Phase 2a study of the prophylactic antiviral activity of CD388 in an influenza challenge model
Research type
Research Study
Full title
A proof-of-concept, randomised, double-blind, placebo-controlled, phase 2a study to assess the prophylactic antiviral activity against influenza, safety, tolerability, and pharmacokinetics of cd388 via a human viral challenge model
IRAS ID
1005986
Contact name
Joaquin Sosa
Contact email
Sponsor organisation
Cidara Therapeutics, Inc.
ISRCTN Number
ISRCTN14841526
Clinicaltrials.gov Identifier
Research summary
Summary of Research
The purpose of this research is to test the effects of an experimental drug called CD388 that may be useful in preventing infection in people infected 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 children and most healthy people but can be severe in pregnant women, people older than 65yr, people whose immune system is down and people with chronic conditions like diabetes, asthma or heart failure. CD388 works by stopping the growth and 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 the flu virus may be becoming ‘resistant’ to these drugs. Up to 168 participants , healthy adults aged, 18-55 will be invited to participate in this research study. The study will consist of 3 stages: Screening, Quarantine and Follow-Up. The study will consist of 2 Groups, which will be subdivided into smaller groups. Participants in each subgroup will receive different dose levels of CD388 or placebo but will not exceed the maximum study doses of 150 mg. The subjects who are randomly assigned to receive placebo will receive an injection under the skin in the same volume as the study drug. The participants will enter quarantine on day -6 and will be dosed with CD388 or placebo between Day -6 and Day -2. 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 5 times on Day 17, Day 28, Day 60, Day 120 and Day 180 to undergo tests.Summary of Results
This study involved 59 people who participated in a clinical trial from 09Sep2022 to 17Jul2023 at hVIVO Services Limited in UK.
At random, the participants were divided into 3 different groups. One group (2 participants) received a low dose (50 mg) of a new medication being tested called CD388. Another group (28 participants) received a high dose (150 mg) of CD388. The last group (29 participants) received a placebo (a fake medicine with no active ingredients). Except for 1 participant in the placebo group, everyone was given the influenza virus to challenge (or test) against CD388. All participants completed the study, except for 2 participants in the placebo group. One participant decided not to continue the study for personal reasons, and one participant was lost to follow up as they were unable to be contacted.
There were no major differences observed in the three groups in the following categories: sex, age, ethnicity, race, or BMI (measure of weight in comparison to height). 62.7% of participants were males. The average age of participants was 33 years and average BMI was 25.83 kg/m2. All participants were of non-Hispanic/Latino origin.
Overall, participants in the high-dose group reported more side effects (unintended responses) after receiving the study medication than in the placebo group. Specifically, 41 participants reported a total of 63 side effects after CD388 was given whereas19 placebo group participants reported 25 side effects. 1 low-dose group participant reported 4 side effects, and 21 high-dose group participants reported 34 side effects.
One high-dose group participant reported injection site pain after CD388 was given.
Overall, the most reported side effects after CD388 was given were upper respiratory tract infection by 26 participants, 6 participants reported headaches, and 4 showed an increase of aspartate aminotransferase (an enzyme mostly found in the liver, but also in muscles and other organs in the body, which increases when cells are damaged). All side effects reported after CD388 was given were considered not to be related to CD388 and either not related to or unlikely to be related to the influenza challenge virus. No side effects led to participants leaving the study and no serious side effects or deaths were reported. All side effects were reported as recovered/resolved, except for 1 side effect of a tympanic membrane perforation (tear in the eardrum) in the high-dose group, which was reported as present, but stable, at the end of the study.
Most side effects reported after CD388 was given were mild in severity, except for 4 side effects of moderate severity in the high-dose group, which were reported in 3 participants with aspartate aminotransferase increase and abnormal heart readings on an EKG (a test to check the electrical activity in the heart). Two participants in the placebo group had or reported moderately severe side effects: an upper respiratory tract infection and increased aspartate aminotransferase.
Efficacy:
The study showed that the high-dose group participants had a lower viral load (amount of virus in an infected person) after receiving the influenza virus compared to the placebo group participants, although the finding was not very strong.
The peak viral load (highest amount of virus in an infected person at the time) was significantly reduced in the high-dose group as compared to the placebo group. However, the difference of reduction of the amount of virus in the infected participants of the high-dose group compared to the placebo group was not very strong.
Overall, the number of infected participants as determined by a laboratory test, was lower than expected. Fewer participants in the high-dose group developed positive infection as determined by laboratory test (21.4%) compared to the placebo group (50%).
The high dose of CD388 seemed to lower the number of people who actually got the flu compared to the placebo group. This was a strong finding. Although the participants in the high dose CD388 group had fewer virus particles and cleared the virus earlier than the participants who received placebo group participants, the differences between the two group of participants were not strong.
Summary:
The study looked closely at the overall health of the participants. This included checking blood tests, vitals, heart test (EKG), physical exams, lung function tests and immune test against CD388. Reassuringly, no major changes were seen in any group. There was just one minor abnormality noted on an EKG in the high-dose drug group and one minor physical exam abnormality in the placebo group.
Moving to the effectiveness of CD388, the analysis of the data showed some promise for the high dose of CD388. It seemed to reduce the chance of getting the flu disease and the amount of flu virus in peoples’ noses was lower compared to what was expected. Other tests done in the study also showed some improvement, suggesting a potential benefit.REC name
Wales REC 2
REC reference
22/WA/0191
Date of REC Opinion
2 Aug 2022
REC opinion
Further Information Favourable Opinion