| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10059142 |
| E.1.2 | Term | Sjoegren's syndrome |
| E.1.2 | System Organ Class | 100000004859 |
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| 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 |
Population #1:
To evaluate the clinical efficacy of multiple doses of VIB4920 in glandular and extraglandular manifestations of SS patients with moderate to high systemic disease activity.
Population #2:
To evaluate the clinical efficacy of multiple doses of VIB4920 in the key subjective complaints of SS (dryness, fatigue and pain). |
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| E.2.2 | Secondary objectives of the trial |
Population #1:
1. To evaluate the effect of VIB4920 on systemic activity and patient-reported outcomes in subjects with SS.
2. To evaluate the safety and tolerability of multiple doses of VIB4920 in subjects with SS.
3. To characterize the PK of VIB4920 in subjects with SS.
4. To assess the immunogenicity of VIB4920 in subjects with SS.
Population #2:
1. To evaluate the effect of VIB4920 on patient-reported outcomes in subjects with SS.
2. To evaluate the safety and tolerability of multiple doses of VIB4920 in subjects with SS.
3. To characterize the PK of VIB4920 in subjects with SS.
4. To assess the immunogenicity of VIB4920 in subjects with SS. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Population #1:
1. Adults, 18 years or older at time of informed consent ( the minimum age for adult participants can be higher than 18 years in countries with different regulations).
2. Diagnosed with SS by meeting the 2016 ACR/EULAR Classification Criteria.
3. Have an ESSDAI score of ≥ 5 at screening; the following domains will be scored but they will not contribute to the minimum ESSDAI score of 5 required for inclusion: Peripheral nervous system, Central nervous system, and Pulmonary.
4. Positive for either anti-Ro autoantibodies or RF, or both at screening.
5. Written informed consent and any locally required authorization obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations.
6. Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception from signing the informed consent form (ICF), and must agree to continue using such precautions through the end of the study follow-up; cessation of contraception after this point should be discussed with a responsible physician. A recommendation that the female partners (of childbearing potential) of male study participants should use a highly effective method of contraception other than a barrier method is made.
7. Nonsterilized male subjects who are sexually active with a female partner of childbearing potential must use a condom with spermicide from Day 1 through the end of the study.
8. Meets all of the following tuberculosis (TB) criteria:
a. No history of latent or active TB prior to screening, with the exception of latent TB with documented completion of appropriate treatment.
b. No signs or symptoms suggestive of active TB from medical history or physical examination.
c. No recent (≤ 12 weeks of screening) close contact with a person with active TB.
d. Negative Interferon Gamma Release Assay (IGRA) test result for TB obtained within 12 weeks prior to randomization. Subjects with an indeterminate test result can repeat the test, but if the repeat test is also indeterminate, they are excluded.
e. A chest radiograph (obtained during the screening period or any time within 12 weeks prior to signing of the ICF) with no evidence of current active TB or other infection, or old active TB, malignancy, or clinically significant abnormalities suggesting an active process (unless due to SS).
Population #2:
1. Male or female adults, 18 years old or older at time of informed consent.
2. Diagnosed with SS by meeting the 2016 ACR/EULAR Classification Criteria.
3. Have an ESSPRI score of ≥ 5 at screening.
4. Have an ESSDAI score of < 5 at screening.
5. Positive for either anti-Ro autoantibodies or RF, or both at screening.
6. Residual salivary gland function as defined by whole stimulated salivary flow > 0.1 mL/min.
7. Written informed consent and any locally required obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations.
8. Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception from signing the ICF, and must agree to continue using such precautions through the end of the follow up of the study; cessation of contraception after this point should be discussed with a responsible physician. A recommendation that the female partners (of child bearing potential) of male study participants should use a highly effective method of contraception other than a barrier method will be made.
9. Nonsterilized male subjects who are sexually active with a female partner of childbearing potential must use a condom with spermicide from Day 1 through to the end of the study.
10. Meets all of the following TB criteria:
a. No history of latent or active TB prior to screening, with the exception of latent TB with documented completion of appropriate treatment.
b. No signs or symptoms suggestive of active TB from medical history or physical examination.
c. No recent (≤ 12 weeks of screening) close contact with a person with active TB.
d. Negative IGRA test result for TB obtained within 12 weeks prior to randomization.
e. A chest radiograph (obtained during the screening period or anytime within 12 weeks prior to signing of the ICF) with no evidence of current active TB or other infection, or old active TB, malignancy, or clinically significant abnormalities suggesting an active process (unless due to SS). |
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| E.4 | Principal exclusion criteria |
Populations #1 and #2:
1. Patients with medical history of confirmed deep venous thrombosis or arterial thromboembolism within 2 years of signing the ICF.
2. Patients with risk factors for venous thromboembolism or arterial thrombosis, prothrombotic status.
3. Patients requiring treatment with anticoagulant drugs.
4. Concomitant polymyositis or dermatomyositis or systemic sclerosis.
5. Active malignancy or history of malignancy, except as follows:
a. In situ carcinoma of the cervix treated with apparent success with curative therapy > 12 months prior to screening; or
b. Cutaneous basal cell carcinoma following apparently curative therapy.
6. Subjects who are pregnant or lactating or planning to become pregnant during the duration of the study.
7. Subjects who have a positive test for, or have been treated for hepatitis B, hepatitis C, or HIV infection.
8. Subjects with:
a. a history of more than one episode of herpes zoster and/or opportunistic infection in the last 12 months, with the exception of oral candidiasis, vaginal candidiasis, and cutaneous fungal infections.
b. Active viral, bacterial or other infections requiring systemic treatment at the time of screening or through randomization, or history of more than 2 infections requiring IV antibiotics within 12 months prior to signing the ICF.
c. Epidemiologic risk of COVID-19 ( recent exposure, high-risk housing) and for health-related risk of COVID-19 severity based on current understanding of risk factors for severe disease when making a decision regarding the individual subject's risk of participation. Subject who have active COVID-19 infection or disease or other significant infection, or, in the judgment of the investigator, who may be at unacceptable risk of COVID-19 or its complications should not be randomized.
d. A documented positive SARS-CoV-2 test within 2 weeks prior to randomization. Subject with a positive test for SARS-CoV-2 may be rescreened at least 2 weeks after a positive test if asymptomatic and at least 3 weeks after symptomatic COVID-19 illness.
9. Subjects with known history of severe allergy or reaction to any component of the IP formulation or to any other biologic therapy.
10. Subjects with any severe cardiovascular, respiratory, endocrine, gastrointestinal, hematological, neurological, psychiatric, or systemic disorder or any other condition that in the opinion of the Investigator, would place the subject at unacceptable risk of complications, interfere with evaluation of the IP or confound the interpretation of subject safety or study results.
11. Subjects who are unable or unwilling to comply with protocol requirements.
12. Subjects who have received live vaccine within the 4 weeks prior to ICF signature.
13. Last administration of experimental biologic or oral agents < 3 months or 5 half-lives before randomization.
14. Subjects who have had previous treatment with any biologic B-cell-depleting therapy within 12 months or other B-cell targeting therapy < 3 months before randomization.
15. Use of the following medications:
- Antimalarials if they have been initiated or if the dose has changed within 8 weeks prior to signing the ICF or during the screening period.
- Any medication that, in the opinion of the Investigator, would interfere with evaluation of the IP or interpretation of subject safety or study
results.
- Any increase or initiation of new doses of cevimeline or pilocarpine and cyclosporine eye drops (Restasis ®) within 2 weeks prior to signing the
ICF through randomization (Day 1).
Please refer to the protocol for details of additional prohibited medications for Population #1 and for Population #2.
16. Subjects who have received previous treatment with anti-CD40L compounds at any time before screening.
17. Subjects with blood tests, at screening, of any of the following:
• AST > 2 x ULN
• ALT > 2 x ULN
• TBL > 2 x ULN
• Hemoglobin < 75 g/L
• Neutrophils < 1.0 x 109/L
• Platelets < 100 x 109/L
• Prothrombin or PTT > ULN
Additional exclusion criteria for Population #1:
1. Injectable corticosteroids (including intra-articular) or treatment with > 10 mg/day dose oral prednisone or equivalent within 6 weeks prior to randomization.
2. Subjects treated with systemic corticosteroids for indications other than SS for more than a total of 2 weeks within 24 weeks prior to ICF signature.
3. Use of any of the medications specified in the protocol.
Additional exclusion criteria for Population #2:
1. Use of the any of the medications specified in the protocol. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Population #1:
Change from baseline in ESSDAI at Day 169.
Population #2:
Change from baseline in ESSPRI at Day 169. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Population #1:
1. Change from baseline in ESSPRI at Day 169.
2. Proportion of subjects achieving ESSDAI[3] and ESSDAI[4] response, defined as a decrease of at least 3[4] points from baseline in the ESSDAI at Day 169 without premature discontinuation from the study and without receiving rescue therapy.
3. Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score at Day 169.
4. Change from baseline in Ocular Surface Disease Index (OSDI©) at Day 169.
5. Patient’s Global Impression of Severity (PGIS) at Day 169.
6. Safety and tolerability of multiple IV doses of VIB4920 as measured by the incidence of TEAEs, treatment-emergent serious adverse events (TESAEs), adverse events of special interest (AESIs), and laboratory, vital sign, and electrocardiogram (ECG) abnormalities.
7. PK during the study.
8. Proportion of subjects with positive immunogenic response measured by anti-VIB4920 antibodies until the completion of the study.
Population #2:
1. Proportion of subjects achieving ESSPRI response, defined as ≥ 1 point or 15% reduction from baseline in ESSPRI score at Day 169 without premature discontinuation from the study and without receiving rescue therapy.
2. Change from baseline in FACIT-Fatigue score at Day 169.
3. Change from baseline in OSDI at Day 169.
4. Patient’s Global Impression of Severity at Day 169
5. Safety and tolerability of multiple IV doses of VIB4920 as measured by the incidence of TEAEs, TESAEs, AESIs, and laboratory, vital sign, and ECG abnormalities.
6. PK during the study.
7. Proportion of subjects with positive immunogenic response measured by anti-VIB4920 antibodies until the completion of the study. |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
ESSPRI, ESSDAI, FACIT-Fatigue, OSDI - Baseline and Day 169
PGIS - Day 169
Safety - all study visits from throughout study
PK - all study visits from Day 1 throughout study
Immunogenic response - Days 1, 29, 85, 169, 197, 253, 309 and 365
|
|
| 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 | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Tolerability, immunogenicity, biomarker analysis |
|
| 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 | 2 |
| 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 25 |
| 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 |
| Argentina |
| India |
| Korea, Republic of |
| Mexico |
| Peru |
| Taiwan |
| United States |
| France |
| Hungary |
| Italy |
| Poland |
| United Kingdom |
|
| 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
|
| The study will be completed once the last subject out has completed all Visit 15 or early discontunuation assessments. |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 12 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 16 |
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