A trial to evaluate safety and characteristics of a substance for treatment of chronic hepatitis

Start 19 Sep 2023 · End 16 Oct 2025 · Status Ended · 1 EU/EEA countries · 3 sites · Protocol RBHB1203

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)

Status Ended

Participants planned 48

Countries 1

Sites 3

Chronic hepatitis B

Key facts

Sponsor: Suzhou Ribo Life Science Co. Ltd.
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Virus Diseases [C02]
Trial duration: 19 Sep 2023 → 16 Oct 2025
Decision date (initial): 2023-05-17
Transition trial: No
Low-intervention: No
Rare-disease indication: No
Vulnerable population: No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

To evaluate the safety and efficacy of RBD1016 injection in participants with CHB on nucleoside analogues (NAs) background treatment.
The trial is a multi-center, randomized, double-blind, placebo-controlled clinical study trial to assess the safety, efficacy, PK and immunogenicity of RBD1016 injection combined with NAs in CHB participants.
The study trial contains screening period, treatment period and follow-up period. The trial is divided into 3 dose groups: 100 mg Q4W, 200 mg Q4W, and 200 mg Q12W. Each group will enroll 16 eligible participants, with 36 participants receiving RBD1016 injection and 12 participants receiving placebo.

Secondary objectives 1

To evaluate other efficacy measures, pharmacokinetic (PK) and immunogenicity of RBD1016 injection in participants with CHB on NAs background treatment.

Conditions and MedDRA coding

Chronic hepatitis B

Version	Level	Code	Term	System organ class
20.1	PT	10008910	Chronic hepatitis B	100000004862

Study design 1 period

#	Title	Allocation	Blinding	Roles blinded	Arms
1	Study design This trial is a multi-center, randomized, double-blind, placebo-controlled clinical trial to assess the safety, efficacy, PK and immunogenicity of RBD1016 injection on NAs background treatment in CHB participants. The trial consists of screening period, treatment period, and FU period. It is divided into 3 dose groups, namely 100 mg Q4W, 200 mg Q4W and 200 mg Q12W. Each group will enroll 16 eligible participants, with 12 participants receiving RBD1016 injection and 4 participants receiving placebo. Participants who sign the informed consent form will undergo screening tests from D-28 to D-1. Those who meet the inclusion criteria and not meet any of the exclusion criteria will return to the trial center at D1. They will be assigned to one of the 3 dose groups in parallel. 100 mg Q4W dose group and 200 mg Q4W dose group will receive corresponding doses of RBD1016 injection or placebo by subcutaneous injection on D1, D29, D57, and D85, and participants in the 200 mg Q12W dose group will receive corresponding doses of RBD1016 injection or placebo by subcutaneous injection on D1 and D85. All CHB participants will take NAs once daily during the trial period. Participants will return to the trial site for relevant efficacy, safety, ADA and PK assessments. The PD assessments are performed at pre-defined timepoints. The ADA assessments are also performed at pre-defined timepoints. The PK assessments are performed according to protocol.	Randomised Controlled	Double	[{"id":130306,"code":5,"name":"Carer"},{"id":130307,"code":1,"name":"Subject"},{"id":130305,"code":2,"name":"Investigator"},{"id":130308,"code":3,"name":"Monitor"},{"id":130309,"code":4,"name":"Analyst"}]	Dose group 1: 100 mg RDB1016 or placebo every fourth week - 4 doses Dose group 3: 200 mg RDB1016 or placebo every fourth week - 4 doses Dose group 2: 200 mg RDB1016 or placebo every twelfth week - 2 doses

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1) Willing and able to give written informed consent for trial participation;
2) Male or female participants aged 18-65 years;
3) Body mass index (BMI) within the range of 18-34 kilograms/square meter (kg/m2);
4) Documented history of chronic hepatitis B virus (HBV) infection, by positive HBsAg and/or HBV DNA tests ≥ 6 months before screening;
5) HBeAg positive or negative at screening;
6) On a stable regimen (≥ 12 months before screening) of any approved first-line oral NAs;
7) HBV DNA level <100 IU/mL at screening;
8) HBsAg level ≥50 IU/mL at screening;
9) Serum/plasma alanine aminotransferase (ALT) ≤ 1.5 times the upper limit of normal (ULN);
10) Liver transient elastography (FibroScan) results within 12 months before screening or at screening showing that the liver stiffness measurement (LSM) level is less than 9 kPa; or with liver biopsy within 24 months before screening showing that the Metavir score is F0-F2;
11) For females with child-bearing potential: must be non-pregnant and non-lactating; the participant is using a highly effective contraceptive method for at least one month before screening and agree contraception during the trial period;
12) For males with child-bearing potential: the participant agrees contraception to ensure effective contraception for his sexual partner during the trial period.

Exclusion criteria 20

1) Laboratory results at screening as follows: serum/plasma alpha-fetoprotein (AFP) >50 μg/L; serum/plasma albumin concentration <3.0 g/dL; international normalized ratio (INR) >1.5; serum/plasma platelet count <90×109/L; serum/plasma direct bilirubin (DB) >2×ULN; serum/plasma creatinine concentration >1.5×ULN or creatinine clearance <60 mL/min (according to the Cockcroft-Gault equation); or any clinically significant laboratory outliers that the investigator believes may interfere with the interpretation of the efficacy and safety data in this trial;
10) Severe mental illness or uncontrolled current mental disorders, including but not limited to schizophrenia, bipolar disorder, or depression, which makes the participant not suitable for trial participation in opinion of the investigator;
11) Abnormal and clinically significant 12-lead ECG test results at screening such as QTcB/QTcF male>470ms, female>480ms, or other clinically significant abnormalities, which makes the participant not suitable for trial participation in opinion of the investigator;
12) Participants who have undergone major surgery within 6 months before screening;
13) Participants with serious infection, trauma or surgery within 4 weeks before screening, or those who plan to undergo surgery during the trial;
14) Participants with severe allergic constitution (allergic to multiple drugs and food), or with clear allergy to this product or its preparation ingredients which makes the participant not suitable for trial participation in opinion of the investigator;
15) History of severe hypersensitivity to subcutaneous injections (mild reactions are allowed, such as local swelling or redness);
16) Use of immunomodulators (thymosin, interleukin-2, levamisole, systemic corticosteroids, etc.) and/or cytotoxic drugs within 6 months prior to screening;
17) Enrollment in any other clinical trial involving drugs within 1 month prior to IMP administration or within 5 half-lives of other drugs, or have previously participated in clinical trials of similar anti-HBV siRNA or antisense oligonucleotide drugs, or have participated in clinical trials of anti-HBV drugs within 6 months before screening (if participants withdraw from that trial before treatment, that is, they are not randomized or receive no treatment, they can be screened in this trial);
18) Excessive alcohol drinking or abuse within 6 months before screening (for males: more than 14 standard units per week, and for females: more than 9 standard units per week. 1 standard unit contains 14 g of alcohol, such as 360 mL of beer or 45 mL of spirits of 40 % alcohol or 150 mL of wine) which in the investigator’s opinion that it is not appropriate to participate in this trial;
19) Drug users/drug abusers at 6 months before screening, and those who are proven to be drug abusers by reasonable evidence (at the discretion of the investigator);
2) Concurrent hepatitis C virus (HCV), human immunodeficiency virus (HIV), or diagnosis of syphilis, acute hepatitis A or acute hepatitis E;
20) Those who the investigator believes are not suitable to participate in the trial due to other factors.
3) Diagnosed with other liver diseases other than hepatitis B, including: autoimmune liver disease (autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis), inherited metabolic liver disease (hemochromatosis, Wilson’s disease, familial intrahepatic cholestasis, etc.), drug-induced liver disease and moderate or above non-alcoholic steatohepatitis (NASH), and the investigator believes that they are not suitable to participate in this trial;
4) History of liver cirrhosis or hepatic decompensation (e.g., ascites, varices bleeding, or hepatic encephalopathy) before or at screening;
5) History of organ transplantation or hepatocellular carcinoma (HCC);
6) History of COVID-19 within one month before screening;
7) Any serious or active disease other than liver disease that the investigator believes may interfere with the participant’s treatment, evaluation or compliance with the trial protocol, including any uncontrolled clinically significant renal, cardiac, pulmonary, thyroid, vascular, neurogenic, digestive, and metabolic disease;
8) History of immune-associated diseases (for example: idiopathic thrombocytopenic purpura, systemic lupus erythematosus, rheumatoid arthritis, autoimmune hemolytic anemia, severe psoriasis, or any other autoimmune disease);
9) History of malignant tumor within 5 years before screening, excluding special tumors cured by surgery (such as basal skin cancer);

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

Primary safety endpoint: Number and percentage of participants with adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESI) up to follow-up (FU) Week 24.
Primary efficacy endpoint: The maximum decline (log value) of HBsAg level from baseline up to FU Week 24.

Secondary endpoints 2

1) The proportion of participants with HBsAg decline ≥1 log10 IU/mL from baseline to FU Week 24;
2) PK parameters for RBD1016 and its metabolites, including but not limited to maximum concentration (Cmax), time to maximum concentration (Tmax), area under curve (AUC0-t, AUC0-inf), elimination half-life (t1/2), terminal rate constant (λz), apparent volume of distribution (Vd/F), apparent clearance (CL/F), steady state concentration (Css) up to FU Week 12.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

RBD1016

PRD10227465 · Product

Active substance: RBD1016
Pharmaceutical form: INJECTION
Route of administration: SUBCUTANEOUS
Max daily dose: 200 mg milligram(s)
Max total dose: 800 mg milligram(s)
Max treatment duration: 12 Week(s)
Authorisation status: Not Authorised
MA holder: SUZHOU RIBO LIFE SCIENCE CO. LTD.
Paediatric formulation: No
Orphan designation: No

Placebo 1

light yellow transparent clear solution, 1 ml per vial, containing 4 μg of vitamin B2 (for coloring purpose only, inactive at this concentration), with the same appearance as RBD1016 injection, for subcutaneous injection.

N/A · Product

Other product name: N/A
Pharmaceutical form: N/A
ATC code: N/A — N/A
Marketing authorisation: N/A
MA holder: N/A
MA country: Iceland
Paediatric formulation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Suzhou Ribo Life Science Co. Ltd.

Sponsor organisation: Suzhou Ribo Life Science Co. Ltd.
Address: No 168 Yuanfeng Road, Kunshan Kunshan
City: Suzhou
Postcode: 215301
Country: China

Scientific contact point

Organisation: Suzhou Ribo Life Science Co. Ltd.
Contact name: Sara Svedlund

Public contact point

Organisation: Suzhou Ribo Life Science Co. Ltd.
Contact name: Sara Svedlund

Locations

1 EU/EEA country · 3 investigational sites

By country

Country	MS status	Planned subjects	Sites
Sweden	Ended	24	3
Rest of world China	—	24	—

Investigational sites

Sweden

3 sites · Ended

Karolinska University Hospital

ME infektionssjukdomar, Halsovagen, Flemingsberg, Huddinge

CTC Clinical Trial Consultants AB

MTC, Dag Hammarskjolds Vag 14, Uppsala Domkyrkofors., Uppsala