Nipocalimab in moderate to severe Sjogren's disease
| ISRCTN | ISRCTN14534389 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14534389 |
| EudraCT/CTIS number | 2024-513965-38 |
| IRAS number | 1010975 |
| Secondary identifying numbers | 80202135SJS3001, CPMS 61912 |
- Submission date
- 12/11/2024
- Registration date
- 31/12/2024
- Last edited
- 07/05/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Musculoskeletal Diseases
Plain English Summary
Background and study aims
Sjogren's Disease (SjD) is a chronic (long-term), progressive, autoimmune disease (body’s immune system attacking normal tissue) in which circulating immunoglobulin (IgG) autoantibodies* activate the immune system including B-cells (type of white blood cells called lymphocytes) causing blood vessel damage & local destruction of exocrine glands**causing dryness, fatigue, pain & problems of skin, muscle & internal organs. Current approved treatments only alleviate the symptoms of dryness. There is no treatment approved for individuals with SjD & guidelines recommend use of immunosuppressive therapy (treatment to suppress body’s immune system).
*Type of proteins produced by immune system that mistakenly attack body's own cells & tissues.
**Glands responsible for producing tears & saliva.
Nipocalimab (JNJ-80202135/JNJ-86507083) is a monoclonal antibody that selectively blocks the IgG binding site called endogenous neonatal fragment crystallizable receptor resulting in decrease in circulating IgG, thus reducing inflammatory immune response to the harmful IgG in the body.
In this study, researchers want to learn how well nipocalimab works and how safe it is in participants with moderate to severe SjD compared to placebo.
Who can participate?
Patients with SjD.
What does the study involve?
Participants will be randomly (by chance) assigned to one of the 2 identical studies (conducted under this single protocol).
Study will consist of:
1. Screening period (up to Week 6)
2. Double blind treatment period (up to Week 48): Participants in the 2 studies will be randomly assigned to arms below to receive assigned intervention:
o Arm A: Nipocalimab
o Arm B: Placebo
3. Open-label extension (up to Week 150): Participants will be given an option to continue nipocalimab.
4. Safety follow-up (up to Week 156)
Safety assessments include monitoring of adverse events (AEs), SAEs, participant & investigator reported questionnaires, & blood tests. All side effects will be recorded till the study ends (approximately 3 years).
What are the possible benefits and risks of participating?
Benefits:
Not provided at time of registration
Risks:
There is no established benefit to participants of this study. Based on scientific theory, taking nipocalimab may improve Sjogren's Disease. However, this cannot be guaranteed because nipocalimab is still under investigation as a treatment and it is not known whether nipocalimab will work.
In addition, if participants are put into the placebo treatment group they will not receive nipocalimab and will only receive placebo during the double blind period of this study.
Participants may experience some benefit from participation in the study that is not due to receiving study drug, but due to regular visits and assessments monitoring overall health. Participation may help other people with Sjogren's Disease in the future. In addition, all patients are allowed to continue standard of care background therapy.
Participants may have side effects from the drug or procedures used in this study that may be mild to severe and even life-threatening, and they can vary from person to person. The most common, potential risks are getting side effects such as infections caused due to decreased serum IgG concentrations, reduced effectiveness of routine vaccines due to decreased IgG, activation of latent virus due to decreased IgG, hypoalbuminemia (low levels of albumin, a blood protein), injection-site reactions, hypersensitivity (allergic reactions), drug-drug interactions and increase in cholesterol after administering nipocalimab or placebo. There are other, less frequent potential risks. The participant information sheet and informed consent study drug or placebo form, which will be signed by every participant agreeing to participate in the study, includes a detailed section outlining the potential risks to participating in the study.
Not all possible side effects and risks related to nipocalimab are known at this moment. During the study, the sponsor may learn new information about nipocalimab. The study doctor will tell participants as soon as possible about any new information that might make them change their mind about being in the study, such as new risks.
To minimise the risk associated with taking part in the study, participants are frequently reviewed for any side effects and other medical events. Participants are educated to report any such events to their study doctor who will provide appropriate medical care. Any serious side effects that are reported to the sponsor are thoroughly reviewed by a specialist drug safety team.
There are no costs to participants to be in the study. The sponsor will pay for the study drug and tests that are part of the study. The participant will receive reasonable reimbursement for study-related costs (e.g., travel/parking costs).
Where is the study run from?
Janssen Research & Development, LLC (Netherlands)
When is the study starting and how long is it expected to run for?
November 2024 to April 2030
Who is funding the study?
Janssen Research & Development, LLC (Netherlands)
Who is the main contact?
medinfo@its.jnj.com
JanssenUKregistryQueries@its.jnj.com
Contact information
Scientific
50-100 Holmers Farm Way
High Wycombe
HP12 4DP
United Kingdom
| Phone | +44 1494567444 |
|---|---|
| medinfo@its.jnj.com |
Principal Investigator
Marlborough Road
Swindon
SN3 6BB
United Kingdom
| Phone | +44 1793 604314 |
|---|---|
| elizabeth.price5@nhs.net |
Public
50-100 Holmers Farm Way
High Wycombe
HP12 4DP
United Kingdom
| JanssenUKregistryQueries@its.jnj.com |
Study information
| Study design | Interventional double blind randomized placebo controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Safety, Efficacy |
| Scientific title | A randomized, placebo-controlled, double-blind, multicenter phase 3 protocol to assess the efficacy and safety of nipocalimab in adults with moderate to severe Sjogren's disease (SjD) |
| Study acronym | DAFFODIL |
| Study hypothesis | Primary objective: To evaluate how well nipocalimab works as compared to placebo in participants with moderate to severe Sjögren's Disease (SjD). Secondary objectives: 1. To further evaluate how well nipocalimab works as compared to placebo in participants with moderate to severe SjD. 2. To evaluate the safety of nipocalimab compared to placebo in participants with moderate to severe SjD. 3. To assess long-term safety and efficacy of nipocalimab during the open label long-term extension (LTE). |
| Ethics approval(s) |
Approved 23/12/2024, East Midlands – Nottingham 2 REC (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 207 104 8065; nottingham2.rec@hra.nhs.uk), ref: 24/EM/0261 |
| Condition | Sjogrens Syndrome |
| Intervention | Participants will be randomly assigned via an online tool to one of the 2 identical studies (conducted under this single protocol). The study will consist of: 1. Screening period (up to Week 6) 2. Double blind treatment period (up to Week 48): Participants in the 2 studies will be randomly assigned to the arms below to receive assigned intervention: o Arm A: Nipocalimab o Arm B: Placebo 3. Open-label extension (up to Week 150): Participants will be given an option to continue nipocalimab. 4. Safety follow-up (up to Week 156) Participants will receive either Nipocalimab or Placebo subcutaneously (SC) along with standard of care treatments. At the Week 48 visit, eligible participants from both studies will have the option to enter an open-label long-term extension (OLE) phase, where they will receive nipocalimab until Week 143 or until the study intervention is discontinued and participants opt to withdraw from the study. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic, Pharmacodynamic, Pharmacogenomic, Therapy |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Nipocalimab |
| Primary outcome measure | Change from Baseline in Clinical European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (ClinESSDAI) Score at Week 48. |
| Secondary outcome measures | 1. Minimal Clinically Important Improvement is measured using ClinESSDAI Score from Baseline to Week 48 2. Systemic disease activity in Participants with High Immunoglobulin (IgG) Levels at Baseline is measured using ClinESSDAI Score from baseline to Week 48 3. Systemic disease activity is measured ClinESSDAI Score from Baseline to Week 8 4. Glandular function change is measured using Stimulated Salivary Flow Rate from Baseline in at Week 48 5. Dryness symptoms will be measured using the Sjogren’s Symptoms Dryness Score from Baseline to Week 48 6. Joint pain will be measured using the Sjogren’s Symptoms Joint Pain Score from Baseline to Week 48 7. Severity of dryness, fatigue and pain associated with primary Sjogren’s Syndrome will be measured using the EULAR Sjogren’s Syndrome Patient Reported Index (ESSPRI) Score from Baseline to Week 48 8. Fatigue is measured using the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT) Fatigue Score from Baseline to Week 48 |
| Overall study start date | 07/11/2024 |
| Overall study end date | 17/04/2030 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 600 |
| Participant inclusion criteria | 1. Medically stable on the basis of physical examination, medical history, vital signs, 12-lead electrocardiogram (ECG) and clinical laboratory tests performed at screening 2. Meets criteria for diagnosis of SjD by the 2016 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria 3. Seropositive for antibodies to Ro/SSA at screening 4. Total ClinESSDAI score greater than or equal to (>=) 5 at screening 5. Participants of childbearing potential must have a negative highly sensitive serum (beta-hCG) pregnancy test at screening and a negative urine pregnancy test at Week 0 prior to randomization |
| Participant exclusion criteria | 1. Has a history of severe, progressive and/or uncontrolled hepatic, gastrointestinal, renal, pulmonary, cardiovascular, psychiatric, neurological or musculoskeletal disorder, hypertension, and/or any other medical or uncontrolled autoimmune disorder or clinically significant abnormalities in screening laboratory 2. Known allergies, hypersensitivity, or intolerance to nipocalimab or its excipients or excipients used in the placebo formulation 3. Has any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her SjD or has a family history of congenital or hereditary immunodeficiency 4. Has shown a previous severe immediate hypersensitivity reaction, such as anaphylaxis, to therapeutic proteins (for example [e.g.], monoclonal antibodies, intravenous immunoglobulin) 5. Has any unstable or progressive manifestation of SjD that is likely to warrant escalation in therapy beyond permitted background medications |
| Recruitment start date | 27/03/2025 |
| Recruitment end date | 25/02/2027 |
Locations
Countries of recruitment
- Argentina
- Austria
- Brazil
- Bulgaria
- China
- Denmark
- France
- Germany
- Hungary
- Italy
- Japan
- Mexico
- Poland
- Portugal
- Romania
- Spain
- Taiwan
- United Kingdom
Study participating centre
United Kingdom
Sponsor information
Industry
Turnhoutseweg 30
Beerse
2340
Belgium
| RA-RNDUS-ClnclTrlsEU@its.jnj.com |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 17/04/2031 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Peer reviewed scientific journals Internal report Conference presentation Publication on website Submission to regulatory authorities Study results will be available via publication in scientific journals, the CTIS database & 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 www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) project site at yoda.yale.edu. |
Editorial Notes
07/05/2025: The recruitment start date was changed from 05/05/2025 to 27/03/2025.
28/01/2025: The ethics approval date was added and the recruitment start date was changed from 03/12/2024 to 05/05/2025.
20/01/2025: Internal review.
12/11/2024: Trial's existence confirmed by NHS HRA.
