PET study to assess the distribution of RO7308480 in the brain
| ISRCTN | ISRCTN71330683 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN71330683 |
| EudraCT/CTIS number | 2022-002958-12 |
| IRAS number | 1006931 |
| Secondary identifying numbers | BP43580, IRAS 1006931 |
- Submission date
- 01/12/2022
- Registration date
- 10/02/2023
- Last edited
- 04/12/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Mental and Behavioural Disorders
Plain English summary of protocol
Background and study aims
The study medicine (RO7308480) is an experimental medicine for treating social anxiety disorder. People with social anxiety disorder have intense fear or discomfort in social situations. This can lead to difficulties in relationships, work or school life. Current treatments for social anxiety disorder don’t work well for all patients, or have troublesome side effects.
Studies in animals have shown that by activating sites in the brain called GABAA receptors, animals had a decrease in anxiety-like behaviours. We hope RO7308480 will reduce the symptoms of social anxiety disorder by attaching to these sites.
We’ll test single doses of RO7308480 in healthy volunteers to find out its blood levels, side effects, and to measure how much RO7308480 binds to GABAA receptors. To find out, we’ll use a brain scan called a PET (positron emission tomography) scan, which makes images of the brain.
Who can participate?
Healthy volunteers aged 23 – 55 years
What does the study involve?
The study is in 2 parts. Part 1 will have up to 5 groups of up to 3 participants and Part 2 will have up to 3 groups of up to 3 participants. Participants will have 2 study sessions. Eligible participants (up to 24 healthy men and women, aged 23–55 years) will take a single dose of RO7308480 by mouth. Participants will have 3 PET scans, and an MRI (magnetic resonance imaging) scan at a separate screening visit. The MRI uses a strong magnetic field to take pictures of the brain.
Participants will take up to 7 weeks to finish the study. They’ll make 3 outpatient visits, and have 2 study sessions. They’ll stay on the ward for 1 night in Session 1, and for 3 nights in Session 2.
What are the possible benefits and risks of participating?
Benefits:
Participants will not have any benefit from participating in the study.
Risks:
The study is divided into 2 parts (called Parts 1 and 2). Doses from 1mg up to 25mg of RO7308480 will be tested in Part 1.
Like other medicines that enter the brain, the study medicine could affect participants’ mood and behaviour, but we haven’t seen those side effects in animal studies. Some medicines that enter the brain may increase the risk of people taking their own life, so we’ll ask participants often if they’ve had any such thoughts, or if they’ve ever tried to take their own life.
Participants will have 3 PET scans, using either [11C]RO7285378 or [11C]flumazenil as a radioactive tracer. To date, over 500 people worldwide have been given [11C]flumazenil. [11C] RO7285278 is a new tracer. So far, it has been tested in 18 healthy volunteers and no side effects were reported. The proposed doses of PET ligands to be administered have been optimised to provide the lowest radiation exposure while maintaining an adequate quality of the data acquired.
In this study, we'll monitor the participants closely, and we won't increase the dose of RO7304840 unless the previous dose causes no important side effects. If a participant is withdrawn, we ask them to consent to a final follow up. We document their consent using an information and consent form (ICF), which has been approved by the HRA’s Generic Review Committee (GRC; REC ref: 18/GR/0054).
During their stay, participants must follow HMR’s ‘house rules’. Our information leaflet is given to volunteers at screening and has been approved by the GRC (REC ref: 18/GR/0104).
If a participant, or their partner, becomes pregnant during the study, we ask to contact their GP about the pregnancy – we document that using a generic ICF that has been approved by the HRA’ s GRC (REC ref: 18/GR/0055 or 21/GR/16).
If we find any medically important problem at screening, our physician will tell the participant in person, and pass on the results to the participant’s GP, using a letter template, which has been approved by the GRC (REC ref: 18/GR/0101).
We contact participants’ GPs to inform them that their patient has volunteered to take part in a study, and provide the GP with a study summary. Our GP letter templates have been approved by the GRC (REC refs: 18/GR/0098 and 18/GR/0099); therefore, we’ve not attached copies of those letters to this application. Participants give consent for us to contact their GP when they sign the ICF.
Where is the study run from?
HMR London (UK)
When is the study starting and how long is it expected to run for?
November 2022 to June 2024
Who is funding the study?
F. Hoffmann-La Roche Ltd (Switzerland)
Who is the main contact?
global.trial_information@roche.com
Contact information
Scientific
Building 1
Grenzacherstrasse 124
Basel
CH-4070
Switzerland
| Phone | +41 616878333 |
|---|---|
| global.trial_information@roche.com |
Principal Investigator
Cumberland Avenue
London
NW10 7EW
United Kingdom
| Phone | +44 20 8961 4130 |
|---|---|
| tyamamoto1@hmrlondon.com |
Study information
| Study design | Interventional non randomized |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Pharmaceutical testing facility |
| Study type | Other |
| Scientific title | A phase I non-randomized, open label, adaptive, parallel group, human positron emission tomography (PET) study to assess the occupancy of brain γ1 and γ2 containing GABAA receptors of RO7308480 using [11C]RO7285378 and [11C]flumazenil following single oral doses in healthy participants. |
| Study objectives | Current study hypothesis as of 27/06/2023: Primary objectives: Part 1 - To assess the relationship between RO7308480 plasma concentration and brain occupancy of GABAA receptor subtypes (containing the γ1 subunit) after selected single oral doses of RO7308480 using [11C]RO7285378 PET tracer *Part 2 - To assess the relationship between RO7308480 plasma concentration and brain occupancy of GABAA receptor subtypes (containing the γ2 subunit) after selected single oral doses of RO7308480 using [11C]flumazenil PET tracer Secondary objective: To find out if single doses of RO7308480 have any important side effects in healthy participants when taken by mouth. _____ Previous study hypothesis: Primary objectives: *Part 1 - To find out if RO7308480 enters the brain and binds specifically to a site called GABAA γ1 subunit-containing receptors after a single oral dose. *Part 2 - To find out if RO7308480 can bind to a site in the brain called a GABAA γ2 subunit-containing receptors after a single oral dose. Secondary objective: To find out if single doses of RO7308480 have any important side effects in healthy participants when taken by mouth. |
| Ethics approval(s) | Approved 07/02/2023, London - Chelsea (Level 3, Block B, Whitefriars, Lewins Mead, Bristol, BS1 2NT, UK; +44 207 104 8356; chelsea.rec@hra.nhs.uk), ref: 22/LO/0876 |
| Health condition(s) or problem(s) studied | Social anxiety disorder |
| Intervention | Participants will receive a single dose of RO7308480 capsule, orally on Day 1. Multiple dose levels of RO7308480 will be tested in Part 1 and Part 2 of the study. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | RO7308480 |
| Primary outcome measure | 1. Pharmacodynamic (PD): Occupancy of brain GABAA γ1 and GABAA γ2 subunit containing receptors by RO7308480 measured using 1 baseline and 2 post-dose PET scans to assess GABAA receptor occupancy. The baseline PET scan will be carried out on Day -7 or predose on Day 1. The second and third PET scans will be approximately 1.5-2.5 hours and 24-36 hours post-dose. The timing of the on-treatment PET scans may or may not be adjusted after the review of the results from the previous groups. 2. Pharmacokinetic (PK): RO7308480 plasma concentrations measured using blood samples for plasma concentration of RO7308480 will be taken before and after each on-treatment PET scan. |
| Secondary outcome measures | Safety and tolerability of single oral doses of RO7308480, as judged by adverse events, vital signs, physical, and neurological exams, ECG parameters, clinical laboratory results, and C-SSRS. Vital signs, medical examination (including weight), laboratory safety tests, ECGs and adverse events will be assessed frequently until the subject's final visit, 10-14 days after their dose of RO7308480. Serious adverse events (SAEs) will be assessed up to 2 weeks after the last dose of RO7308480. If the Investigator learns of an SAE at any time after the follow up period that they considered reasonably related to study treatment or study participation, the Investigator will notify the Sponsor. |
| Overall study start date | 28/11/2022 |
| Completion date | 27/06/2024 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 23 Years |
| Upper age limit | 55 Years |
| Sex | Both |
| Target number of participants | 24 |
| Key inclusion criteria | 1. Participants aged 23- 55 years 2. Body mass index 18-32 kg/m² 3. In good health, as judged by medical history, medical examination, vital signs, ECG and clinical laboratory tests 4. Able to communicate with study personnel 5. Reliable, willing, and likely to comply with the protocol 6. Willing to comply with the contraception requirements of the protocol 7. Consent to inform their GP of their participation in the study, and to enter their details into the over-volunteering database (TOPS). |
| Key exclusion criteria | 1. Not healthy (clinically significant abnormality in our screening tests, which include ECG, vital signs, physical examination, MRI scan and laboratory safety tests of blood and urine); 2. Abuse of alcohol or drugs; 3. Serious reaction to any medicine; 4. Taken certain medicines (ones that could affect the breakdown of the study medicine or that affect the central nervous system or blood flow) during the 30 days before dosing; taken any medicine (except paracetamol), herbal remedies or dietary supplements during the 2 weeks before dosing; taken isotretinoin 2 years prior to screening; 5. History of ophthalmologic conditions that might affect the corneal surface (such as keratoconus, severe dry eye disease and/or corneal dystrophy); wear prescription contact lenses on a daily basis, unless they are not willing to switch to prescription glasses during the study, including the follow-up visit; 6. Have had any condition or operation that might affect the way the body absorbs medicines; have had any clinically significant disease; history of seizures or convulsion ‘fits’ (other than single benign febrile convulsion of childhood); 7. Objection by GP on medical grounds — because they might increase the risk, or confound the assessment of receptor occupancy 8. Tried to commit suicide or homicide, had suicidal or homicidal thoughts; mental illness might compromise consent; 9. Pregnant or breastfeeding; unwilling to comply with the contraception requirements of the protocol — because of the potential risk to the unborn or breastfed baby; 10. Claustrophobia; any condition which would make it difficult to lie still for very long; 11. Metal in the body (eg pacemaker, mechanical heart valve, replacement hip joint, shrapnel); have worked as a metal worker, machinist or welder — due to increased risk from MRI scans 12. Exposure to ionising radiation as part of a research study, such that combined with the exposure from this study their effective dose in a 12 month period would exceed 10 mSv. 13. Unsatisfactory venous access or contraindication for arterial cannulation; 14. Participants who have donated 500 mL of blood or blood products or had significant blood loss within 3 months prior to screening. 15. participants who use 5 or more cigarettes per day or equivalent amount of tobacco or nicotine products — because participants must be able comfortably to abstain from smoking during the study. 16. Alanine aminotransferase and total bilirubin above the upper limit of normal (ULN) (added 27/06/2023) Criteria are designed to select healthy young participants, who are robust enough to recover quickly from any adverse effects of RO7308480. |
| Date of first enrolment | 15/02/2023 |
| Date of final enrolment | 11/06/2024 |
Locations
Countries of recruitment
- United Kingdom
Study participating centre
London
NW10 7EW
United Kingdom
Sponsor information
Industry
Grenzacherstrasse 124
Basel
4058
Switzerland
| Phone | +41 616878333 |
|---|---|
| global.trial_information@roche.com |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 02/02/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Peer reviewed scientific journals Internal report Conference presentation Publication on website Submission to regulatory authorities |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to participant-level data not being a regulatory requirement |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
04/12/2023: The following changes were made to the trial record:
1. The contact email and telephone number were changed.
2. The sponsor email and telephone number were changed.
3. The plain English summary was updated to reflect these changes.
30/06/2023: The EudraCT/CTIS number was updated.
27/06/2023: The following changes were made to the trial record:
1. The principal investigator contact was changed.
2. The study hypothesis was changed.
01/12/2022: Trial's existence confirmed by NHS HRA.
