A study of nipocalimab in participants with active idiopathic inflammatory myopathies
| ISRCTN | ISRCTN98762360 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN98762360 |
| EudraCT/CTIS number | 2021-005202-98 |
| IRAS number | 1005992 |
| ClinicalTrials.gov number | NCT05379634 |
| Secondary identifying numbers | 80202135IIM2001, IRAS 1005992, CPMS 53473 |
- Submission date
- 20/09/2022
- Registration date
- 19/05/2023
- Last edited
- 05/06/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Musculoskeletal Diseases
Plain English Summary
Background and study aims
Idiopathic inflammatory myopathies (IIM) are a group of rare diseases marked by long-standing inflammation and weakness of muscles used for movement. The primary symptoms of IIM are muscle weakness (which develops over a period of time), joint pain, and general tiredness. Nipocalimab is an antibody (a protein made in the body in response to a foreign substance) that blocks a specific antibody immunoglobulin G (IgG) binding site on the neonatal fragment crystallisable receptor (FcRn). FcRn is responsible for controlling IgG levels in the body. Nipocalimab blocks FcRn, resulting in a reduction of IgG which may reduce inflammation in muscles. This study is designed to see if nipocalimab is better than a placebo (dummy drug). This will be assessed by measuring how many participants achieve improvement in symptoms of IIM.
Who can participate?
Patients aged 18 years or above with IIM
What does the study involve?
The study will be conducted as:
1. Screening (6 weeks or less)
2. Double-blind* period (52 weeks): Participants will receive one of the two treatments below:
1. Nipocalimab: based on body weight as an injection in a vein at Week 0 up to Week 50
2. Placebo: similar to the nipocalimab treatment
Neither the researcher nor the participant knows which treatment is being given. Participants will also receive their current IIM medications. The amount of these medications may be reduced if the participant’s IIM is not getting worse.
3. Long-term extension (48 weeks): eligible participants will receive nipocalimab from Week 52 to Week 98, or until sponsor decision to stop treatment.
4. Safety follow-up (8 weeks after the last dose of study treatment).
During the study, some tests such as blood tests, physical examinations, and vital signs will be performed. Side effects will be recorded until the study ends (up to 112 weeks)
What are the possible benefits and risks of participating?
There is no established benefit to participants of this study. Based on scientific theory, taking nipocalimab may improve IIM. However, this cannot be guaranteed because nipocalimab is still under investigation as a treatment and it is not known whether nipocalimab will work. If participants are put into the placebo treatment group, they will not receive nipocalimab and will only receive placebo during this study. Participants may experience some benefit from participation in the study that is not due to receiving nipocalimab, but rather is due to regular visits and assessments monitoring overall health. Participation in the study may help other people with IIM in the future.
Participants may have side effects from the drug(s) 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 of nipocalimab are increased risk for infection, reduced effectiveness of routine vaccines, and activation of present virus due to decreased serum Immunoglobulin G (IgG) levels. There are other, less frequent risks. The participant information sheet and informed consent form, which will be signed by every participant agreeing to participate in the study, includes a detailed section outlining the known risks of 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 minimize the risk associated with taking part in the study, participants are frequently looked at and asked about any side effects and other medical events. Participants are educated to report any such events to the study doctor who will provide appropriate medical care. Any serious side effects that are reported to the sponsor are thoroughly reviewed by a 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 (for example, travel/parking costs).
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?
September 2022 to May 2027
Who is funding the study?
Janssen-Cilag International NV (Netherlands)
Who is the main contact?
Dr Catherine Najem, CNajem@ITS.JNJ.com
Contact information
Principal Investigator
250 Euston Rd
London
NW1 2PG
United Kingdom
| pedro.machado@nhs.net |
Scientific
Janssen-Cilag International NV
Archimedesweg 29
Leiden
2333
Netherlands
| Phone | + 1 (0)267 896 3538 |
|---|---|
| CNajem@ITS.JNJ.com |
Scientific
Janssen-Cilag International NV
Archimedesweg 29
Leiden
2333
Netherlands
| Phone | +1 (0)267 896 3538 |
|---|---|
| CNajem@ITS.JNJ.com |
Study information
| Study design | Double-blind randomized placebo-controlled parallel-group trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | A Phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of nipocalimab in participants with active idiopathic inflammatory myopathies |
| Study acronym | SPIREA |
| Study hypothesis | Main objectives: To see how effective nipocalimab is as compared to placebo in participants with active idiopathic inflammatory myopathies (IIM), a group of disorders marked by inflammation and weakness of the muscles used for movement (skeletal muscles). Secondary objectives: 1. To see how effective nipocalimab is as compared to placebo across other measures in participants with active IIM 2. To see how effective nipocalimab is as compared to placebo in: oral glucocorticoid reduction, disease improvement over time, and cutaneous (affecting skin) disease activity improvement (in dermatomyositis participants [inflammatory disease of muscle and skin]) 3. To assess the safety and tolerability of nipocalimab as compared to placebo 4. To see the effect of nipocalimab on patient-reported outcomes (PROs). PRO is a health outcome reported by the patient who experienced it 5. To see the pharmacokinetics (what the body does to the drug) and immunogenicity (immune response against the drug) of nipocalimab |
| Ethics approval(s) | Approved 29/11/2022, North West - Haydock Research Ethics Committee (3rd Floor - Barlow House, 4 Minshull Street, Manchester, M1 3DZ, UK; +44 (0)2071048248; haydock.rec@hra.nhs.uk), ref: 22/NW/0324 |
| Condition | Active idiopathic inflammatory myopathies (IIM) |
| Intervention | Nipocalimab arm: Participants will receive nipocalimab at Week 0 (Baseline) and then every 2 weeks (Q2W) up to Week 50 during the double-blind period. Participants on glucocorticoids (GC) at baseline will receive a stable dose of oral GC (prednisone or equivalent) from 4 weeks prior to the first administration of study intervention to Week 0. No changes in GC doses are allowed between Week 0 and Week 24. From Week 24 to Week 44, GC doses will be tapered. No changes to GC doses will be allowed from Week 44 to Week 52. Eligible participants will enter a long-term extension (LTE) period and continue receiving nipocalimab starting from Week 52 up to Week 98 and will be followed up to Week 106. Placebo arm: Participants will receive nipocalimab matching placebo at Week 0 (Baseline) and then Q2W up to Week 50 during the double-blind period. Participants on GC at baseline will receive a stable dose of oral GC (prednisone or equivalent) from 4 weeks prior to the first administration of study intervention to Week 0. No changes in GC doses are allowed between Week 0 and Week 24. From Week 24 to Week 44, GC doses will be tapered. No changes to GC doses will be allowed from Week 44 to Week 52. Eligible participants will enter the LTE period and continue receiving nipocalimab matching placebo Q2W starting from Week 52 up to Week 98 and will be followed up to Week 106. Stratified randomization will be used to minimize bias in the assignment of participants to intervention groups, to increase the likelihood that known and unknown participant attributes are evenly balanced across intervention groups, and to enhance the validity of statistical comparisons |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Nipocalimab |
| Primary outcome measure | Clinical improvement assessed as the percentage of participants who achieve at least minimal improvement (≥20) in International Myositis Assessment and Clinical Studies Total Improvement Score (IMACS TIS) and on ≤5 mg/day of oral prednisone (or equivalent) from week 44 through week 52. This assessment is conducted at week 52. |
| Secondary outcome measures | 1. Clinical improvement assessed as the percentage of participants who achieve at least minimal improvement (≥20) in the IMACS TIS standardised clinical response criteria score at week 24 2. Clinical improvement assessed using the IMACS TIS standardised clinical response criteria score at week 52 3. Clinical improvement assessed as the percentage of participants who achieve at least moderate improvement (≥40) in the IMACS TIS standardised clinical response criteria score at week 24 4. Evaluation of muscle strength using the change in Manual Muscle Testing (MMT)-8 score from baseline to week 52 5. Reduced use of oral GCs among participants on oral GC >5 mg/day at baseline based on the percentage of participants who achieve oral GC reduction to 5 mg/day of oral prednisone (or equivalent) at week 44 and maintain that reduction through week 52 6. Clinical improvement expressed as the percentage of participants who achieve at least minimal improvement (≥20) in IMACS TIS score on ≤5 mg/day of oral prednisone (or equivalent) from week 44 through week 52 reported from week 44 through week 52 7. Physical function assessed through change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF-20) at week 52 8. Clinical improvement assessed using the IMACS TIS standardised clinical response criteria score at week 24 9. Clinical improvement assessed as the percentage of participants who achieve at least moderate improvement (≥40) in the IMACS TIS standardised clinical response criteria score at week 52 10. Clinical improvement assessed as the percentage of participants who achieve at least major improvement (≥60) in IMACS TIS standardised clinical response criteria score at weeks 24 and 52 11. Muscle strength evaluated using the change in Manual Muscle Testing (MMT)-8 score from baseline to week 24 12. Overall disease activity evaluated using the change from baseline in the Physician Global Assessment (PhGA) tool at Weeks 24 and 52 13. Extramuscular global assessment using the Myositis Disease Activity Assessment Tool (MDAAT) at baseline, weeks 24 and 52 14. Serum muscle enzymes (creatine kinase [CK], alanine aminotransferase [ALT], aspartate aminotransferase [AST], lactate dehydrogenase [LDH], and aldolase) levels measured using a validated spectrophotometric method at baseline, Weeks 24 and 52 15. Percentage of participants on ≤5 mg/day of oral prednisone (or equivalent) from week 44 through week 52 16. Clinical improvement assessed as the percentage of participants on oral GC >5 mg/day at baseline who achieve at least minimal improvement (≥20) in IMACS TIS and achieve oral GC reduction to 5 mg/day at week 44 and maintain that reduction through week 52 17. Clinical improvement assessed as the percentage of participants who achieve at least minimal improvement (≥20) in IMACS TIS standardised clinical response criteria score from week 44 through week 52 (on ≤7.5 mg/day of oral prednisone or equivalent, from week 44 through week 52) 18. Percentage of participants on oral GC >7.5 mg/day at baseline who achieve oral GC reduction to ≤7.5 mg/day of oral prednisone (or equivalent) at week 44 and maintain that reduction through week 52 19. Clinical improvement assessed as the percentage of participants on oral GC >7.5 mg/day at baseline who achieve at least minimal improvement (≥20) in IMACS TIS standardised clinical response criteria score and achieve oral GC reduction to ≤7.5 mg/day at week 44 and maintain that reduction through week 52 20. Clinical improvement assessed using the IMACS TIS standardised clinical response criteria score up to week 106 21. Level of activity and damage in skin using the change in baseline in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) scale score at weeks 24 and 52 22. Level of activity and damage in skin using the change in baseline in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) scale score up to 106 weeks 23. Treatment-emergent adverse events (AEs) in study participants (percentage of total) recorded up to 106 weeks 24. Treatment-emergent serious adverse events (SAEs) in study participants (percentage of total) recorded up to 106 weeks 25. Functional status of the participant assessed by change from baseline in functional disability using the Health Assessment Questionnaire- disability Index (HAQ-DI) at weeks 24 and 52 26. Serum nipocalimab concentration over time derived using population pharmacokinetic (PK) modeling from baseline to week 98 27. Number of participants with anti-drug antibody (ADA), measured using a validated, specific and sensitive immunoassay method at baseline to week 106 28. Number of participants with neutralizing antibodies (Nabs) to nipocalimab, measured using a validated, specific and sensitive immunoassay method at baseline to week 106 |
| Overall study start date | 07/09/2022 |
| Overall study end date | 10/05/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 200 |
| Participant inclusion criteria | 1. Disease classification criteria: Participant meets the diagnostic criteria of probable or definite idiopathic inflammatory myopathies (IIM) based on 2017 The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for adult IIM at least 6 weeks prior to first administration of the study intervention 2. If a participant is on regular or as needed treatment with low potency topical glucocorticoids (GC) that are allowed in the study or topical tacrolimus (TAC) to treat skin lesions, the dose and frequency should be stable for greater than or equal to (>=) 4 weeks prior to first administration of the study intervention as well as maintained at the same dose until Week 52 of the study 3. Antibody positivity criteria: Any 1 of the myositis-specific antibodies (MSAs) positive: dermatomyositis (DM): anti-Mi-2 (Mi-2/nucleosome remodeling and deacetylase [NuRD] complex), anti-transcription intermediary factor 1-Gamma (TIF1-Gamma), anti-nuclear matrix protein 2 (NXP-2), anti-serious adverse event (SAE); anti-antimelanoma differentiation-associated gene 5 (MDA-5) antibodies. Or immune-mediated necrotizing myopathy (IMNM): anti-signal recognition particle (SRP) and anti- 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies. Or anti-synthetase syndrome (ASyS): anti-histidyl-ribonucleic acid [tRNA] synthetase (Jo-1), anti- threonyl-tRNA synthetase (PL7), anti- alanyl-tRNA synthetase (PL12), anti- isoleucyl-tRNA synthetase (OJ), and anti-glycyl-tRNA synthetase (EJ) antibodies. If all MSAs are negative or more than 1 MSA is positive (defined by the central laboratory) at screening, the tests should be repeated during the screening period. If the same results are observed at retesting, the participant should not be enrolled in the study |
| Participant exclusion criteria | 1. Has a juvenile myositis diagnosis and now ≥18 years old 2. Has cancer-associated myositis defined as cancer diagnosis within 3 years of myositis diagnosis except for cervical carcinoma in situ and non-melanoma skin cancer (squamous cell carcinoma, basal cell carcinoma of the skin) 3. Has comorbidities (for example, asthma, chronic obstructive pulmonary disease [COPD]) which have required three or more courses of oral GC within 1 year prior to screening 4. Has a history of primary immunodeficiency or secondary immunodeficiency not related to the treatment of the participants IIM 5. Has experienced myocardial infarction (MI), unstable ischemic heart disease, or stroke within 12 weeks of screening |
| Recruitment start date | 30/05/2023 |
| Recruitment end date | 27/02/2025 |
Locations
Countries of recruitment
- Australia
- Canada
- England
- France
- Germany
- Hungary
- Italy
- Japan
- Mexico
- Netherlands
- Poland
- Spain
- United Kingdom
Study participating centres
London
NW1 2PQ
United Kingdom
Eccles
Salford
M6 8HD
United Kingdom
Sponsor information
Industry
Archimedesweg 29
Leiden
2333
Netherlands
| Phone | +31 (0)71 524 2166 |
|---|---|
| ClinicalTrialsEU@its.jnj.com |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 10/05/2028 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | 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 the 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 & 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. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
05/06/2023: Internal review.
03/12/2022: ISRCTN received notification of combined HRA/MHRA approval for this trial on 03/12/2022.
21/09/2022: Trial's existence confirmed by the HRA.
