A study to compare a single dose of M923, EU-sourced Humira or US-sourced Humira in healthy volunteers
| ISRCTN | ISRCTN70649397 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN70649397 |
| EudraCT/CTIS number | 2014-001043-20 |
| IRAS number | 164168 |
| Secondary identifying numbers | 911301, IRAS 164168 |
- Submission date
- 11/02/2015
- Registration date
- 16/02/2015
- Last edited
- 02/09/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English summary of protocol
Background and study aims
This is a study to investigate and compare the pharmacokinetics (measuring drug levels in the blood over time), safety, tolerability and immunogenicity (blood tests to check the body's immune response to the drug) following single doses (40mg) of three different preparations of a human monoclonal antibody given by injection. This anti-inflammatory human monoclonal antibody is used to treat various autoimmune diseases such as rheumatoid arthritis and psoriasis. Two different preparations are marketed for use in the USA (USHumira) and Europe (EUHumira). Baxter Innovations GmbH (part of The Baxter Healthcare Corporation) is developing a monoclonal antibody M923 to be a similar biological medicinal product (biosimilar) to the marketed adalimumab (USHumira and EUHumira) preparations. M923 has not been given to humans before and in this study will be compared with the 2 marketed USHumira and EUHumira preparations.
Who can participate?
Healthy adults aged 18-55
What does the study involve?
After an initial review of their medical condition to ensure that they meet study requirements to take part, the participants are randomly allocated into one of two groups. Those in group 1 are given a single dose of M923. Those in group 2 are given a single dose of USHumira. Those in group 3 are given a single dose of EUHumira. The study takes place over about 9 months and involves a screening visit, a period where volunteers will be inpatients and must stay in the clinic (up to eight nights), several outpatient visits and a final follow up visit.
What are the possible benefits and risks of participating?
There is no medical benefit to the subjects as they are healthy volunteers. The possibility of side effects from the preparations of Humira and M923 is minimal not only due to the single dose used but also because previous studies with Adalimumab (Humira®) in healthy subjects demonstrated no treatment related serious side effects.
Where is the study run from?
It is a multisite study with three sites in London, Wales, and Northern Ireland
When is the study starting and how long is it expected to run for?
December 2014 to August 2015
Who is funding the study?
Baxter Innovations GmbH (Austria)
Who is the main contact?
Dr Barbara Valenta Singer
barbara_valenta_singer@baxter.com
Contact information
Scientific
Baxter Innovations GmbH
Donau-City-Strasse 7
Vienna
1220
Austria
| Phone | +43 (0)1 20100 2472930 |
|---|---|
| barbara_valenta_singer@baxter.com |
Study information
| Study design | Multi-centre randomised double-blind three-arm parallel-group single-dose study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Other |
| Study type | Other |
| Participant information sheet | Not available in web format please use contact details to request a subject information sheet. |
| Scientific title | A randomized, double-blind, three-arm, parallel group, single-dose study to compare the pharmacokinetics, safety, tolerability, and immunogenicity of three formulations of adalimumab (M923, US Sourced Humira and EU Sourced Humira) in healthy subjects |
| Study objectives | 1. The primary objective is to investigate and compare the pharmacokinetic (PK) profiles of M923, United States of America (US) sourced Humira and European Union (EU) sourced Humira in healthy subjects. 2. The secondary objective is to investigate the safety, tolerability, and immunogenicity of M923, US sourced Humira and EU sourced Humira in healthy subjects. |
| Ethics approval(s) | NRES Committee London - London Bridge, 11/12/2014, ref: 14/LO/2007 |
| Health condition(s) or problem(s) studied | Healthy adult volunteers |
| Intervention | Three formulations of adalimumab (M923, US Sourced Humira and EU Sourced Humira) |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | M923 (adalimumab), US sourced Humira (adalimumab) and EU sourced Humira (adalimumab) |
| Primary outcome measure | 1. Observed maximum concentration (Cmax) 2. Area under the serum concentration-time curve from time zero to 336 hours [AUC(0-336)] 3. Area under the serum concentration-time curve from time zero extrapolated to infinity [AUC(0-inf)] PK blood samples will be taken pre-dose and up to and including Day 71 post-dose. |
| Secondary outcome measures | 1. The area under the serum concentration-time curve from time zero to 1344 hours [AUC(0-1344)] 2. Area under the serum concentration-time curve from time zero to time of the last quantifiable concentration [AUC(0-last)] 3. Time of maximum concentration (tmax) 4. Terminal rate constant (λz) 5. Terminal half- life (t1/2) 6. Apparent volume of distribution following extravascular dosing (Vz/F) 7. Apparent volume of distribution at distribution equilibrium (Vss/F) 8. Apparent systemic clearance after extravascular dosing (CL/F) 9. Area under the concentration-time curve extrapolated from time t to infinity as a percentage of total AUC (%AUCex) Vital signs will be performed pre-dose and post-dose - ECGs will be performed pre-dose and post-dose. Clinical laboratory tests: pre-dose and post-dose. Adverse events: Day-1 till last visit. Injection site evaluation Day-1 till last visit |
| Overall study start date | 11/12/2014 |
| Completion date | 26/08/2015 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 324 |
| Total final enrolment | 324 |
| Key inclusion criteria | 1. Male or females of non-childbearing potential aged 18 to 55 years, inclusive 2. Healthy as determined by pre study medical history, physical examination, vital signs and 12-lead ECG 3. Clinical laboratory test results that are not clinically significant and are acceptable to the investigator at screening and admission to the clinical unit (Day -1) 4. Body weight between 60.0 and 100.0 kg and a body mass index (BMI) between 18.5 and 29.9 kg/m2, inclusive 5. Male subjects must have been vasectomized with confirmation of sterility or be willing to comply with the contraception restrictions for this study 6. Female subjects must have a negative pregnancy test at screening and on admission to the clinical unit (Day -1), must not be lactating, and must be of non-childbearing potential 7. Has smoked ≤10 cigarettes or 3 cigars or 3 pipes/day for at least 3 months prior to screening and is willing to comply with smoking restrictions during confinement at the study center 8. Willing and able to comply with the requirements of the study 9. Willing and able to sign a written informed consent |
| Key exclusion criteria | 1. Clinically significant allergic or hypersensitivity conditions 2. Tuberculosis, invasive systemic fungal infections, other severe opportunistic infections, recent serious infection, recent or recurrent herpes zoster infection, chronic or recurrent infections 3. Recent or planned other investigational trial participation 4. Alcohol abuse or drug abuse 5. Recent use of any prescribed or non prescribed medication other than paracetamol, vitamins and for females, hormone replacement therapy 6. Congestive heart failure 7. Signs or symptoms of demyelinating disease 8. Cancer 9. Impaired liver function 10. Immunodeficiency or other clinically significant immunological disorders 11. Anti-citrullinated protein antibodies at screening 12. Anti-drug antibodies to adalimumab at screening 13. Clinically relevant history or presence of medical disorders as judged by the investigator 14. Recent or planned receipt during the study of a live vaccine 15. Medical dietary restrictions 16. Subjects who cannot communicate reliably |
| Date of first enrolment | 11/12/2014 |
| Date of final enrolment | 30/04/2015 |
Locations
Countries of recruitment
- England
- Northern Ireland
- United Kingdom
- Wales
Study participating centres
London
SE11YR
United Kingdom
Merthyr Tydfil
CF48 4DR
United Kingdom
Belfast
BT2 7B
United Kingdom
Sponsor information
Industry
Donau-City-Strasse 7
Vienna
1220
Austria
"ROR" |
https://ror.org/013xmn143 |
|---|
Funders
Funder type
Industry
Private sector organisation / For-profit companies (industry)
- Location
- Austria
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | To be confirmed at a later date 2016 abstract in https://ard.bmj.com/content/75/Suppl_2/495.3 (added 02/09/2020) |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
02/09/2020: IRAS Project ID, abstract and total final enrolment number added.
14/09/2017: No publications found, verifying study status with principal investigator.
