Phase 1 Study of ABI-H2158 in patients with Chronic Hep B infection

• Research type

  Research Study

• Full title

  A Phase 1 Study of the Safety, Tolerability, Pharmacokinetics, and Food Effect of Single and Multiple Doses of ABI-H2158 in Healthy Volunteers; and the Multiple-Ascending Dose Pharmacokinetics and Pharmacodynamics in Patients with Chronic Hepatitis B Infection

• IRAS ID

  260896

• Contact name

  Kaushik Agarwal

• Contact email

  kosh.agarwal@nhs.net

• Sponsor organisation

  Assembly Biosciences, Inc

• Eudract number

  2019-000100-15

• Clinicaltrials.gov Identifier

  NCT03714152

• Duration of Study in the UK

  0 years, 3 months, 0 days

• Research summary

  Research Summary
  This is a Phase I, first-in-human and first in patients study with ABI-H2158 for patients with chronic Hepatitis B (CHB). The study will look at the safety, tolerability and PK and PD following dosing with the ABI-H2158. PK refers to how the study drug is absorbed (taken up into the body), metabolised (chemically broken down), distributed through the body, and excreted (removed from the body). PD refers to assessing the effects of the study drug and the way in which the study drug works (mechanism of action), by measuring specific biomarkers in blood and evaluating changes in viral load.
  There will be 3 parts to the study: Part 1 will include healthy volunteers who will receive a single dose of ABI-H2158 with and without food. Part 2 will include healthy volunteers who will receive daily doses of ABI-H2158 for 10 days. When a safe dose is confirmed, Part 3 of the study will treat patients with CHB. Part 3 will explore relationship between dose and anti-viral potency in patients with CHB.
  The UK site will only participate in Part 3 of the study. Participants with CHB will be asked to take ABI-H2158 or placebo for 14 consecutive days. There will be 3 cohorts of 9 participants (there is an option to include up to 6 cohorts). In each cohort 7 participants will receive ABI-H2158 and 2 will receive a matching placebo (dummy drug). The dose may be increased after each cohort following a review of safety, tolerability and available PK and antiviral efficacy data from a minimum of 14 days of study drug administration in at least 7 CHB participants in a given cohort. As this is a blinded study, the participants and clinical team will not know which treatment they are receiving.

  Summary of Results
  A phase 1 study of ABI-H2158 in patients with chronic hepatitis B infection.
  (Full title: A phase 1 study of the safety, tolerability, pharmacokinetics, and food effect of single and multiple doses of ABI-H2158 in healthy volunteers; and the multiple ascending dose pharmacokinetics and pharmacodynamics in patients with chronic hepatitis B infection.) Protocol number: ABI-H2158 EudraCT number: 2019-000100-15 ClinicalTrials.gov Identifier: NCT03714152

  2. Who sponsored the study?
  Assembly Biosciences, Inc.
  331 Oyster Point Boulevard, 4th Floor
  South San Francisco, CA 94080, USA

  3. General information about the clinical study A total of 56 healthy volunteers and 37 people with chronic hepatitis B infection were enrolled on the study. The study took place in the following countries:
  • New Zealand - Parts 1, 2 and 3 (59 subjects)
  • China – Part 3 only (12 subjects)
  • Hong Kong – Part 3 only (10 subjects)
  • South Korea – Part 3 only (5 subjects)
  • United Kingdom – Part 3 only (5 subjects)
  • United States – Part 3 only (2 subjects)
  The study started in November 2018 and ended in November 2020.
  In this study, researchers looked at how this drug works in the human body. It consisted of three parts.
  • Part 1 – healthy volunteers were given single doses of study drug at increasing dose levels
  • Part 2 – healthy volunteers were given multiple doses of study drug at increasing dose levels
  • Part 3 – people with chronic hepatitis B infection were given multiple doses of study drug at increasing dose levels
  Researchers did medical tests on men and women before and after they took the drug. The researchers wanted to know if there were:
  • Any unwanted side effects of the drug
  • Any chemical changes in blood or urine, and
  • Whether the drug helped to reduce the amount of hepatitis B virus in the body (Part 3 only)
  During each of the three parts of the study, some participants received placebo treatment instead of study drug. This treatment looked the same as the study drug but did not include any of the active ingredient. The participants were put into the groups either receiving study drug or placebo by chance (randomised) to reduce differences between the groups. Putting people into groups by chance helps to make the different groups equal and therefore makes the comparison between the groups fairer. This study was also “double-blinded”. This means that neither the participants nor the doctors knew who was given which treatment. This was done to make sure that the trial results were not influenced in any way.

  4. Who was included in the study?
  This study included both male and female healthy volunteers (Parts 1 and 2) and people with chronic hepatitis B infection (Part 3). Healthy volunteers could be between 18 and 55 years of age and people with chronic hepatitis B infection could be between 18 and 65 years of age. All participants were required to have a Body Mass Index (BMI) of less than or equal to 34 kg/m2 at the time of screening.
  In Parts 1 and 2 participants were predominately male, white, and not of Hispanic or Latino ethnicity. In Part 3, there was a roughly equal number of male and female participants and the majority were Asian and not of Hispanic or Latino ethnicity.

  5. Which drugs were studied?
  The drug being investigated in this study was ABI-H2158, which is being developed as a potential treatment for patients with chronic hepatitis B infection. The study drug was presented as two strength oral tablets, containing 5 mg or 25 mg of ABI-H2158 or matching placebo.
  In Part 1 healthy volunteers received oral doses of either 5 mg, 25 mg, 100 mg, 300 mg, 500 mg ABI-H2158 or matching placebo having fasted for at least 10 hours prior to dosing. An additional cohort of participants in Part 1 received 100 mg ABI-H2158 or matching placebo following a high-fat meal.
  In Part 2 healthy volunteers received oral doses of either 300 mg ABI-H2158 once daily or twice daily or matching placebo in the fasted state for 10 days.
  In Part 3 people with chronic hepatitis B infection received oral doses of ABI-H2158 at either 100 mg, 300 mg once or twice daily, or 500 mg once daily or received matching placebo for 14 days. The doses in Part 3 were given without regard to food (i.e., in either fed or fasted state).
  Please refer to Section 3 ‘General information about the clinical study’ regarding allocation of participants to study drug or placebo.

  6. What were the side effects?
  Side effects are unwanted medical events (such as a headache) that happen during the study and are reported because the study doctor (investigator) believes the events were related to the treatments in the trial. Not all the people in this study had side effects.
  There were no deaths, serious or other significant medical events reported during this study. There was a total of 27 events reported that were considered to be related to the study treatments. The most common side effects were headache, dizziness and increases in liver enzymes (ALT and AST) (Part 3 only). Most events were mild and resolved. No one was withdrawn from the study due to any side effects.

  7. What were the overall results of the study?
  This study was conducted and completed as planned.
  ABI-H2158 was found to be generally safe and well tolerated in single doses up to 500 mg and multiple doses up to 300 mg twice daily for 10 days in healthy volunteers. This drug was also found to be generally safe and well tolerated at dose levels up to 500 mg once daily for 14 days in people with chronic hepatitis B infection.
  Following 14 days of dosing, ABI-H2158 was found to reduce the amount of hepatitis B virus in the body, as measured by the levels of hepatitis B virus genetic material (DNA and pgRNA) in the blood.

  8. How has this study helped patients and researchers?
  Researchers look at the results of many studies to understand which drugs work and how they work. It takes lots of people in many studies all around the world to advance medical science. This summary only shows the results from this one study. Other studies may find different results.
  This was a first time in man study of ABI-H2158, conducted in healthy volunteers and a small number of people with chronic hepatitis B infection. The findings from this study will be used in other larger studies to learn whether people with chronic hepatitis B infection are helped by this drug.

  9. Are there plans for further studies
  No further clinical studies with ABI-H2158 are planned at the current time.

  10. Where can I find more information about this study?
  To learn more about this study, you can find more detailed information on this website: https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbRehJ-2Fi4xyo44sEgJVCl5BcbW9wgc64X2JjNxW-2BqMpAMVdg6Mwe3V2NXGqPtR4X96A-3D-3DZafo_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YIFRkOiLgzNIF3jzp-2FGAUf8MgkYXNuzqfAqigLoGjjW2LFX-2FWU8sYqjymPHFnIHiO4wUABY-2FLhIWq4GoNFuU0LRe7wdzXOhfthqXLqPBcYhkE4z-2Bmq6pbsLcfp2yZSrggDnjZXcGZmxlI20affkJ7OvbXLDfs9Mvfh63fzf08DnkA-3D-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7Caee7018cec604712819008d9e652e096%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637794065891622805%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=bZGNJpa9Rn9cCMeM15uXIwYLh3h%2B3e0G5Jxw5xP2dew%3D&reserved=0

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• REC name

  London - Chelsea Research Ethics Committee

• REC reference

  19/LO/0507

• Date of REC Opinion

  23 May 2019

• REC opinion

  Further Information Favourable Opinion