A study in healthy volunteers to investigate the safety and tolerability of a new test medicine (DES-9384)
| ISRCTN | ISRCTN85847953 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN85847953 |
| Integrated Research Application System (IRAS) | 1007622 |
| CRO study code | QSC300414 |
| Sponsor | D. E. Shaw Research |
| Funder | D. E. Shaw Research |
- Submission date
- 05/05/2023
- Registration date
- 09/05/2023
- Last edited
- 20/08/2026
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English summary of protocol
Background and study aims
The Sponsor is developing the test medicine, DES-9384, for the potential treatment of rheumatoid arthritis. Rheumatoid arthritis is an autoimmune disease which occurs when the immune system attacks the cells which line the joints by mistake, making the joints swollen, stiff and painful. Over time the joints, cartilage and nearby bone can become damaged. The condition usually affects the hands, feet and wrists.
Who can participate?
Healthy male and non-pregnant, non-lactating female volunteers aged between 18 and 55 years.
What does the study involve?
In Part 1, up to 56 volunteers will be split into seven cohorts. Each cohort will receive two oral doses of the test medicine at different dose levels, or placebo, 12 hours apart and in the fasted state. Following a minimum 7-day washout period Cohort 4 only will take part in Period 2, where volunteers will receive 2 oral doses of the test medicine, or placebo, 12 hours apart in the fed state. Volunteers will be discharged 48 hours post morning dose in each study period and will return for a follow-up visit 3-5 days after discharge.
In Part 2, up to 48 volunteers will be split into four cohorts. Based on Part 1 results, each cohort will receive either one or two oral doses a day of the test medicine, or placebo, for 7 consecutive days, in the fasted state. Volunteers will be discharged 48 hours post final dose and will return for a follow-up visit 3-5 days after discharge.
Volunteer’s blood and urine will be taken throughout the study for analysis of the test medicine and for their safety.
Volunteers are expected to be involved in this study for approximately 6 weeks from screening to the follow-up visit for all cohorts in Part 1 except Cohort 4, who are expected to be involved for 7 weeks, and approximately 6 weeks for volunteers in Part 2.
What are the possible risks and benefits of participating?
Healthy volunteers will get no medical benefit from the test medicine; however, the aims of the study can be most efficiently met in volunteers with no concurrent medical conditions and who do not need to take concomitant medication that might interfere with the study objectives or increase the risk of the study. The risk/benefit evaluation in this study supports the use of healthy volunteers.
Where is the study run from?
Quotient Sciences Limited (United Kingdom)
When is the study starting and how long is it expected to run for?
July 2023 to February 2024
Who is funding the study?
D. E. Shaw Research, LLC (USA)
Who is the main contact?
recruitment@weneedyou.co.uk
Contact information
Principal investigator
Quotient Sciences Limited
Mere Way
Ruddington Fields
Ruddington
Nottingham
NG11 6JS
United Kingdom
| Phone | +44 (0)330 303 1000 |
|---|---|
| Recruitment@weneedyou.co.uk |
Scientific
120 West 45th Street
39th Floor
New York
NY 10036
United States of America
| Phone | +1 (0) 212 849 0880 |
|---|---|
| Fabrizio.Giordanetto@DEShawResearch.com |
Public
120 West 45th Street
39th Floor
New York
NY 10036
United States of America
| Phone | +1 (0) 212 849 0880 |
|---|---|
| Fabrizio.Giordanetto@DEShawResearch.com |
Study information
| Primary study design | Interventional |
|---|---|
| Allocation | Randomized controlled trial |
| Masking | Blinded (masking used) |
| Control | Placebo |
| Assignment | Parallel |
| Purpose | Phase I study in healthy volunteers |
| Scientific title | A two-part first-in-human study to assess the safety, tolerability, pharmacokinetics and pharmacodynamic effects of single and multiple ascending oral doses of DES-9384 in healthy male and female subjects |
| Study objectives | The trial will meet the following primary and secondary objectives: Primary objectives 1. To assess the safety and tolerability of single twice daily (BID) (Part 1) and multiple once daily (QD) or BID (Part 2) ascending doses of DES-9384 administered as an oral capsule to healthy male and female subjects Secondary objectives 1. To characterise the PK following single BID (Part 1) and multiple QD or BID (Part 2) ascending oral doses of DES-9384 administered as a capsule 2. To assess the effect of food (Part 1) on the PK of a capsule formulation of DES-9384 |
| Ethics approval(s) |
1. Approved 15/05/2023, Health and Social Care Research Ethics Committee B (Office for Research Ethics Committees in Northern Ireland (ORECNI), Lissue Industrial Estate West, 5 Rathdown Walk, Lisburn, BT28 2RF, United Kingdom; -; RECB@hscni.net), ref: 23/NI/0043 2. Approved 15/05/2023, MHRA (10 South Colonnade, Canary Wharf, London, E14 4PU, United Kingdom; +44 (0)20 3080 6000; info@mhra.gov.uk), ref: CTA 57954/0001/001-0001 |
| Health condition(s) or problem(s) studied | Rheumatoid arthritis (RA), other inflammatory diseases, or pain |
| Intervention | In Part 1, up to 56 volunteers will be split into seven cohorts. Each cohort will receive two oral doses of the test medicine at different dose levels, or placebo, 12 hours apart and in the fasted state. Following a minimum 7-day washout period Cohort 4 only will take part in Period 2, where volunteers will receive 2 oral doses of the test medicine, or placebo, 12 hours apart in the fed state. Volunteers will be discharged 48 hours post morning dose in each study period and will return for a follow-up visit 3-5 days after discharge. Cohort 1: 10 mg dose twice a day on one occasion Cohort 2: 30 mg dose twice a day on one occasion Cohort 3: 90 mg dose twice a day on one occasion Cohort 4: 60 mg dose twice a day on two occasions Cohort 5: 120 mg dose twice a day on one occasion Cohort 6: 140 mg dose twice a day on one occasion Cohort 7: 270 mg dose twice a day on one occasion In Part 2, up to 48 volunteers will be split into four cohorts. Based on Part 1 results, each cohort will receive either one or two oral doses a day of the test medicine, or placebo, for 7 consecutive days, in the fasted state. Volunteers will be discharged 48 hours post final dose and will return for a follow-up visit 3-5 days after discharge. Cohort 1: 90 mg dose twice a day for 7 consecutive days Cohort 2: 180 mg dose twice a day for 7 consecutive days Cohort 3: 270 mg dose twice a day for 7 consecutive days Cohort 4: no interventions were administered |
| Intervention type | Drug |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | DES-9384 |
| Primary outcome measure(s) |
Safety and tolerability of DES-9384 measured using incidence of adverse events (AEs), physical examinations, and change from baseline for vital signs, ECGs and clinical laboratory tests at Day -1 until the follow-up visit. The incidence of AEs is not measured at granular timepoints but for the other measurements they are as follows: |
| Key secondary outcome measure(s) |
1. PK parameters: Tlag, Tmax, Cmax, C12, C24, AUC(0-12), AUC(0-24), AUC(0-last), AUC(0-tau), AUC(0-inf),T1/2, Aeu and associated renal clearance (CLr) for DES-9384, as applicable measured using plasma concentration data (Parts 1 and 2) and urine concentration data (Part 1 only) at Day -1 (Part 1) or Day 1 (Part 2) until discharge |
| Completion date | 29/02/2024 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 55 Years |
| Sex | All |
| Target sample size at registration | 104 |
| Total final enrolment | 88 |
| Key inclusion criteria | 1. Must provide written informed consent 2. Must be willing and able to communicate and participate in the whole study 3. Aged 18 to 55 years inclusive at the time of signing informed consent 4. Must agree to adhere to the contraception requirements 5. Healthy males or non-pregnant, non-lactating females of non-childbearing potential 6. Body mass index (BMI) of 18.0 to 32.0 kg/m2 as measured at screening 7. Weight ˂110 kg at screening |
| Key exclusion criteria | 1. Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients 2. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active 3. History of serious adverse reaction or serious hypersensitivity to the challenge agent (AITC) or vehicle (mineral oil) (subjects participating in the skin challenge assessments in Part 1 Cohort 2, 4 or 7 only) 4. History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease (intermittent history of vomiting or diarrhoea), neurological or psychiatric disorder, as judged by the investigator 5. Subjects with a history of cholecystectomy or gall stones 6. History of dermatographism (subjects participating in the skin challenge assessments in Part 1 Cohort 2, 4 or 7 only) 7. Presence or history of clinically significant skin disorders, as judged by the investigator (Part 1 only) 8. History of trauma or surgery (laceration repair is not excluded) to the forearm but not including wrist or hand injury/surgery (subjects participating in the skin challenge assessments in Part 1 Cohort 2, 4 or 7 only) 9. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening 10. Excessive tattoos, forearm hair or other physical or behavioural characteristics which may interfere with PD objectives of the study, as determined and agreed by the PI and sponsor (subjects participating in the skin challenge assessments in Part 1 Cohort 2, 4 or 7 only) Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator. Subjects with Gilbert’s Syndrome are not allowed. 11. The following laboratory evaluations at screening or first admission, including: − RBC or haemoglobin < lower limit of normal (LLN) − ALT or AST > upper limit of normal (ULN) 12. Blood pressure (supine) at screening or first admission outside the range of 90 to 140 mmHg systolic or 50 to 90 mmHg diastolic; and heart rate outside the range of 50 to 90 bpm. 13. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results 14. Evidence of renal impairment at screening, as indicated by an estimated glomerular filtration rate (eGFR) of <80 mL/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI; 2009) equation 15. Females of childbearing potential including those who are pregnant or lactating (all female subjects must have a negative highly sensitive serum and urine pregnancy test at screening and first admission, respectively). 16. Lower than 100% dermal blood perfusion during application of AITC to the volar surface of both forearms, as assessed during screening (subjects participating in the skin challenge assessments in Part 1 Cohort 2, 4 or 7 only) 17. History or presence of known structural cardiac abnormalities, family history of long QT syndrome, cardiac syncope or recurrent, idiopathic syncope, or exercise-related clinically significant cardiac events. Any clinically significant abnormalities in rhythm, conduction or morphology of resting 12-lead ECG or clinically important abnormalities that may interfere with the interpretation of QT interval changes or QTcF >450 msec. 18. Subjects who have received any IMP in a clinical research study within the 90 days prior to the first dosing occasion or less than 5 elimination half-lives prior to Day 1, whichever is longer 19. Subjects who have previously been administered IMP in this study. Subjects who have taken part in Part 1 are not permitted to take part in Part 2 20. Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood 21. Subjects who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies (other than up to 4 g of paracetamol per day or HRT) in the 14 days before first IMP administration. Exceptions may apply, as determined by the investigator, if each of the following criteria are met: medication with a short half-life if the washout is such that no PD activity is expected by the time of dosing with IMP; and if the use of medication does not jeopardise the safety of the trial subject; and if the use of medication is not considered to interfere with the objectives of the study 22. Subjects who have had a COVID-19 vaccine 72 h prior to dosing 23. History of any drug or alcohol abuse in the past 2 years 24. Regular alcohol consumption in males >21 units per week and in females >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type) 25. A confirmed positive alcohol breath test at screening or first admission 26. Current smokers and those who have smoked within the last 12 months 27. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or first admission 28. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months 29. Confirmed positive drugs of abuse test result 30. Subjects who do not agree to eat a high-fat breakfast (Part 1 Cohort 4 only) 31. Male subjects with pregnant or lactating partners 32. Subjects who are, or are immediate family members of, a study site or sponsor employee 33. Failure to satisfy the investigator of fitness to participate for any other reason |
| Date of first enrolment | 13/07/2023 |
| Date of final enrolment | 29/02/2024 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
Ruddington Fields
Ruddington
Nottingham
NG11 6JS
England
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|
Editorial Notes
20/08/2026: The information for which publication was previously deferred has been added to the following fields:
1. Public and scientific title.
2. Study design.
3. Study objectives.
4. Interventions.
5. Drug/device/biological/vaccine name(s).
6. Primary and secondary outcome measures.
7. Key inclusion and exclusion criteria.
8. Final enrolment number.
9. Plain English summary of protocol.
10. The date of first enrolment was changed from 27/06/2023 to 13/07/2023
11. The date of final enrolment was changed from 14/03/2024 to 29/02/2024
12. The completion date was changed from 24/03/2024 to 29/02/2024
13. Ethics approval.
09/05/2023: Trial's existence confirmed by the MHRA.
