Severe Acute Decompensated Alcoholic HepatitisPhase 2NCT03452540

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

A Phase 2 study testing 1000mg DS102 (BID) in people with Severe Acute Decompensated Alcoholic Hepatitis, run by Afimmune at 8 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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 Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Severe Acute Decompensated Alcoholic Hepatitis
What is being tested?: 1000mg DS102 (BID)
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 9 participants
Where: 8 sitesin 2 countries
Study dates: 28 Nov 2018to 31 Mar 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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

Who cannot join

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

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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).
Previous entry into the study
AST >400 U/L or ALT >270 U/L
Treatment with any experimental drug within 30 days prior to Day 0 visit (Baseline), or 5 half-lives (whichever is longer).
Patients who have used dietary supplements rich in omega-3 or omega-6 fatty acids in the four weeks prior to baseline.
Patients dependent on inotropic support (adrenaline or noradrenaline), including Terlipressin
Active variceal haemorrhage on this admission requiring more than 2 units of blood to maintain haemoglobin level within 48 hours
Presence of refractory ascites
Untreated or unresolved sepsis
Patients with cerebral haemorrhage, extensive retinal haemorrhage, acute myocardial infarction (within last 6 weeks) or severe cardiac arrhythmias (not including atrial fibrillation)
Known infection with HIV at screening.
Significant systemic or major illnesses other than liver disease that, in the opinion of the investigator, would preclude or interfere with treatment with DS102 and/or adequate follow up.
Previous liver transplantation

Trial locations and contacts

8 sites in 2 countries.

Country

City, postcode or hospital

8 sites in 2 countries

United States6 sites

Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Medical University of South Carolina
Charleston, South Carolina, 29425
Kansas University Medical Center
Kansas City, Kansas, 66160
Schiff Center for Liver Diseases (University Hospital Miami)
Miami, Florida, 33136
Cleveland Clinic Florida
Miami, Florida, 33331
Bon Secours Liver Institute of Richmond and Bon Secours Liver Institute of Hampton Roads
Newport News, Virginia, 23602

Other trials in United States

Georgia2 sites

Batumi Referral Hospital
Batumi
Saint Nikolozi Surgery Center
Kutaisi

Other trials in Georgia

About this study

Official title: A Randomised, Double-Blind, Placebo-Controlled, Phase II Study to Assess the Efficacy and Safety of Orally Administered DS102 in Patients With Acute Decompensated Alcoholic Hepatitis.

Conditions: Severe Acute Decompensated Alcoholic Hepatitis
Being tested: 1000mg DS102 (BID)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT03452540
Study group	Role	What they receive
1000mg DS102 (BID)	Experimental	Participants assigned to the open label pilot phase received 1000mg DS102 (BID)for 28 days. Receives: Drug: 1000mg DS102 (BID)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: Up to 7 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Nov 201831 Mar 2020

First posted2 Mar 2018
Study start28 Nov 2018
Primary completion19 Jun 2019
Study completion31 Mar 2020

Why it stopped: Company Decision

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Severe Acute Decompensated Alcoholic HepatitisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 9 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03452540
Sponsor's protocol ID: DS102A-05-AH1
Other IDs: 2018-000819-25, 2018
Status last verified: Jul 2022
First submitted: 26 Feb 2018
Last updated: 29 Jul 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Study at a glance

From the registry record, last updated by the sponsor on 29 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomised, Double-Blind, Placebo-Controlled, Phase II Study to Assess the Efficacy and Safety of Orally Administered DS102 in Patients With Acute Decompensated Alcoholic Hepatitis.
ClinicalTrials.gov ID: NCT03452540
Acronym / sponsor ID: DS102A-05-AH1
Conditions: Severe Acute Decompensated Alcoholic Hepatitis
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Company Decision
Enrolment: 9 participants (actual)
Lead sponsor: AfimmuneIndustry (pharma, biotech, devices)
Study start: 28 Nov 2018 (actual)
Primary completion: 19 Jun 2019 (actual)
Study completion: 31 Mar 2020 (actual)
First posted: 2 Mar 2018 (actual)
Results: Posted 29 Jul 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
1000mg DS102 (BID)	Experimental	Drug: 1000mg DS102 (BID)Participants assigned to the open label pilot phase received 1000mg DS102 (BID)for 28 days.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

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

Key exclusion criteria (27 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

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

Primary outcome

Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and SUSARs.
Time frame: Up to 28 days.
To evaluate the safety of orally administered DS102 in the treatment of adult patients with severe acute decompensated AH.
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
Time frame: Up to 7 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.

Results and safety

Results posted to the registry on 29 Jul 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
1000mg DS102 (BID)	9	5

Primary outcome: Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and SUSARs.

Time frame: Up to 28 days.. Number. Unit: Number of Events

Measure	1000mg DS102 (BID) n = 9
Total Number of TEAEs	7
Total Number of Serious TEAEs	4
Total Number of Serious Treatment Related TEAEs	1
Total Number of Treatment Related TEAEs	1
Total Number of Not Treatment Related TEAEs	6

Population analysed: The Full Analysis Set (FAS) included all patients who received at least one dose of investigational product. Patients were analysed according to the treatment they were assigned to, irrespective of what treatment they actually received.

Primary outcome: 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

Time frame: Up to 7 days. Mean (Standard Deviation). Unit: ng/mL

Measure	1000mg DS102 (BID) n = 9
Day 0 Unesterified 15(S)-HEPE	542 (399.4)
Day 7 Unesterified 15(S)-HEPE	1060 (1073)
Day 0 Total 15(S)-HEPE	3110 (3721)
Day 7 Total 15(S)-HEPE	4470 (3601)

Adverse events

Time frame: Up to 90 days.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
1000mg DS102 (BID)	4 of 9 (44.4%)	7 of 9 (77.8%)	2 of 9

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mark Thursz principal investigator

Imperial College London

8 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 1000mg DS102 (BID) in people with Severe Acute Decompensated Alcoholic Hepatitis, run by Afimmune at 8 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 29 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, Georgia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and SUSARs. (time frame: Up to 28 days.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03452540.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2022.