A Phase I randomized, open-label pharmacokinetic comparability study comparing pre- and post-change teclistamab in participants with relapsed/refractory multiple myeloma
| ISRCTN | ISRCTN46766641 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN46766641 |
| EudraCT/CTIS number | 2023-508426-10 |
| IRAS number | 1009491 |
| ClinicalTrials.gov number | NCT06425991 |
| Secondary identifying numbers | 64007957MMY1008, IRAS 1009491, CPMS 60389 |
- Submission date
- 11/04/2024
- Registration date
- 22/05/2024
- Last edited
- 13/12/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English Summary
Background and study aims
Multiple myeloma (MM) is a blood cancer that forms in a type of white blood cell (WBC) called plasma cells. Drugs that activate T-cells (type of WBCs) to attack cancer cells may be an effective way to destroy them. Teclistamab binds to a protein called cluster of differentiation 3 (CD3) receptor, which is found on T cells. It also binds to a protein called B-cell maturation antigen (BCMA), which is found on myeloma cells and some B cells (another type of WBC). This activates the T cells and leads to the killing of myeloma cells. In this study, the researchers want to learn more about how teclistamab made from the current commercial manufacturing process (pre-change) gets absorbed, distributed in the body, and excreted (pharmacokinetics) compared to the teclistamab made from a new manufacturing process (post-change).
Who can participate?
Patients aged 18 years or older with relapsed or refractory multiple myeloma. Cancer is called relapsed if it comes back after treatment and is called refractory if it does not respond to treatment.
What does the study involve?
At the start of the study, study doctors will confirm if the participants can take part in the study. They will divide participants into either of the two treatment groups in a random way to receive the treatment in 28-day cycles:
Group A: Pre-change teclistamab as an injection under the skin
Group B: Post-change teclistamab as an injection under the skin
Participants will be followed up on their overall health throughout the study. During the study, some tests such as blood and urine tests, imaging scans, and bone marrow testing will be performed. Blood samples will be taken at multiple timepoints to see how the body responds to treatment. Disease status will be checked based on International Myeloma Working Group (IMWG) criteria for multiple myeloma. Side effects will be recorded until the study ends (up to about 3 years).
What are the possible benefits and risks of participating?
Participants may or may not receive any benefit from taking part in this study but the information that is learned from the study may help people with multiple myeloma in the future. This is a Phase I study in which pharmacokinetics (the process by which a drug gets absorbed, distributed in the body, and excreted) of pre-change teclistamab will be compared to post-change teclistamab. However, no differences are expected.
The expected risks for teclistamab includes inflammation condition that may occur after treatment with some types of immunotherapy, such as monoclonal antibodies (cytokine release syndrome), Neurological side effects may occur that include headaches or a condition of brain (immune effector cell-associated neurotoxicity syndrome), reduction in blood cells (cytopenias), low protein in blood that fights infection (hypogammaglobulinemia), infections, injection-site reactions.
The participant information sheet and informed consent form, which will be signed by every participant agreeing to take part in the study, includes a detailed section outlining the risks of participating in the study. Participants may have none, some, or all of the possible side effects listed, and they may be mild, moderate, or severe. To minimise the risk associated with taking part, participants are frequently reviewed for any side effects and other medical events. If they have any side effects, are worried about them, or have any new or unusual symptoms, participants will be encouraged to talk with their study doctor. The study doctor will also be monitoring for side effects and will provide appropriate medical care. There may also be side effects that the researchers do not expect or do not know about and that may be serious. Many side effects go away shortly after the intervention ends. However, sometimes side effects can be serious, long-lasting, or permanent. If a severe side effect or reaction occurs, the study doctor may need to stop the procedure. The study doctor will discuss the best way of managing any side effects with participants. There is always a chance that an unexpected or serious side effect may happen. This can happen to people who take this or any other drug.
Where is the study run from?
Janssen-Cilag International NV (Netherlands)
When is the study starting and how long is it expected to run for?
April 2024 to December 2027
Who is funding the study?
Janssen-Cilag International NV (Netherlands)
Who is the main contact?
Dr Lacramioara Arvata, JanssenUKRegistryQueries@its.jnj.com
Contact information
Scientific
50-100 Holmers Farm Way
High Wycombe
HP12 4DP
United Kingdom
| Phone | +44 (0)7881 011 932 |
|---|---|
| JanssenUKRegistryQueries@its.jnj.com |
Principal Investigator
Derriford Road
Plymouth
PL6 8DH
United Kingdom
Study information
| Study design | Open randomized controlled parallel-group trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Safety, Efficacy |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | A Phase I randomized, open-label pharmacokinetic comparability study comparing pre- and post-change teclistamab in participants with relapsed/refractory multiple myeloma |
| Study acronym | MajesTEC-10 |
| Study hypothesis | Primary objective: The primary objective of this study is to evaluate the pharmacokinetic (PK) comparability of teclistamab monotherapy using teclistamab from the pre-change manufacturing process with that of the post-change manufacturing process. Secondary objectives: 1. To compare the immunogenicity of pre-change teclistamab and post-change teclistamab 2. To compare the safety profile of pre-change teclistamab and post-change teclistamab 3. To compare the efficacy of pre-change teclistamab and post-change teclistamab |
| Ethics approval(s) | Approved 21/05/2024, North East - Tyne & Wear South Research Ethics Committee (NHSBT Newcastle Blood Donor Centre; Holland Drive, Newcastle upon Tyne, NE2 4NQ, United Kingdom; +44 (0)20 710 48120; tyneandwearsouth.rec@hra.nhs.uk), ref: 24/NE/0076 |
| Condition | Relapsed/refractory multiple myeloma |
| Intervention | Participants will be divided into either of the two treatment groups in a random way to receive the treatment in 28-day cycles: Arm A: Participants will receive teclistamab monotherapy (made from the pre-change manufacturing process) as an injection under the skin for all step-up and treatment doses until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent to treatment, or the end of the study, whichever occurs first. Arm B: Participants will receive teclistamab monotherapy (made from the post-change manufacturing process) as an injection under the skin for all step-up and treatment doses until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent to treatment, or the end of the study, whichever occurs first. Participants will be followed up for their overall health throughout the study. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic, Pharmacodynamic |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | Teclistamab |
| Primary outcome measure | PK comparability between pre-change teclistamab and post-change teclistamab: 1. Maximum observed serum concentration (Cmax) of teclistamab after the first treatment dose. 2. Area under serum concentration versus time curve (AUCtau) of teclistamab first treatment dose. AUCtau is defined as the area under the concentration-time curve during the dosing interval of teclistamab (after the first treatment dose). 3. Observed serum concentration immediately prior to the next study treatment administration (Ctrough) on Cycle 3 Day 1 |
| Secondary outcome measures | 1. Number of participants with anti-drug antibodies (ADAs) to teclistamab, reported up to approximately 3 years 2. Number of participants with adverse events (AEs) by severity, reported up to approximately 3 years 3. Number of participants with serious adverse events (SAEs) by severity, reported up approximately 3 years 4. Number of participants with abnormal laboratory results, such as hematology and chemistry, reported up to approximately 3 years 5. Percentage of participants with overall response (partial response [PR] or better), defined as participants who have a PR or better prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 criteria - measured up to approximately 3 years 6. Percentage of participants with complete response (CR) or better response, defined as participants who achieve a CR or better response prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 criteria - measured up to approximately 3 years 7. Percentage of participants with very good partial response (VGPR) or better response, defined as participants who achieve a VGPR or better response prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 criteria - measured up to approximately 3 years 8. Characterization of changes in sBCMA as a pharmacodynamic marker measured using soluble BCMA blood concentrations, reported up to approximately 3 years |
| Overall study start date | 09/04/2024 |
| Overall study end date | 30/12/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 100 |
| Participant inclusion criteria | 1. Documented diagnosis of multiple myeloma as defined by the criteria below: 1.1. Multiple myeloma diagnosis according to International Myeloma Working Group (IMWG) diagnostic criteria 1.2. Measurable disease at screening as defined by any of the following: 1.2.1. Serum M-protein level greater than or equal to (≥)0.5 grams per deciliter (g/dL) (central laboratory); or 1.2.2. Urine M-protein level ≥200 milligrams (mg)/24 hours (central laboratory) or 1.2.3. Serum immunoglobulin free light chain ≥10 milligrams per deciliter (mg/dL) (central laboratory) and abnormal serum immunoglobulin kappa lambda free light chain ratio 2. Received one to three prior lines of antimyeloma therapy, including a minimum of two consecutive cycles each of a PI, lenalidomide, and an anti-CD38 monoclonal antibody (or minimum of six doses if anti-CD38 monoclonal antibody was only part of a maintenance regimen) in any prior line. 3. Documented evidence of progressive disease or failure to achieve a response to the last line of therapy based on the investigator's determination of response by International Myeloma Working Group (IMWG) criteria 4. Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2 5. A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test at screening and within 24 hours of the start of study treatment and must agree to further serum or urine pregnancy tests during the study |
| Participant exclusion criteria | 1. Received any bispecific antibody and/or chimeric antigen receptor T cell (CAR-T) cell therapy 2. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients 3. Received a live, attenuated vaccine within 4 weeks before the first dose of the study drug. Non-live or non-replicating vaccines authorized for emergency use by local health authorities are allowed 4. Central nervous system involvement or clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole-brain magnetic resonance imaging (MRI) and lumbar cytology may be required 5. Participant had major surgery or had significant traumatic injury within 2 weeks prior to randomization, or will not have fully recovered from surgery, or has major surgery planned during the time the participant is expected to be treated in the study |
| Recruitment start date | 13/05/2024 |
| Recruitment end date | 31/01/2025 |
Locations
Countries of recruitment
- Australia
- Canada
- England
- France
- Germany
- Italy
- Korea, South
- Poland
- Spain
- United Kingdom
- United States of America
Study participating centres
Manchester
M20 4BX
United Kingdom
Derriford
Plymouth
PL6 8DH
United Kingdom
Colney
Norwich
NR4 7UY
United Kingdom
Hammersmith
London
W12 0HS
United Kingdom
Sponsor information
Industry
Archimedesweg 29
Leiden
2333 CM
Netherlands
| Phone | +31 (0)71 524 21 06 |
|---|---|
| ClinicalTrialsEU@its.jnj.com |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 30/12/2028 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | 1. Peer-reviewed scientific journals 2. Internal report 3. Conference presentation 4. Publication on website 5. Submission to regulatory authorities Study results will be available via publication in scientific journals, the EudraCT database and presentation at scientific meetings. Results will be made available to participants via a Plain Language Summary a year after the end of the study. The summary will describe the results regardless of study outcome in language that is understandable to the general public. It will not contain individual participant results or their personal information. A copy of the Summary will be provided to the REC. |
| IPD sharing plan | The data sharing policy of the Janssen Pharmaceutical Companies of Johnson and Johnson is available at https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through the Yale Open Data Access (YODA) Project site at yoda.yale.edu. |
Editorial Notes
13/12/2024: The following
1. The recruitment end date was changed from 02/12/2024 to 31/01/2025.
2. The ClinicalTrials.gov number was added.
04/06/2024: Ethics approval details added.
04/06/2024: Internal review.
22/05/2024: ISRCTN received notification of combined HRA/MHRA approval for this trial on 22/05/2024.
11/04/2024: Study's existence confirmed by the HRA.
