A Phase 2a Study to Evaluate the Safety and Efficacy of Cannabidiol Only as Maintenance Therapy and Steroid Sparing in Patients With Stable Autoimmune Hepatitis

Study Overview
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Brief Summary
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Subjects with stable autoimmune hepatitis disease currently being administered corticosteroids with or without azathioprine (AZA) treatment will be be treated with Cannabidiol instead of standard of care treatment with corticosteroids

Detailed Description
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Patients will be included if they are in stable remission with a prednisone at the lower stable dose to maintain remission with or without azathioprine , Budesonide with or without azathioprine or azathioprine alone for at least 24 months. Patient will be switch from standard of care to treatment with Cannabidiol for 12 months. They will receive increasing doses of Cannabidiol over a period of one month. Dosage will start at 25 mg Cannabidiol twice a day and will be increased every seven days, if no side effects are observed, to 50 mg, 100 mg and finally to 150 mg Cannabidiol twice a day respectively, as detailed below. At the end of this month, if the 150 mg twice a day dose level is deemed safe for one week, the standard of care will be stopped at once and patients will continue receiving only Cannabidiol 150 mg twice a day for an additional period of 11 months. The patient will be offered to undergo liver biopsy in the screening period to prove histological remission along with the biochemical remission (not mandatory for inclusion). After 12 months of treatment with Cannabidiol all patient will undergo liver biopsy for confirmation of histological remission and then the treatment will be stopped as for physician decision and guidelines of treatment of autoimmune hepatitis disease. In any case of flare defined as elevation in liver enzymes and immunoglobulins in consecutive blood test the patient will reintroduced for standard of care treatment at a dosage as of investigator decision and the Cannabidiol will be discontinued. The patient will be withdrawn from the study but will continue follow up until returning to stable inactive disease as define as normalization of liver enzymes and immunoglobulin level in consecutive blood tests.

Official Title
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A Phase 2a Open Label, Single Arm Study to Evaluate the Safety and Efficacy of Cannabidiol Only as Maintenance Therapy and Steroid Sparing in Patients With Stable Autoimmune Hepatitis

Conditions
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Autoimmune Hepatitis

Intervention / Treatment
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* Drug: Cannabidiol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically confirmed chronic hepatitis Age ≥18 years Subject able to provide written informed consent Stable disease for 24 months Currently being administered prednisone (with or without azathioprine) therapy at the lower stable dose to maintain remission or Budesonide (with or without azathioprine) therapy at the lower stable dose to maintain remission or azathioprine alone. ALT ≤ 30 U/L in men and ≤19 U/L in women IgG < 1450 mg/dL Non-pregnant women (via negative pregnancy test) and women with no intention to become pregnant during the term of the trial or three months after cessation of CBD treatment Exclusion Criteria: Viral Hepatitis (HAV, HBV, HCV) HIV Serious psychiatric or psychological disorders Active consumption of illicit drugs including cannabis or derivatives (at least 1 month before study start) Overlap disease with Primary Biliary Cholangitis or Primary Sclerosing Cholangitis IgG4 related Autoimmune Hepatitis Transplant patients Patients with significant cardiac, respiratory or active malignance disease comorbidities. Renal comorbidity: eGFR < 30 mL/min/1.73 m2 (note: CKD Grade 4 is defined as eGFR 15-29 mL/min/1.73 m2) Cirrhosis Patients treated with corticoids for other indication except Autoimmune Hepatitis Patient that are taking immunomodulatory medications for other indication

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sintetic Cannabidiol<br>Synthetic Cannabidiol, dissolved in pharmaceutical grade olive oil at a concentration of 5% will be administered orally twice a day | Drug: Cannabidiol<br>* Synthetic Cannabidiol, dissolved in pharmaceutical grade olive oil at a concentration of 5% will be administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with biochemical and histological remission | biochemical and histological data will be collected during the study | 12 month | 
| Number of patients who experience Cannabidiol relates adverse events | Adverse events will be recorded during the study | 12 month | 
| Proportion of patients with flare up of hepatitis | record of disease flare will be collected during the study | 12 month |