Efficacy and Safety of Orally Administered DS102 in Patients With Acute Alcoholic Hepatitis

NCT03452540 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: DS102A-05-AH12018-000819-25
• Study Type: interventional
• Target: 9
• Locations: 2 countries
• Sites: 8

Brief Summary

The purpose of this randomised, double-blind, placebo-controlled, phase II study is to assess the efficacy and safety of orally administered DS102 in adult patients with acute decompensated alcoholic hepatitis

Conditions

Severe Acute Decompensated Alcoholic Hepatitis

Outcome Measures

Primary Outcomes (2)

• Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and SUSARs.

  To evaluate the safety of orally administered DS102 in the treatment of adult patients with severe acute decompensated AH.

  Up to 28 days.

• Descriptive Statistics for Plasma Total 15(S)-HEPE and Unesterified 15(S)-HEPE Pharmacokinetic Results for 1000 mg BD DS102 Administered Orally Twice-daily to Patients With Alcoholic Hepatitis

  Descriptive Statistics for Plasma Total 15(S)-HEPE and Unesterified 15(S)-HEPE Pharmacokinetic Results for 1000 mg BD DS102 Administered Orally Twice-daily to Patients with Alcoholic Hepatitis.

  Up to 7 days

Study Arms (1)

1000mg DS102 (BID)

EXPERIMENTAL

Participants assigned to the open label pilot phase received 1000mg DS102 (BID)for 28 days.

Drug: 1000mg DS102 (BID)

Interventions

1000mg DS102 (BID) DRUG

Participants assigned to the open label pilot phase received 1000mg DS102 (BID)for 28 days.

1000mg DS102 (BID)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged 18 years and older
• Total bilirubin of ≥ 5 mg/dl (85μmol/l)
• Patients with definite or probable AH
• MELD ≥18 at baseline visit
• MDF ≥32 at baseline visit
• AST ≥50 U/L
• AST':ALT ratio \> 1.5
• Female patients, or female partners of male patients, of child bearing potential must use highly effective birth control methods or have a sterilised partner for the duration of the study. Highly effective birth control methods are defined as methods that can achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include intrauterine device or sexual abstinence.
• Note: A woman is considered of child bearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy Note: Hormonal contraceptives are contraindicated in patients with severe hepatic diseases and are not acceptable as a birth control method in this study Note: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject
• Patient and/or legally authorised representative must provide informed consent
• Able to swallow the provided study medication
• Not eligible for liver transplant during this hospitalisation

You may not qualify if:

• Pregnant or lactating females.
• Spontaneous liver function improvement defined by decrease of bilirubin level and MDF of \>10% within 5 days of hospital admission
• Grade 4 hepatic encephalopathy (West Haven Criteria)
• Type 1 hepatorenal syndrome (HRS) or a serum creatinine \>2 x ULN or the requirement for haemodialysis
• History of hypersensitivity to any substance in DS102 capsules or placebo capsules.
• Alcohol abstinence of \>6 weeks prior to screening
• Duration of clinically apparent jaundice \>3 months prior to baseline
• Other causes of liver disease including:
• Evidence of chronic viral hepatitis (Hepatitis B DNA positive or HCV RNA positive)
• Biliary obstruction
• Hepatocellular carcinoma
• Wilsons disease
• Budd Chiari Syndrome
• Non-alcoholic fatty liver disease
• History of or active non-liver malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas).

Sponsors & Collaborators

• Afimmune: lead

Study Sites (8)

Schiff Center for Liver Diseases (University Hospital Miami)

Miami, Florida, 33136, United States

Location

Cleveland Clinic Florida

Miami, Florida, 33331, United States

Location

Kansas University Medical Center

Kansas City, Kansas, 66160, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Bon Secours Liver Institute of Richmond and Bon Secours Liver Institute of Hampton Roads

Newport News, Virginia, 23602, United States

Location

Batumi Referral Hospital

Batumi, Georgia

Location

Saint Nikolozi Surgery Center

Kutaisi, Georgia

Location

MeSH Terms

Interventions

BID protein, human

Limitations and Caveats

Early termination - The study was stopped at the end of the pilot phase (n=9) as the sponsor prioritised other therapeutic indications, so no patients were enrolled in the double-blind phase.

Results Point of Contact

• Title: Study Director
• Organization: Afimmune

regulatory.afimmune@afimmune.com

+353 1 2946380

Study Officials

• Mark Thursz

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2018
• First Posted: March 2, 2018
• Study Start: November 28, 2018
• Primary Completion: June 19, 2019
• Study Completion: March 31, 2020
• Last Updated: July 29, 2022
• Results First Posted: July 29, 2022

Record last verified: 2022-07

Locations

GE (2); US (6)