A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CB06-036 in Subjects With Chronic Hepatitis B

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Ascending Doses of CB06-036 in Subjects With Chronic Hepatitis B

CB06-036 is an investigational drug developed by Shanghai Zhimeng Biopharma Inc. for the treatment of Chronic Hepatitis B.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Hepatitis b
• Intervention / Treatment: Drug: Placebo; Drug: CB06-036

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Provide written informed consent before any study assessment is performed. 2. Male or nonpregnant, nonlactating female between the ages of 18 and 65 years (inclusive) at screening.

Females of childbearing potential (as defined in Appendix 3) must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline prior to enrollment. and agree to use 2 methods of birth control. Methods must include Protocol CONFIDENTIAL Labcorp Drug Development Study: 000000244098 Protocol Reference: CB06-036-102 Protocol Version 1.0, 24 January 2023 Page 7 of 68 1 highly effective method with a secondary method of birth control during the study and for 3 months following the last dose of CB06-036. These methods are defined in Appendix 3.

Note: Females must agree not to breastfeed during the study and 30 days after receiving the last administration of CB06-036 and not to donate eggs (ova, oocytes) for assisted reproduction during the study and 90 days after receiving the last administration of CB06-036. Females of nonchildbearing potential defined as permanently sterile (ie, due to hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or postmenopausal, as defined in Appendix 3.

Males with a female partner(s) of childbearing potential will agree to use contraception as detailed in Appendix 3. Male subjects must not donate sperm during the study and for at least 90 days after the last administration of CB06-036.

3. Documented evidence of chronic HBV infection (eg, HBsAg positive for more than 6 months) with detectable HBsAg level at screening. Cohort 4 only: qHBsAg should be <3000 IU/mL.

4. Have been on commercially available HBV NA treatment(s) (tenofovir alafenamide, tenofovir disoproxil fumarate, entecavir, either as a single agent or in combination) for at least 6 months with no change in regimen for 3 months prior to screening.

5. HBV DNA <90 IU/mL; measured at least once by local laboratory assessment within 6 months prior to screening.

6. HBV DNA <90 IU/mL at screening. 7. HBeAg Status (Cohorts 1 to 3): HBeAg-positive or negative, Cohort 4 only: HBeAg-negative.

8. Body mass index (BMI) of 18.0 to 32.0 kg/m2 (inclusive), and a total body weight ≥50.0 kg for males and ≥45.0 kg for females at screening.

9. Electrocardiogram (ECG) without clinically significant abnormalities and with QT interval corrected using Fridericia's formula (QTcF) ≤450 msec for males and ≤470 msec for females at screening.

10. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures as specified in the protocol.

Exclusion Criteria:

• 1. CHB patients with extensive bridging fibrosis or cirrhosis (METAVIR ≥3 or Ishak ≥4 by a liver biopsy within 5 years, FibroTest score >0.48 and APRI >1, or a historic FibroScan >9 kPa within 6 months prior to screening).

  2. Subjects met any of the following laboratory parameters at screening:

  1. hemoglobin <12 g/dL (for males) or <11 g/dL (for females)
  2. white blood cell count <2500 cells/mm3 Protocol CONFIDENTIAL Labcorp Drug Development Study: 000000244098 Protocol Reference: CB06-036-102 Protocol Version 1.0, 24 January 2023 Page 8 of 68
  3. neutrophil count <1500 cells/mm3 (or <1000 cells/mm3 if considered a physiological variant in a subject of African descent)
  4. ALT >2 × ULN
  5. INR >ULN unless the subject is stable on an anticoagulant regimen affecting INR
  6. albumin <3.5 g/dL
  7. direct bilirubin >1.5 × ULN
  8. platelet Count <100,000/μL

  9. estimated creatinine clearance (CrCl) <60 mL/min (using the Cockcroft-Gault method).

     3. Active systemic infections (other than common cold) within 2 weeks before randomization.

     4. At screening, known history of lymphoma, leukemia, or malignancy within the past 5 years, except for squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.

     5. History or presence of a medical condition associated with liver disease other than HBV infection (eg, hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposure, thalassemia, nonalcoholic steatohepatitis). Other known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

     6. Personal or family history or symptomatology indicative of a risk of immune-mediated disease (eg, inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis, autoimmune uveitis, multiple sclerosis).

     7. Received solid organ or bone marrow transplant. 8. Received prolonged systemic therapy with immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal antibody, interferon) within 3 months of screening.

     9. Blood donation of approximately 500 mL within 56 days prior to first administration of study drug, plasma from 2 weeks prior to screening, or platelets from 6 weeks prior to screening.

     10. Have a known history of asthma. Note: Subjects with resolved childhood asthma with no history of hospitalization due to asthma are allowed.

     11. Are currently enrolled in, or discontinued from, a clinical trial involving an investigational product or non-approved drug within the last 4 weeks or at least 5 half-lives of the last dosing; or concurrently enrolled in any other types of medical research judged not to be scientifically or medically compatible with this study.

     12. Have had a live vaccination within 12 weeks before randomization, or intend to have a live vaccination during the course of the study, or have participated in a vaccine clinical trial within 12 weeks prior to randomization. Investigators should review the vaccination status of the subjects and follow the local guidelines for adult vaccination Protocol CONFIDENTIAL Labcorp Drug Development Study: 000000244098 Protocol Reference: CB06-036-102 Protocol Version 1.0, 24 January 2023 Page 9 of 68 with non-live vaccines intended to prevent infectious disease prior to first administration of study drug.

     13. Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis D virus (HDV).

     • Subjects who are HCV Ab positive, but have a documented negative HCV RNA, are eligible.

     14. Abnormal clinical laboratory values at screening that, in the opinion of the investigator, pose an unacceptable risk to the subject or of interfering with the interpretation of study results if participating in the study.

     15. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin laboratory test at screening or at Days -7 to -4.

     16. Have any other condition that precludes the subject from following and completing the protocol in the opinion of the investigator.

     17. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, retinal, or psychiatric disorder, as determined by the investigator (or designee).

     18. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed).

     19. Use or intend to use any nonprescription medications or products including vitamins, minerals, and herbal supplements (ie, traditional Chinese medicine), protein powders or fish oils preparations within 7 days prior to screening, considered to potentially impact subject safety or the objectives of the study, as determined by the investigator (or designee).

     20. Alcohol consumption of >21 units per week for males and >14 units for females. One unit of alcohol equals 12 oz (360 mL) beer, 1½ oz (45 mL) liquor, or 5 oz (150 mL) wine.

     21. Ingestion of Seville orange-, or grapefruit-containing foods or beverages within 7 days prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CB06-036 Cohort 1; CB06-036 1.5 mg once weekly	Drug: CB06-036; CB06-036 capsule
Placebo Comparator: Placebo Cohort 1; Placebo 1.5 mg once weeky	Drug: Placebo; Placebo capsule
Experimental: CB06-036 Cohort 2; CB06-036 3.0 mg once weekly	Drug: CB06-036; CB06-036 capsule
Placebo Comparator: Placebo Cohort 2; Placebo 3.0 mg once weekly	Drug: Placebo; Placebo capsule
Experimental: CB06-036 Cohort 3; CB06-036 1.5 mg twice-a-week, for 4 weeks	Drug: CB06-036; CB06-036 capsule
Placebo Comparator: Placebo Cohort 3; Placebo 3.0 mg twice-a-week, for 4 weeks	Drug: Placebo; Placebo capsule
Experimental: CB06-036 Cohort 4; CB06-036 3.0 mg once weekly for 4 weeks	Drug: CB06-036; CB06-036 capsule
Placebo Comparator: Placebo Cohort 4; Placebo 3.0 mg once weekly for 4 weeks	Drug: Placebo; Placebo capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety and tolerability of CB06-036 following multiple oral dose administration of CB06-036 in virally suppressed subjects with CHB.	Number of participants with treatment-related adverse events as assessed by CTCAE V5.0 or higher	From the signing of the consent form until 90 days following the last dose of the study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of CB06-036 following multiple oral dose administration in virally suppressed subjects with CHB.	Plasma will be collected at multiple timepoints from within 30 minutes pre-dose to 24 hours post-dose	From 30 minutes pre-dose to 24 hours post-dose
Area Under the Plasma Concentration Versus Time Curve (AUC) of CB06-036	Plasma will be collected at multiple timepoints from within 30 minutes pre-dose to 24 hours post-dose	From 30 minutes pre-dose to 24 hours post-dose
The following inflammatory cytokines and chemokines will be analyzed in serum: CCL11 (Eotaxin-1), CCL2 (MCP1), CCL20 (MIP3α), CCL4 (MIP1ß), CCL8 (MCP2), CRP, CXCL10 (IP10), CXCL8 (IL-8), CXCL9 (MIG), IFN-γ, IL-12p40, IL-12p70, IL-1RA, SAA, TNF-α	Blood samples will be collected on Day 1 at pre-dose and at 8, 24, 72 hours post-dose of the last dose of study drug	From pre-dose to 72 hours post-dose of the last dose of study drug

Collaborators and Investigators

• Sponsor: Shanghai Zhimeng Biopharma, Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2023
• Primary Completion (Anticipated): March 27, 2024
• Study Completion (Anticipated): March 30, 2024

Study Registration Dates

• First Submitted: April 12, 2023
• First Submitted That Met QC Criteria: April 12, 2023
• First Posted (Actual): April 25, 2023

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 12, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Chronic Hepatitis b
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: CB06-036-102

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