A Study of IMB-101 in Healthy Volunteers and Participants With Rheumatoid Arthritis

A Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Phase 1 Clinical Trial to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of IMB-101 in Healthy Volunteers and Patients With Active Rheumatoid Arthritis (RA)

The primary purpose of this study is to evaluate the safety and tolerability of intravenous (IV) doses of IMB-101 in healthy volunteers and participants with active RA on a stable regimen of methotrexate.

Study Overview

• Status: Not yet recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: IMB-101; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lilly Huh; Phone Number: +82-31-8067-8191; Email: junghyun.huh@imbiologics.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

Phase 1a: Healthy Participants:

1. The participant is 18 to 55 years of age, inclusive, at screening.
2. The participant has a BMI of 18.5 to 32 kilogram per square meter (kg/m^2), inclusive, at screening.
3. The participant is considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead ECG results, and physical examination findings to be not clinically significant at screening.
4. Female participants of childbearing potential must use at least 1 form of highly effective methods of birth control from screening until at least 90 days after last study drug dose; OR be surgically sterile OR be postmenopausal. All female participants of childbearing potential must have a negative pregnancy test at screening and before the first dose of study drug. Female participants must also agree to refrain from egg donation during the study and for at least 90 days after study drug dosing.
5. Male participants must agree to use a condom when sexually active with a female partner of childbearing potential during the study and for at least 90 days after study drug dosing (OR be surgically sterile; OR agree to practice abstinence during the study and for at least 90 days after study drug dosing).
6. The participant agrees to comply with all protocol requirements.
7. The participant is able to provide written informed consent.

Phase 1b: Active RA Participant:

1. The participant is 18 to 65 years of age, inclusive, at screening.
2. The participant has a BMI of 18.5 to 35 kg/m^2, inclusive, at screening.
3. The participant must have a diagnosis of RA based on the 2010 ACR per EULAR criteria for more than 6 months.
4. The participants must have moderate to severe RA characterized as tenderness or pain in at least 6/68 joints with movement and swelling in at least 4/66 joints at screening and baseline.
5. The participants must be on a stable dose of MTX (up to 25 mg per week) for 4 weeks prior to the first dose of study drug and must be able to continue on this stable dose for the duration of the study. Participant must be on a stable, >=5 mg/week dose of oral folic/folinic acid for at least 4 weeks immediately before Day 1.
6. Systemic corticosteroids (<=10 mg/day prednisone equivalent) and NSAIDs are permitted if on a stable dose for at least 4 weeks prior to the first dose of study drug and the participant must be stable for the duration of the study.
7. Female participants of childbearing potential must use at least 1 form of highly effective methods of birth control from screening until at least 90 days after study drug dosing; OR be surgically sterile; OR be postmenopausal. All female participants of childbearing potential must have a negative pregnancy test at screening and before the first dose of study drug.
8. Male participants must agree to use a condom when sexually active with a female partner of childbearing potential during the study and for at least 90 days after study drug dosing (OR be surgically sterile; OR agree to practice abstinence during the study and for at least 90 days after study drug dosing).
9. The participant agrees to comply with all protocol requirements.
10. The participant is able to provide written informed consent.

Key Exclusion Criteria:

Phase 1a: Healthy Participants:

1. The participant has any significant acute or chronic medical illness that, in the opinion of the investigator, would impact the participant's ability to complete all study requirements or that might impact the assessment of study data; or the participant has had a clinically significant illness within 30 days prior to study drug dosing per investigator discretion.
2. The participant has a positive COVID-19 molecular diagnostic test result at screening or prior to study drug dosing; or the participant has known or suspected current sequelae from a prior episode of COVID-19.
3. The participant has had major surgery, as determined by the investigator, within 12 weeks prior to study drug dosing.

4. The participant has any of the following prior to study drug dosing:

   • Systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg.

5. The participant has any of the following on 12-lead ECG prior to study drug dosing, confirmed by repeat:

   • Heart rate <40 or >100 beats per minute.
   • PR interval >220 milliseconds (ms).
   • QRS width >120 ms.
   • QTcF >=450 ms (male) or >=470 ms (female).

6. The participant has any of the following clinical laboratory results at screening, confirmed by repeat:

   • WBCs, lymphocytes, or neutrophil counts outside site acceptable ranges per site SOPs.
   • Calculated creatinine clearance <60 mL (the CKD-EPI formula)
   • ALT or AST >2*ULN
   • Total bilirubin >2*ULN
7. The participant has a positive test result for HBsAg, anti-HBcAb, hepatitis C virus antibody, or HIV types 1 or 2 antibodies at screening.
8. The participant has a history of TB, active TB, or a positive Quantiferon-TB Gold Plus (QFT-Plus) test at screening.
9. The participant has received any vaccine or used any prescription or over the-counter medications (except acetaminophen [up to 2 g per day]), including herbal or nutritional supplements, within 14 days prior to study drug dosing.
10. The participant has received biologic agents within the 3 months prior to study drug dosing, or 5 half-lives, whichever is greater. Participants with a prior history of anti-TNFα exposure will be excluded.
11. The participant is a smoker or has regularly used nicotine or nicotine-containing products within 3 months prior to study drug dosing.
12. History of drug abuse within 1 year prior to screening.
13. The participant has a positive test result for drugs of abuse, alcohol, or cotinine (indicating active current smoking) at screening or prior to study drug dosing.
14. The participant has donated blood or blood products >500 mL within 30 days prior to study drug dosing.
15. The participant has a history of hypersensitivity to vaccines, the study drug, or to drugs of similar chemical classes including allergy to drug or its excipients.
16. Any reason which, in the opinion of the Investigator, would prevent the participant from participating in the study.

Phase 1b: Active RA Participant:

1. The participant having RA functional status class IV according to the ACR 1991 revised criteria.
2. The participant diagnosed with any other inflammatory arthritis or systemic inflammatory disease (eg, gout, psoriatic or reactive arthritis, Crohn's disease, Lyme disease, juvenile idiopathic arthritis, or systemic lupus erythematosus). Secondary Sjogren's syndrome is not exclusionary.
3. The participant received treatment with any oral DMARDs other than MTX within 4 weeks prior to baseline. Leflunomide should be discontinued at least 8 weeks prior to baseline.
4. The participant has used anti-TNF or other biologic DMARDs in the 3 months prior to baseline (or 5 half-lives, whichever is longer).
5. The participant has adalimumab drug levels or NAbs to adalimumab or detected at screening.
6. The participant received any intra-articular injection therapy for treatment of acute RA flare within 4 weeks before baseline.
7. The participant received IV steroids, immunosuppressants, investigational drugs, and oral anticoagulant or antiplatelet drugs within 4 weeks prior to randomization.
8. The participant has received previous treatment with a B cell-depleting biologic agent or any other immunomodulatory biologic agent within 5 half-lives.
9. The participant has received prior treatment with cyclophosphamide.
10. The participant requires chronic treatment with opioid analgesics within 4 weeks prior to baseline.
11. The participant has received concomitant medication with a half-life >24 hours within 4 weeks prior to baseline (or 10 half-lives, whichever is longer).
12. The participant is a smoker or has regularly used nicotine or nicotine-containing products within 3 months prior to study drug dosing.
13. The participant has a positive test result for drugs of abuse, alcohol, or cotinine (indicating active current smoking) at screening or prior to study drug dosing.
14. The participant with active TB or a history of TB, or a positive Quantiferon-TB Gold Plus (QFT-Plus) test at screening.
15. The participant has a history and/or current presence of a clinically significant atopic allergy, hypersensitivity, or allergic reactions, also including known or suspected clinically relevant drug hypersensitivity to any components of the test and reference investigational product formulation or comparable drugs.
16. The participant has a history of any infection requiring hospitalization, IV antibiotics, or as otherwise judged clinically significant, within the 3 months prior to screening, or an opportunistic infection within the past 12 months.
17. The participant has a history of malignancy.
18. The participant has a history of NYHA Class III or IV heart failure.

19. The participant has any of the following prior to study drug dosing, confirmed by repeat:

    • Systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg.

20. The participant has any of the following on 12-lead ECG prior to study drug dosing, confirmed by repeat:

    • Heart rate <40 or >100 beats per minute.
    • PR interval >220 ms.
    • QRS width >120 ms.
    • QTcF >=450 ms (male) or >=470 ms (female).

21. The participant has any of the following clinical laboratory results at screening, confirmed by repeat:

    • WBCs, lymphocytes, or neutrophil counts outside the site acceptable ranges per site SOPs.
    • Calculated creatinine clearance <60 mL (the CKD-EPI formula).
    • ALT or AST >2*ULN.
    • Total bilirubin >2*ULN.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a, Single Ascending Doses (SAD) Cohorts: IMB-101 or Placebo; Healthy participants will receive either planned dose levels of IMB-101 or placebo through a single intravenous administration.	Drug: IMB-101; Intravenous administration.; Drug: Placebo; Matching-placebo intravenous administration.
Experimental: Phase 1b, Multiple Ascending Dose (MAD) Cohorts: IMB-101 or Placebo; Participants with RA will either receive multiple doses of IMB-101 or placebo through multiple intravenous administration once every 2 weeks for up to 10 weeks.	Drug: IMB-101; Intravenous administration.; Drug: Placebo; Matching-placebo intravenous administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	The TEAEs are defined as events that started after the first dose of trial treatment or events present prior to the first dose of study drug but increased in severity after the first dose based on preferred term, including clinically relevant abnormal laboratory findings. An SAE is defined as any event that either results in death, is immediately life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.	From the first dose of study drug up to Day 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a and 1b: Maximum Serum Concentration (Cmax) of IMB-101		Phase 1a: From Day 1 prior to the first dose of study drug up to Day 71; Phase 1b: From Day 1 prior to the first dose of study drug up to Day 85
Phase 1a and 1b: Time to Reach the Maximum Serum Concentration occurred (tmax) of IMB-101		Phase 1a: From Day 1 prior to the first dose of study drug up to Day 71; Phase 1b: From Day 1 prior to the first dose of study drug up to Day 85
Phase 1a and 1b: Area Under the Serum Concentration-time Curve From Time Zero to Dosing Interval (AUC0-tau) of IMB-101		Phase 1a: From Day 1 prior to the first dose of study drug up to Day 71; Phase 1b: From Day 1 prior to the first dose of study drug up to Day 85
Phase 1a and 1b: Area Under the Serum Concentration-time Curve From Time Zero to Time (AUC0-t) of IMB-101		Phase 1a: From Day 1 prior to the first dose of study drug up to Day 71; Phase 1b: From Day 1 prior to the first dose of study drug up to Day 85
Phase 1a and 1b: Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of IMB-101		Phase 1a: From Day 1 prior to the first dose of study drug up to Day 71; Phase 1b: From Day 1 prior to the first dose of study drug up to Day 85
Phase 1a and 1b: Serum Elimination Half-life (t1/2) of IMB-101		Phase 1a: From Day 1 prior to the first dose of study drug up to Day 71; Phase 1b: From Day 1 prior to the first dose of study drug up to Day 85
Phase 1a and 1b: Serum Elimination Rate Constant (λz) of IMB-101		Phase 1a: From Day 1 prior to the first dose of study drug up to Day 71; Phase 1b: From Day 1 prior to the first dose of study drug up to Day 85
Phase 1a and 1b: Clearance (CL) of IMB-101		Phase 1a: From Day 1 prior to the first dose of study drug up to Day 71; Phase 1b: From Day 1 prior to the first dose of study drug up to Day 85
Phase 1a and 1b: Volume of Distribution (Vz) of IMB-101		Phase 1a: From Day 1 prior to the first dose of study drug up to Day 71; Phase 1b: From Day 1 prior to the first dose of study drug up to Day 85
Phase 1a and 1b: Accumulation ratio Based on Cmax (Rac[Cmax]) of IMB-101	Rac(Cmax) will be calculated as Cmax after multiple doses divided by Cmax after a single dose.	Phase 1a: From Day 1 prior to the first dose of study drug up to Day 71; Phase 1b: From Day 1 prior to the first dose of study drug up to Day 85
Phase 1a and 1b: Accumulation Ratio Based on Area Under the Concentration-time Curve (Rac[AUC]) of IMB-101	Rac(AUC) will be calculated as AUCtau multiple doses divided by AUCtau after a single dose.	Phase 1a: From Day 1 prior to the first dose of study drug up to Day 71; Phase 1b: From Day 1 prior to the first dose of study drug up to Day 85
Phase 1a and 1b: Trough Serum Concentration (Ctrough) of IMB-101		Phase 1a: From Day 1 prior to the first dose of study drug up to Day 71; Phase 1b: From Day 1 prior to the first dose of study drug up to Day 85
Percentage of Participants With Presence of Antidrug Antibody (ADAs)	The formation of ADAs against IMB-101 will be assessed in blood samples collected from all participants at the indicated time points.	From the first dose of study drug up to Day 85
Number of ADA Positive Participants With Presence of Low and High ADA Titers	Low and high ADA titers will be assessed in ADA positive participants.	From the first dose of study drug up to Day 85
Phase 1b: Cytokine/Chemokine Interleukins Serum Post-dose Levels	Serum levels of Interleukins will be assessed.	Phase 1b: From the first dose of study drug up to Day 85
Phase 1b: TNF-α Serum Post-dose Levels	Serum level Tumor necrosis factor- alpha (TNF-α) will be assessed.	Phase 1b: From the first dose of study drug up to Day 85
Phase 1b: Receptor Activator of Nuclear Factor Kappa Beta Ligand (RANKL) Serum Post-dose Levels	RANKL Serum level will be assessed.	Phase 1b: From the first dose of study drug up to Day 85

Collaborators and Investigators

• Sponsor: IMBiologics Corp.

Study record dates

Study Major Dates

• Study Start (Estimated): December 13, 2023
• Primary Completion (Estimated): December 11, 2025
• Study Completion (Estimated): December 11, 2025

Study Registration Dates

• First Submitted: December 13, 2023
• First Submitted That Met QC Criteria: December 13, 2023
• First Posted (Actual): December 26, 2023

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Rheumatoid Arthritis; Pharmacodynamics; IMB-101; OX40L/TNF bispecific antibody
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: IMB101-CR-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No