Phase 2a study of antiviral activity of CC-42344 in a human viral challenge model in healthy adults
Research type
Research Study
Full title
A Randomised, Phase 2a, Double-blind, Placebo-controlled Study to Evaluate the Antiviral Activity Against Influenza Infection, Safety, Tolerability, and Pharmacokinetics of CC-42344 Via a Human Viral Challenge Model in Healthy Participants.
IRAS ID
1007765
Contact name
Sam Lee
Contact email
Sponsor organisation
Cocrystal Pharma Inc.
Clinicaltrials.gov Identifier
NCT0616053
Research summary
The purpose of this research is to test the effects of an experimental drug called CC-42344 and that it may be useful in treating infection with the influenza virus. Influenza virus causes an infectious disease commonly referred to as ‘the flu’. The Influenza virus can spread easily through the air, often by coughs and sneezes. The disease is often mild in healthy adults but can cause more severe symptoms in pregnant women, elderly people, people with a compromised immune system & those with chronic conditions like diabetes, asthma or heart failure. CC-42344 works by stopping the growth & spread of the influenza virus in the body. The approved treatments for the flu are drugs called zanamivir and oseltamivir, but new drugs are needed because flu virus may be becoming ‘resistant’ to these drugs. There remains a need to develop drugs with high effectiveness for providing longer & broader protection. Up to 96 healthy adult volunteers, aged 18-55 will be invited to participate in this research study with a minimum of 26 per group. The study consists of 3 stages: Screening, Quarantine & Follow-up. The study will consist of 3 groups. Following an initial first dose, Group 1 will be assigned the study drug twice a day for 5 days in total and Group 2 will be assigned the study drug in the morning and the placebo in the evening from D1 to D5. Group 3 will be assigned to the placebo and will receive this in the morning and evening from D1 to D5.
Subjects will be randomly assigned to receive placebo and/or the study drug as an oral capsule. The participants will enter quarantine on day -2/-1 and will be dosed with CC-42344 or placebo between Day 1 & Day 5. On Day 0 the participants will be inoculated with the influenza virus. After completion of the Quarantine phase, participants will need to return to the clinic approximately 20 days after for a follow-up visit (D28) to undergo tests.
The expected duration of study participation for a participant is approximately 4 months.Summary of study results:
1 STUDY NAME
This was a Phase 2a study of anti-viral activity of CC-42344 in a human influenza challenge
model in healthy adult volunteers.
1.1 Study name
A Randomised, Phase 2a, Double-blind, Placebo-controlled Study to Evaluate the Antiviral
Activity Against Influenza Infection, Safety, Tolerability, and Pharmacokinetics of CC-42344 Via a Human Viral Challenge Model in Healthy Participants.
1.2 Protocol number
Cocrystal Protocol Number: CC-42344-P2-001. hVIVO Protocol Number: CPI-CST-001.
1.3 Other trial identifiers
Clinicaltrials.gov number: 06160531
1.4 Abstract
Purpose of the study: To see if a medicine called CC-42344 is useful in treating influenza, commonly known as “flu”.
What was tested: The medicine tested was CC-42344 at two dose levels, low and high,
compared with placebo (an identical looking treatment but with no medicine in it), in a Phase 2 trial in healthy volunteers.
People taking part in this trial: 78 healthy adults, aged between 18 and 55 years, took part at one site in London, UK.
Topline results: The study was inconclusive in terms of the antiviral (anti-flu) activity of CC-42344.
Safety: Twenty-five participants experienced adverse events that were generally considered unrelated to the test drug. None of the participants discontinued the study because of adverse events, and none of the events was severe or serious.
2 WHO SPONSORED THIS STUDY?
Cocrystal Pharma Inc. sponsored the study.
3 GENERAL INFORMATION ABOUT THE CLINICAL TRIAL
3.1 Where was the study done?
The study was done in London, UK. It was conducted by hVIVO plc, formerly at Queen Mary
BioEnterprises Innovation Centre, 42 New Road, London, E1 2AX and now at 40 Bank Street, Floor 24, London E14 5NR.
3.2 When was this study done?
The study started in November 2023 (first participant, first visit) and finished in May 2024 (last participant, last visit).
3.3 What was the main objective of this study?
In this study, researchers looked at whether CC-42344 reduced the effects of the flu virus compared with placebo. Researchers did medical tests on the study participants before and after
they were given flu and received the study drug. The trial did not test if the drug helps toimprove health. Healthy volunteers took part in this study and were put into one of three groups by chance: low and high dose CC-42344 and placebo. The trial was double-blinded, meaning
that neither the participants nor the researchers knew who was given which treatment.
4 WHAT PATIENTS/PEOPLE WERE INCLUDED IN THIS STUDY?
4.1 Number of subjects included in the trial by country
This trial included 78 healthy volunteers from the UK.
4.2 Age group and gender breakdown
In total, 30 females and 48 males took part in this study. Participants ranged in ages from 23 to 53 years.
4.3 Inclusion and exclusion criteria
This study enrolled healthy adult male or female participants aged between 18 and 55 years old, with a body weight ≥50 kg and body mass index (BMI) ≥18 kg/m2 and ≤35 kg/m2. During the
screening period, tests were done to check if subjects were already immune to the influenza challenge virus.
5 WHICH MEDICINES [OR VACCINES] WERE STUDIED?
CC-42344 (the trial medicine) and matching placebo were used in this study. Seventy-eight participants were randomised (allocated by chance) to one of three groups, with an equal number (26) in each group. The study treatments were given by mouth in identical capsules to ensure the study was double-blind.
High dose CC-42344: Day 1 – 800 mg am and 400 mg pm. Days 2 to 5 – 400 mg am and pm
Low dose CC-42344: Day 1 – 800 mg am and Placebo pm. Days 2 to 5 – 400 mg am and
Placebo pm
Placebo: Day 1 Placebo am and pm. Days 2-5 Placebo am and pm
6 WHAT WERE THE SIDE EFFECTS?
Adverse reactions or side effects are unwanted medical events (such as a headache) that happen during the study, and are reported because the trial doctor believes the side effects were related
to the treatments in the trial. Not all the people in this trial had side effects.
There were 40 adverse events in this study but only 11 were considered adverse reactions or
side effects. The trial doctor considered whether the side effects were related to the flu challenge or to the test medication, CC-42344.
Side effects in the CC-42344 high dose group included six related to the flu challenge but none related to CC-42344. The flu challenge side effects were mild except for one case of high Creactive protein which was moderate. All side effects resolved within 4 days or less.
Side effects in the CC-42344 low dose group included two in one participant related to the test drug. These were mild diarrhoea and dizziness which lasted for 4 days. In this group there were also three cases of mild flu challenge side effects which resolved within 3 days or less. There were no side effects in the Placebo group.
None of the adverse events led to participants discontinuing the study. There were no severe or serious adverse events.
7 WHAT WERE THE OVERALL RESULTS OF THE STUDY?
The antiviral activity of CC-442344 was not demonstrated in this study of healthy volunteers who were inoculated with flu and then given treatment with CC-42344.
In the high-dose group, 26 subjects received 5 days treatment with CC-42344 after administration of the flu virus. There were no side effects related to the test drug.
In the low-dose group, 26 subjects received 5 days treatment with CC-42344. There were two side effects in one subject which included mild, short-lived diarrhoea and dizziness.
In the placebo group, 26 subjects received 5 days treatment with a dummy treatment, identical to CC-42344. There were no side effects related to placebo.
The trial completed as planned.
8 HOW HAS THIS STUDY HELPED PATIENTS AND RESEARCHERS?
The results only apply to the treatment of healthy volunteers aged 18-55 years. This increases the number of people who have received the test drug CC-42344 and supports previous findings of a well tolerated treatment.
The study was not intended to show the effect of treatment in a population suffering flu.
There were 2 important limitations to the study. One was related to the number of volunteers infected with flu after receipt of the virus, which was only 31/78 (40%). The second limitation related to pre-existing immunity to this type of flu. Just before the study,
58/78 (74%) of volunteers had antibodies to the type of flu which was used to infect them which contributed to the low rate of infection.
Other trials in the future may show something different.
The trial has completed. Findings will be used alongside lessons that have been learned to design another study. Cocrystal Pharma want to see if people are helped by this drug.
9 ARE THERE PLANS FOR FURTHER STUDIES?
Further clinical trials with Drug CC-42344 are planned.
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://clinicaltrials.gov/study/NCT06160531REC name
South Central - Hampshire B Research Ethics Committee
REC reference
23/SC/0183
Date of REC Opinion
8 Sep 2023
REC opinion
Further Information Favourable Opinion