A Prospective, Randomized, Double-Blind, Placebo-controlled, Multicentric, Comparative, Two-arm followed by an Open-Label, Single arm Clinical Study to Evaluate the Safety and Efficacy of HDLD-092320 in Participants with Drug Induced Liver Injury (DILI)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 120
- 试验地点
- 7
- 主要终点
- Treatment Phase:
研究概览
简要总结
The study is divided into two phases, Treatment phase and Adjuvant phase.
Treatment phase: This will be a randomized, double-blind, placebo-controlled, comparative, two-arm clinical study. Participants will be examined for eligibility criteria during the screening period (within 7 days prior to randomization). After signing the informed consent form, participants who fulfill the eligibility criteria will be enrolled into the study. A total of 120 participants will be enrolled to have at least 100 evaluable participants. Attempt would be made to enroll at least 20 participants in respective category (Antitubercular, Antiretroviral, Anticonvulsant and Analgesics) of DILI causing drugs. Eligible participants will be randomized into either of the treatment arms, i.e., Arm 1 or Arm 2 in 1:1 ratio.
Adjuvant phase: This will be an open-label single-arm study. Drug causing DILI will be reinitiated with same dose or dose titration along with HDLD-092320 for all the subjects as per the discretion of investigator based on LFT parameters/clinical conditions. Participants who are required to take alternative drugs for reinitiation in the adjuvant phase should be withdrawn from the study based on the discussion with investigator and sponsor.
Study End Points:
Efficacy Endpoint: (Treatment Phase) 1. Reduction in Serum ALT, AST, ALP, TBil, INR on day 14 (±3 days) of treatment. 2. Percentage of participants with normalization of serum ALT, AST, ALP, TBil, on day 7(±3 days) and serum ALT, AST, ALP, TBil, INR on day 14 (±3 days) of treatment. 3. Improvement in liver injury symptoms using liver injury symptom evaluation scale.
Efficacy Endpoint: (Adjuvant Phase) 1. Percentage of participants with normalization/non-significant LFT parameters (Serum ALT, AST, ALP, TBil, INR) throughout the adjuvant phase (at various visits).
- Proportion of participants with recurrence of DILI as per LFT assessment (Serum ALT, AST, ALP, TBil, INR) during adjuvant phase. 3. Assessment of liver injury symptoms using liver injury symptom evaluation scale. 4. Assessment of Gastrointestinal Symptom Rating Scale (GSRS). 5. Assessment of quality of life using questionnaires.
Safety Endpoint: 1. Incidence of adverse events during the study period. 2. Proportion of participants withdrawn from trial because of adverse events (tolerability).
Study Visits: There will be a total of 10 study visits for each participant.
Treatment Visits (T-V)
Treatment-Visit 1/ (T-V1)/ (Day -7 to Day 0): Screening Visit
Treatment-Visit 2/ (T-V2)/ (Day 1): Baseline/ Enrollment and Randomization
Treatment-Visit 3/ (T-V3)/ Day 7 (±3 days window period): Local Safety Assessment
Treatment-Visit 4/ (T-V4)/ Day 14 (±3 days window period): End of treatment visit
Adjuvant Visits (A-V):
Drug causing DILI will be reinitiated with same dose or dose titration after T-V4/Day 14, as per the discretion of investigator based on LFT parameters/clinical conditions. Participants who are required to take alternative drugs for reinitiation in the adjuvant phase should be withdrawn from the study based on the discussion with investigator and sponsor.
The maximum gap between end of treatment phase and start of adjuvant phase should be within 14 days.
Adjuvant-Visit1/(A-V1)/Day1: Start of adjuvant visit
Adjuvant-Visit 2/ (A-V 2)/ Day 7 (±2 days window period): Local Safety Assessment
Adjuvant-Visit 3/ (A-V 3)/ Day 14 (±3 days window period): Follow-Up Visit
Adjuvant-Visit 4/ (A-V 4)/Day 28 (±3 days window period): Local Safety Assessment
Adjuvant-Visit 5/ (A-V 5)/ Day 42 (±3 days window period): Follow-Up Visit
Adjuvant-Visit 6/ (A-V 6)/ Day 56 (±3 days window period): End of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Adult male and female participants aged between 18 and 65 years.
- •Participants diagnosed with DILI as defined by any one of the following: (a) serum AST or ALT More than 5 times upper limit of normal (ULN) or ALP More than 2 times ULN (or pretreatment baseline if baseline is abnormal) on two separate occasions at least 24 h apart (b) total serum bilirubin More than 2.5 mg/dl along with elevated serum AST, ALT, or ALP level or (c) INR More than 1.5 with elevated serum AST, ALT, or ALP.
- •3.Participants with mild (1+) to moderate (2+) cases of DILI as per Drug-Induced Liver Injury Network(DILIN).
- •Roussel Uclaf Causality Assessment Method (RUCAM) score more than or equal to 3 points.
- •Participants whose treatment regimen (Antitubercular, Antiretroviral, Anticonvulsant and Analgesics) are expected to use at least 3 months from the date of enrollment.
- •6.Participants who have not participated in any other similar clinical study within the last 3 months of screening.
- •Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.
- •Note: A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: a.
- •Has not undergone a hysterectomy or bilateral oophorectomy; or b.
- •8.Male participants who are willing to refrain from donating sperm from first admission to the study until 90 days after the study completion.
- •9.Participants willingly sign informed consent and follow the study procedure.
排除标准
- •1.Participants with acute viral, autoimmune, alcoholic and non-alcoholic fatty liver disease, or other types of hepatitis.
- •Acute liver failure or liver function decompensation, such as hepatic encephalopathy, ascites for duration less than 26 weeks.
- •3.Known case of Hepatitis A Virus (HAV), Hepatitis B Virus (HBV), Hepatitis C Virus(HCV), Hepatitis E Virus HEV).
- •4.History of Cirrhosis or its complications (like HCC, Portal HTN, Liver failure).
- •Complications may involve: a.
- •Participants listed for living-related or orthotopic liver transplantation b.
- •Participants with a history of hepatocellular carcinoma (HCC) or history of HCC treatment.
- •Evidence of portal hypertension (e.g., low platelet counts, esophageal varices, ascites, history of hepatic encephalopathy, splenomegaly.
- •Other organ failure due to DILI.
- •Other causes of Steatosis (Wilson Disease, Medications, Severe malnutrition).
- •Other laboratory parameters a.
- •Anemia (Hb less than 8gm/dl) or thrombocytopenia (platelet count below 50,000 platelets per microliter) b.
- •Serum creatinine is more than 1.5 times ULN 7.Participants with uncontrolled clinically significant serious conditions like severe anemia, severe cardiovascular disease, respiratory, hepatic, neurological, psychiatric, or malignancy/bleeding disorder or other major systemic disease or participants with short life expectancy that, according to the Investigator, will preclude their safe participation in this study, or will make implementation of the protocol or interpretation of the study results difficult.
- •8.Participants with severe DILI (grade 3+, 4+, 5+) as diagnosed with DILI-N 9.Any other conditions (physical, psychological, or social) that can interfere with the participant’s compliance to the study in the opinion of the Investigator.
- •10.Pregnant, as assessed by UPT & history of amenorrhea or lactating women.
结局指标
主要结局
Treatment Phase:
时间窗: Treatment Phase: | Treatment Visits (T-V) | Treatment-Visit 1/ (T-V1) / (Day -7 to Day 0): Screening Visit | Treatment-Visit 2/ (T-V2)/ (Day 1): Baseline/ Enrollment & Randomization | Treatment-Visit 3/ (T-V3)/ Day 7 (±3 days window period): Local Safety Assessment | Treatment-Visit 4/ (T-V4)/ Day 14 (±3 days window period): End of treatment visit. | Adjuvant Phase: | Adjuvant-Visit1/(A-V1)/Day1: Start of adjuvant visit | Adjuvant-Visit 2/ (A-V 2)/ Day 7 (±2 days window period): Local Safety Assessment | Adjuvant-Visit 3/ (A-V 3)/ Day 14 (±3 days window period): Follow-Up Visit | Adjuvant-Visit 4/ (A-V 4)/Day 28 (±3 days window period): Local Safety Assessment | Adjuvant-Visit 5/ (A-V 5)/ Day 42 (±3 days window period): Follow-Up Visit | Adjuvant-Visit 6/ (A-V 6)/ Day 56 (±3 days window period): End of the study
1. Reduction in Serum ALT, AST, ALP, TBil, INR on day 14 (±3 days) of treatment.
时间窗: Treatment Phase: | Treatment Visits (T-V) | Treatment-Visit 1/ (T-V1) / (Day -7 to Day 0): Screening Visit | Treatment-Visit 2/ (T-V2)/ (Day 1): Baseline/ Enrollment & Randomization | Treatment-Visit 3/ (T-V3)/ Day 7 (±3 days window period): Local Safety Assessment | Treatment-Visit 4/ (T-V4)/ Day 14 (±3 days window period): End of treatment visit. | Adjuvant Phase: | Adjuvant-Visit1/(A-V1)/Day1: Start of adjuvant visit | Adjuvant-Visit 2/ (A-V 2)/ Day 7 (±2 days window period): Local Safety Assessment | Adjuvant-Visit 3/ (A-V 3)/ Day 14 (±3 days window period): Follow-Up Visit | Adjuvant-Visit 4/ (A-V 4)/Day 28 (±3 days window period): Local Safety Assessment | Adjuvant-Visit 5/ (A-V 5)/ Day 42 (±3 days window period): Follow-Up Visit | Adjuvant-Visit 6/ (A-V 6)/ Day 56 (±3 days window period): End of the study
2.Percentage of participants with normalization of serum ALT, AST, ALP, TBil, on day 7(±3 days) and serum ALT, AST, ALP, TBil, INR on day 14 (±3 days) of treatment.
时间窗: Treatment Phase: | Treatment Visits (T-V) | Treatment-Visit 1/ (T-V1) / (Day -7 to Day 0): Screening Visit | Treatment-Visit 2/ (T-V2)/ (Day 1): Baseline/ Enrollment & Randomization | Treatment-Visit 3/ (T-V3)/ Day 7 (±3 days window period): Local Safety Assessment | Treatment-Visit 4/ (T-V4)/ Day 14 (±3 days window period): End of treatment visit. | Adjuvant Phase: | Adjuvant-Visit1/(A-V1)/Day1: Start of adjuvant visit | Adjuvant-Visit 2/ (A-V 2)/ Day 7 (±2 days window period): Local Safety Assessment | Adjuvant-Visit 3/ (A-V 3)/ Day 14 (±3 days window period): Follow-Up Visit | Adjuvant-Visit 4/ (A-V 4)/Day 28 (±3 days window period): Local Safety Assessment | Adjuvant-Visit 5/ (A-V 5)/ Day 42 (±3 days window period): Follow-Up Visit | Adjuvant-Visit 6/ (A-V 6)/ Day 56 (±3 days window period): End of the study
Adjuvant Phase:
时间窗: Treatment Phase: | Treatment Visits (T-V) | Treatment-Visit 1/ (T-V1) / (Day -7 to Day 0): Screening Visit | Treatment-Visit 2/ (T-V2)/ (Day 1): Baseline/ Enrollment & Randomization | Treatment-Visit 3/ (T-V3)/ Day 7 (±3 days window period): Local Safety Assessment | Treatment-Visit 4/ (T-V4)/ Day 14 (±3 days window period): End of treatment visit. | Adjuvant Phase: | Adjuvant-Visit1/(A-V1)/Day1: Start of adjuvant visit | Adjuvant-Visit 2/ (A-V 2)/ Day 7 (±2 days window period): Local Safety Assessment | Adjuvant-Visit 3/ (A-V 3)/ Day 14 (±3 days window period): Follow-Up Visit | Adjuvant-Visit 4/ (A-V 4)/Day 28 (±3 days window period): Local Safety Assessment | Adjuvant-Visit 5/ (A-V 5)/ Day 42 (±3 days window period): Follow-Up Visit | Adjuvant-Visit 6/ (A-V 6)/ Day 56 (±3 days window period): End of the study
1. Percentage of participants with normalization/non-significant LFT parameters(Serum ALT, AST, ALP, TBil, INR) throughout the adjuvant phase (at various visits).
时间窗: Treatment Phase: | Treatment Visits (T-V) | Treatment-Visit 1/ (T-V1) / (Day -7 to Day 0): Screening Visit | Treatment-Visit 2/ (T-V2)/ (Day 1): Baseline/ Enrollment & Randomization | Treatment-Visit 3/ (T-V3)/ Day 7 (±3 days window period): Local Safety Assessment | Treatment-Visit 4/ (T-V4)/ Day 14 (±3 days window period): End of treatment visit. | Adjuvant Phase: | Adjuvant-Visit1/(A-V1)/Day1: Start of adjuvant visit | Adjuvant-Visit 2/ (A-V 2)/ Day 7 (±2 days window period): Local Safety Assessment | Adjuvant-Visit 3/ (A-V 3)/ Day 14 (±3 days window period): Follow-Up Visit | Adjuvant-Visit 4/ (A-V 4)/Day 28 (±3 days window period): Local Safety Assessment | Adjuvant-Visit 5/ (A-V 5)/ Day 42 (±3 days window period): Follow-Up Visit | Adjuvant-Visit 6/ (A-V 6)/ Day 56 (±3 days window period): End of the study
2. Proportion of participants with recurrence of DILI as per LFT assessment (Serum ALT, AST, ALP, TBil, INR) during adjuvant phase.
时间窗: Treatment Phase: | Treatment Visits (T-V) | Treatment-Visit 1/ (T-V1) / (Day -7 to Day 0): Screening Visit | Treatment-Visit 2/ (T-V2)/ (Day 1): Baseline/ Enrollment & Randomization | Treatment-Visit 3/ (T-V3)/ Day 7 (±3 days window period): Local Safety Assessment | Treatment-Visit 4/ (T-V4)/ Day 14 (±3 days window period): End of treatment visit. | Adjuvant Phase: | Adjuvant-Visit1/(A-V1)/Day1: Start of adjuvant visit | Adjuvant-Visit 2/ (A-V 2)/ Day 7 (±2 days window period): Local Safety Assessment | Adjuvant-Visit 3/ (A-V 3)/ Day 14 (±3 days window period): Follow-Up Visit | Adjuvant-Visit 4/ (A-V 4)/Day 28 (±3 days window period): Local Safety Assessment | Adjuvant-Visit 5/ (A-V 5)/ Day 42 (±3 days window period): Follow-Up Visit | Adjuvant-Visit 6/ (A-V 6)/ Day 56 (±3 days window period): End of the study
次要结局
- Treatment Phase-(1.Improvement in liver injury symptoms using liver injury symptom evaluation scale.)
研究者
Dr Manish Kumar Singh
Maya Hospital and Maternity Centre