system, cardiovascular system, kidney, liver, digestive system, respiratory system, or metabolic/endocrine system, or other disease that in the opinion of the Investigator (or medically qualified designee) may make participation unsafe for the participant or interfere with trial evaluations or otherwise considered clinically significant.
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History of immunological abnormality (eg, primary or secondary immune suppression) that in the opinion of the Investigator (or medically qualified designee) may make participation unsafe for the participant or interfere with trial evaluations or otherwise considered clinically significant.
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History of severe immediate hypersensitivity reaction to BTK inhibitors, defined as non-cutaneous hypersensitivity reaction, requiring parenteral (IM/IV) therapy.
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Major surgery ≤ 4 weeks before Baseline visit. Participants must have also fully recovered from any surgery (major or minor) and/or its complications before initiating study treatment.
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History of malignancy or known current malignancy, except for adequately treated basal cell or squamous cell carcinoma of the skin.
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Participants who, in the Investigator's judgement, are perceived as having an increased risk of bleeding, eg, history of hemorrhagic disorders, clinical relevant petechial bleeding, occult blood in feces, hematuria in repeated urine tests(unless attributed to menstruation), trauma or surgery within the last month, planned surgery during trial participation, history of arteriovenous malformation or aneurysm, history of gastroduodenal ulcer disease or gastrointestinal hemorrhage, history of intracranial, intraocular, spinal, retroperitoneal, or atraumatic intraarticular bleeding, use of drugs that may interfere with hemostasis during trial conduct (eg, acetylic salicylic acid or other non-steroidal anti-inflammatory drugs)
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Participant has an active infection or history of infections as follows:
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Acute infection requiring treatment with oral antibiotics, anti-virals, anti-parasitics, anti-protozoal, or anti-fungals within 14 days before the Baseline visit.
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A serious infection, defined as requiring hospitalization or intravenous anti-microbial therapy within 2 months prior to Baseline visit.
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A history of opportunistic, recurrent, or chronic infections.
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Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or antibody to Hepatitis B core antigen (HBcAb) with positive test for HBV DNA (> 500 IU/ml) or hepatitis C antibodies (HCV) at Screening visit.
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Having evidence of active or latent or inadequately treated infection with
Mycobacterium tuberculosis (TB) as defined by the following:
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Positive Interferon Gamma Release Assay (IGRA) (with one of the following acceptable assays: QuantiFERON(R)-TB Gold (QFT-G) test, T-SPOT TB, QuantiFERON-TB Gold In-Tube test (QFT-GIT)) performed during Screening or within 3 months prior to Day 1. OR
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History of either untreated or inadequately treated latent or active TB infection.
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Participants with positive testing for COVID-19 at the Baseline visit.
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Participants with clinically significantly abnormal laboratory values, as determined by the Investigator (or medically qualified designee), including but not limited to:
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Absolute neutrophil count ≤ 1,500/μL or absolute lymphocyte count ≤ 800/μL, or eosinophil count > 700/μL, platelet counts < 100 × 109/L, hemoglobin < ULN, or any abnormal evaluations judged clinically significant by the Investigator (or medically qualified designee) at the Screening or Baseline visits. A single repeat of laboratory tests is permissible at Screening and Baseline, if deemed required by PI or medically qualified designee.
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Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) or alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≥ values of more than 1.5 times the upper limit of normal (ULN), which remains similar upon repeat, at the Screening or Baseline visits.
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Total bilirubin above ULN, which remains similar upon repeat, at the Screening or Baseline visits.
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Participants with Creatinine clearance rate < 80 mL/min as determined by the Cockcroft Gault formula, which remains similar upon repeat, at the Screening or Baseline visits.
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Closure time testing or platelet aggregometry testing (to monitor platelet function) outside of reference range at Screening or Baseline visit.
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QTcF greater than 450 msec (males) or greater than 470 msec (females) at Screening or Baseline visit (if out of range, repeat twice and average the 3 readings for eligibility purposes) or deemed clinically significant by the Investigator (or medically qualified designee).
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Screening ECG with QRS and/or T-wave judged to be unfavorable for a consistently accurate QT measurement as judged by the Investigator (or medically qualified designee).
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Clinically significant abnormal screening values in clinical (electrocardiograms [ECGs], vital signs, physical examination) and laboratory tests in the opinion of the Investigator (or medically qualified designee). Up to two repeats of assessments or tests can be conducted at the discretion of the Investigator (or medically qualified designee).
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Use of any prescription medication within the 14 days prior to the first study drug administration or five half-lives, whichever is longer.
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Use of over-the-counter medication within 7 days prior to the first study drug administration, including herbal medicines, that in the opinion of the Investigator (or medically qualified designee) may make participation unsafe for the participant or interfere with trial evaluations.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Inmagene Biopharmaceuticals
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IMG-004-101