E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Sjogren's Syndrome |
|
E.1.1.1 | Medical condition in easily understood language |
Primary Sjogren's Syndrome |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040766 |
E.1.2 | Term | Sjogren's disease |
E.1.2 | System Organ Class | 100000004859 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of nipocalimab in participants with primary Sjogren’s syndrome
(pSS) versus placebo
|
|
E.2.2 | Secondary objectives of the trial |
- To evaluate the safety of nipocalimab
treatment versus placebo in participants with
pSS
- To evaluate the pharmacokinetics (PK) and
immunogenicity of nipocalimab in
participants with pSS
- To evaluate the effect of nipocalimab versus
placebo on levels of serum biomarkers related
to pSS |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
optional labial salivary gland biopsy substudy |
|
E.3 | Principal inclusion criteria |
- Meets classification criteria for primary sjogren's syndrome (pSS) by the 2016 American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) within 5 years but at least 6 months prior to screening
- At screening is seropositive for antibodies to pSS-associated antigen A (60 kilodalton [kDa] Ro/sjogren's syndrome-related antigen [SSA])
- Total Clinical European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (clinESSDAI) score greater than or equal to (>=) 6 and less than or equal to (<=) 13
- At least low activity as defined in the biological domain of European League Against Rheumatism (EULAR) and in at least low activity in at least one of the following ESSDAI domains: cutaneous, articular, glandular, constitutional, hematologic, and lymphadenopathy
- It is recommended that participants are up to date on all age-appropriate vaccinations prior to screening as per routine local medical guidelines. For study participants who received locally-approved (and including emergency use-authorized) coronavirus disease 2019 (COVID-19) vaccines recently prior to study entry, applicable local vaccine labelling, guidelines, and standards-of-care for participants receiving immune-targeted therapy will be followed when determining an appropriate interval between vaccination and study enrollment. |
|
E.4 | Principal exclusion criteria |
-Has any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her pSS or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant
- Comorbidities (for example, asthma, chronic obstructive pulmonary disease) which have required 3 or more courses of systemic glucocorticoids within the previous 12 months
- Has any unstable or progressive manifestation of pSS that is likely to warrant escalation in therapy beyond permitted background medications and/or has severely active pSS (clinESSDAI score greater than [>] 13)
- Has received oral cyclophosphamide within 3 months or intravenous (IV) cyclophosphamide within 6 months prior to first administration of study intervention
- Has sjogren's syndrome overlap syndromes where another confirmed autoimmune rheumatic or systemic inflammatory condition (for example, rheumatoid arthritis [RA], systemic lupus erythematosus [SLE], scleroderma, inflammatory bowel disease [IBD]) is the primary diagnosis or has clinical manifestations that, in the opinion of the investigator, are likely to interfere with the investigator's ability to assess pSS manifestations |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in Clinical European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (clinESSDAI) score at Week 24 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Change from baseline in EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) score at Week 24
2. Improvement of ≥4 points from baseline in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score (minimal clinically important improvement) at Week 24
3. Improvement of ≥4 points from baseline in clinESSDAI score (minimal clinically important improvement) at Week 24
4. ESSPRI response defined as a decrease of one point or a decrease of ≥15% from baseline
(minimal clinically important improvement) at Week 24
5. Sjogren's Syndrome Responder Index (SSRI) response defined as ≥20% improvement from
baseline in at least two of five domains (fatigue, oral dryness, ocular dryness, unstimulated whole salivary flow, erythrocyte sedimentation rate) at Week 24
6. Improvement in disease activity level by ≥1 level in at least one clinESSDAI or ESSDAI domain (biological, hematological, cutaneous, constitutional, lymphadenopathy and lymphoma, and glandular) at Week 24 - Improvement from baseline in ≥3 of 5 composite of relevant endpoints for Sjogren’s Syndrome (CRESS) categories at Week 24
7. Percentage of Participants with Treatment-emergent Adverse Events (TEAEs)
8. Percentage of Participants with Adverse Events of Special interests (AESIs)
9. Percentage of Participants with Treatment-emergent Serious Adverse Events (SAEs)
10. Percentage of Participants with Clinically Significant Abnormalities in Vital Signs
11. Percentage of Participants with Clinically Significant Abnormalities in Laboratory Parameters
12. Serum Concentration of Nipocalimab Over Time
13. Number of Participants with Antibodies to Nipocalimab (Anti-drug Antibodies [ADAs] and Neutralizing Antibodies [NAbs])
14. Number of Participants with Change from Baseline in Biomarkers
15. Number of Participants with Change from Baseline in Autoantibodies
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
secondary endpoint 1-7 at week 24
secondary endpoint 8-12, up to week 36
secondary endpoint 13 at week 30
secondary endpoint 14-16 up t week 36 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Germany |
Italy |
Japan |
Netherlands |
Poland |
Portugal |
Spain |
Taiwan |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
last follow-up assessment (8 weeks after the last infusion of study intervention) for the last participant. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |