Plain English Summary
Background and study aims
HIV (human immunodeficiency virus) is a virus that damages a persons immune system, making them less able to fight infections and disease. There is no cure for the infection , but there are now some very effective treatments, called antiretrovirals, that stop the virus from replicating and therefore help infected people have long and healthy lives. The success of these treatments means that HIV-positive people are now aging. This poses new problems such as heart, kidney, bone and liver diseases which, although associated with ageing, may be more widespread due to the long-term side-effects of anti-HIV drugs. Additionally, drug-drug interactions become increasingly frequent and more complex when treating people who are on treatment for other problems. Therefore, developing new anti-HIV drugs, with less toxicity and likelihood for interactions, is critical. C34-PEG-4-Chol belongs to a family of anti-HIV medications called "fusion inhibitors". C34-PEG-4-Chol is similar to another drug in this family called enfuvirtide. Due to how it is broken down by the body enfurvitide shows little general toxicity and few drug interactions. However it requires injection under the skin twice daily and injection site reactions are common. C34-PEG-4-Chol is expected to need injecting less frequently resulting in fewer reactions. This study will investigate whether giving this drug to humans is safe.
Who can participate?
HIV-positive men, aged between 18-60.
What does the study involve?
Participants are randomly allocated into one of two groups. Those in group 1 are given C34-PEG-4-Chol. Those in group 2 are given a placebo. Samples from each participant are then collected at various time points. Stage 1 involves giving a single dose, allowing researchers to work out the best dose and how often to give it. Stage 2 involves giving 4 doses then checking how much drug gets into the bloodstream and how much the HIV level drops. Each stage should take about 6 months to complete.
What are the possible benefits and risks of participating?
There are no specific advantages of taking part in this study. Risks include side effects to C34-PEG4-Chol which may include injection site reactions (redness, swelling, feeling itchy, bruises, hardened skin or bumps, pain, feeling sore or tender), diarrhoea, nausea / vomiting, raised white blood cell count, pneumonia, feeling weak or tired, headache, feeling dizzy, not being able to sleep, feeling anxious or low in mood, fever, weight loss, poor appetite, pain and feeling numb in hands, feet or legs, swollen glands (lymph nodes). However C34-PEG4-Chol has never been given to humans before so it is possible other unpredictable side effects could occur. As the study involves giving C34-PEG4-Chol without any other anti-HIV drugs, it is possible that HIV resistance to C34-PEG4-Chol could develop. This could also mean that resistance develops to enfuvirtide and any other fusion inhibitor drugs developed in the future. It is possible that if C34-PEG4-Chol were given to a person who was planning to become pregnant with their partner that it might harm an unborn child. Blood tests can sometimes cause bruising and soreness of the arms or, very rarely, a blockage of a vein or a small nerve injury which can cause numbness and pain. Normally these problems disappear with time. Some people may faint while the blood is being drawn.
Where is the study run from?
Imperial College Healthcare NHS Trust (UK)
When is the study starting and how long is it expected to run for?
February 2015 to November 2015
Who is funding the study?
Medical Research Council (UK)
Who is the main contact?
Mrs Nicki Doyle
Trial website
Additional identifiers
EudraCT number
2014-002671-28
ClinicalTrials.gov number
Protocol/serial number
17974
Study information
Scientific title
A phase 1, first in man, study to assess the safety, pharmacokinetic profile and antiretroviral efficacy of C34-PEG-4-Chol, a novel peptide fusion inhibitor for the treatment of HIV-infection.
Acronym
Study hypothesis
The aims of the study are:
1. To assess the safety, pharmacokinetics and pharmacodynamics of C34-PEG4-Chol in HIV-positive individuals.
2. To determine the optimal dose and dosing schedule for C34-PEG4-Chol.
Ethics approval
NRES Committee London - Central, 24/12/2014, ref: 14/LO/2078
Study design
Randomised; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Topic: Infectious diseases and microbiology; Subtopic: Infection (all Subtopics); Disease: Infectious diseases and microbiology
Intervention
1. C34-PEG4-Chol (Peptivir-H), HIV fusion inhibitor
2. Placebo, Sodium chloride 0.9% solution
Intervention type
Drug
Phase
Phase I
Drug names
C34-PEG-4-Chol
Primary outcome measures
1. Safety, pharmacokinetic & pharmacodynamic (viral decay - stage 2 only) parameters; Timepoint(s): Stage 1 - up to day 84 post-single dose
2. Stage 2 - follow up duration to be determined from stage 1
Secondary outcome measures
1. Changes in plasma HIV RNA; Timepoint(s): Stage 1 - measured up to day 28 post-single dose
2. Detailed pharmacokinetic profile of C34-PEG4-Chol when administered at different single doses. Timepoint(s): Stage 1 - profile at day 84 post-single dose
3. Detailed pharmacokinetic profile of C34-PEG4-Chol when administered following multiple dosing; Timepoint(s): Stage 2 - profile at final follow up (duration to be determined from stage 1)
4. Emergence of mutations within heptad repeat-1 (HR-1) region of gp41; Timepoint(s): Stage 2 - measured up to 4th follow up visit (duration of follow up to be determined from stage 1)
5. Listing of all adverse events (grade 1 and above); Timepoint(s): Stage 1-up to day 84 post-single dose
Stage 2-up to final follow up (fu determined from stage 1)
Overall trial start date
23/07/2013
Overall trial end date
01/04/2016
Reason abandoned
Eligibility
Participant inclusion criteria
1. The ability to understand and sign a written informed consent form, prior to participation in any screening procedures, and be willing to comply with all study requirements
2. Male
3. Between 18 to 60 years, inclusive
4. Documented HIV-1 infected for ≥6 months from screening
5. Comorbidities, if present, optimally managed and stable
6. Normal physical examination
7. No clinically significant abnormalities on laboratory screening test
8. BMI 19-28, inclusive
9. Patients who are heterosexually active must agree to use two effective forms of contraception (e.g., condom with spermicide and established hormonal contraception) during heterosexual intercourse, from screening through to completion of the study
10. CD4 count ≥400 cells/µL at screening
11. Plasma HIV RNA ≥10000 copies/mL at screening
12. In the opinion of the investigator not likely to require ART in the next 4 months
13. No clinically significant abnormalities on 12-lead ECG
Participant type
Patient
Age group
Adult
Gender
Male
Target number of participants
Planned Sample Size: 42; UK Sample Size: 42; Description: In stage 1 a maximum of 28 participants (20 active, 8 placebo) will be enrolled.In stage 2 a maximum of 14 participants (11 active, 3 placebo) will be enrolled.
Participant exclusion criteria
1. Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with patient treatment, assessment, or compliance with the protocol. This would include any active clinically significant renal, cardiac, hepatic, pulmonary, vascular, metabolic (thyroid disorders, adrenal disease) disease immunodeficiency disorders, active infection, or malignancy
2. Participation in an investigational trial involving administration of any investigational compound within 90 days of screening
3. History of alcohol use considered by the investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should be expected to remain consistent throughout the study
4. History of recreational drug use within 14 days of screening or a positive drug screen on day of screening
5. Any medication taken listed in Section 8.3 of the protocol (Interaction with other drugs) including over-the-counter medications and herbal products, within 28 days of screening with the exception of vitamins and/or paracetamol. When a concomitant medication is necessary this will be reviewed by the investigator and if not contraindicated may be continued
6. History of drug sensitivity or drug allergy which in the opinion of the investigator may put the patient at increased risk of drug reactions during the study
7. Patients with female partners who are not using 2 effective forms of contraception or with partners who are pregnant
8. Documented resistance of clinical relevance to any other class of HIV antiretroviral drugs
9. Previous exposure to fusion inhibitors (T20/enfuvirtide)
10. Receiving ART within 6 months of screening
Recruitment start date
01/03/2015
Recruitment end date
01/12/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
St Mary's Hospital
Imperial College Healthcare NHS Trust
10th Floor QEQM Building Imperial College
St Mary's Campus
South Wharf Road
London
W2 1NY
United Kingdom
Funders
Funder type
Government
Funder name
Medical Research Council
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
A meeting will be held at the end of the study to provide the results to participants who have taken part in the study. In addition results will be published in peer reviewed scientific journals and presented at conferences at the end of the study.
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary