Evaluation of Dazodalibep Efficacy and Safety in Patients with Moderate-to-Severe Sjögren’s Syndrome: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study
- Trial ID
- 2023-503923-24-00
- Protocol
- HZNP-DAZ-303
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the effect of **dazodalibep** on patient-reported symptoms in participants with Sjögren’s Syndrome (SS) who exhibit a moderate-to-severe symptom state. This is clinically relevant as it aims to assess the potential of dazodalibep to alleviate the symptomatic burden experienced by patients with this autoimmune condition, thereby improving their quality of life.
Secondary objectives include:
- Evaluating the effect of dazodalibep on measures of patient-reported outcomes (PROs) in participants with SS.
- Assessing the impact of dazodalibep on systemic activity, PROs, and salivary flow in participants with SS.
- Evaluating the safety and tolerability of multiple doses of dazodalibep in participants with SS.
Participants
The clinical trial involves a total of **275 participants** diagnosed with **Sjögren’s Syndrome** with a moderate-to-severe symptom state. The study population includes both male and female adults aged 18 years and older, with the age range categories specified as 3 and 4. Participants were selected based on specific inclusion criteria, including a diagnosis according to the 2016 American College of Rheumatology/EULAR Classification Criteria and the presence of certain autoantibodies. The trial population is characterized by a requirement for residual salivary gland function and vaccination against SARS-CoV-2, among other health considerations. Lifestyle factors such as diet and physical activity are not specified, but participants must adhere to contraceptive guidelines if applicable. The trial does not exclude vulnerable populations, indicating a broad inclusion strategy within the defined criteria.
Plans and Procedures
The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the efficacy and safety of **Dazodalibep** in participants with **Sjögren's Syndrome** with moderate-to-severe symptom state. The trial is structured to include a series of study visits, beginning with an inclusion (screening) visit, followed by regular follow-up visits, and concluding with an end-of-study visit. The trial is expected to span a total duration of approximately four years, with an estimated recruitment start date in July 2024 and an anticipated end date in June 2028.
Participants will be involved in the study for a maximum treatment period of 309 days. The inclusion visit will assess eligibility based on criteria such as age, diagnosis, and symptom severity. Participants must be adults diagnosed with Sjögren's Syndrome according to the 2016 American College of Rheumatology/EULAR Classification Criteria, with specific symptom scores and antibody positivity confirmed by a central lab. Follow-up visits will monitor the primary endpoint, which is the change from baseline in the ESSPRI score at Week 48, along with secondary endpoints including changes in various symptom scores and the incidence of treatment-emergent adverse events.
Participants will receive either Dazodalibep or a placebo, both administered as a solution for infusion. The study will maintain a double-blind design to ensure unbiased results. Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or the occurrence of adverse events that necessitate discontinuation. The trial aims to provide comprehensive data on the therapeutic potential of Dazodalibep in managing symptoms of Sjögren's Syndrome, contributing valuable insights into its safety and efficacy profile.
Treatment
The clinical trial involves the administration of **Dazodalibep**, a **biological** agent formulated as a **solution for infusion**. Dazodalibep is an active substance known as a human tenascin third fibronectin type III domain binding to human CD40 ligand and fused to human albumin. It is also referred to by its synonyms, including MEDI4920 and VIB4920. The pharmaceutical form is a solution intended for intravenous infusion. The maximum daily dose is 63 mg, with a total maximum dose of 19,500 mg over a treatment period of 309 days. The administration schedule and participant compliance are monitored to ensure adherence to the dosing regimen.
The study also includes a **placebo** control, which is formulated as a sterile liquid for intravenous infusion following dilution in normal saline. Each vial contains a nominal volume of 5.0 mL. The placebo is aseptically filled into 6R glass vials, stoppered with a Flurotec-coated elastomeric stopper, and sealed with an aluminum overseal. The placebo serves as a comparator to evaluate the efficacy and safety of Dazodalibep in participants with Sjögren’s Syndrome with moderate-to-severe symptom state. The administration of the placebo follows the same route and frequency as the experimental medication to maintain the study's double-blind design.
Efficacy
The efficacy of Dazodalibep in the treatment of **Sjögren’s Syndrome** with moderate-to-severe symptom state will be assessed through a series of primary and secondary endpoints. The primary endpoints include the change from baseline in the DASPRI score and the ESSPRI score at Week 48. These scores are patient-reported outcomes that measure symptom severity and impact on daily life.
Secondary endpoints will further evaluate the efficacy by examining the proportion of participants achieving a meaningful improvement in the DASPRI or ESSPRI response, defined as a decrease of at least 1.5 points from baseline in the ESSPRI score, without premature discontinuation from treatment and without receiving rescue or potentially confounding therapy. Additional secondary endpoints include changes from baseline in DASPRI Dryness or ESSPRI Dryness, PROMIS-Fatigue SF-10a, DASPRI Pain or ESSPRI Pain, and the 36-item Short Form Survey (SF-36) Physical Component Summary score at Week 48. Changes in total stimulated salivary flow at Week 48 will also be assessed.
The efficacy parameters will be measured at specific timepoints, including Week 12, Week 24, and Week 48, using validated scales and patient-reported outcomes. The analysis will focus on the changes from baseline in these scores to determine the impact of Dazodalibep on the symptoms of Sjögren’s Syndrome. The study will also monitor the incidence of treatment-emergent adverse events, treatment-emergent serious adverse events, and adverse events of special interest to ensure a comprehensive evaluation of both efficacy and safety.
Inclusion and Exclusion Criteria
Inclusion Criteria
- (1-5) "1. Adults, ≥ 18 years at time of informed consent (the minimum age for adult participants may be greater than 18 years of age in accordance with country-specific age definitions for adulthood). Participants must be capable of providing their own informed consent. 2. Diagnosed with SS by meeting the 2016 American College of Rheumatology (ACR)/EULAR Classification Criteria (Section 10.1, Appendix 1). If SS diagnosis is based on positive anti-Ro autoantibody, anti-Ro positivity must be confirmed by central lab. 3. Have an ESSPRI score of ≥ 5 at screening despite current or prior symptomatic or local therapy. 4. Have an ESSDAI score of < 5 at screening. 5. Positive for either anti-Ro autoantibodies or rheumatoid factor (RF), or both at screening (as per the definition of the standard central laboratory test). "
- (6-7)"6. Residual salivary gland function as defined by whole stimulated salivary flow > 0.1 mL/min. 7. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the [US, EU] General Data Protection Regulation [GDPR] in the EU) obtained from the participant prior to performing any protocol-related procedures, including screening evaluations. Participants must be able to self-complete Patient-Reported Outcomes (PROs) without assistance.
- " 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 informed consent form (ICF) and must agree to continue using such precautions through the end of the study or 3 months after last IP administration (if participant withdraws from study). Cessation of contraception after this point should be discussed with a responsible physician. The Investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of IP. A woman of childbearing potential must have a negative highly sensitive serum pregnancy test at screening and must have a negative urine pregnancy test on the day of dosing prior to each dose of IP (Section 8.3.5). Additional requirements for pregnancy testing during and after study intervention are located in Section 8.3.5. The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. Highly effective methods of contraception (with a failure rate of < 1% per year when used consistently and correctly) include: · Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: - Oral - Intravaginal - Transdermal - Injectable · Progestogen-only hormonal contraception associated with inhibition of ovulation: - Oral - Injectable - Implantable · Intrauterine device (IUD) · Intrauterine hormone-releasing system (IUS) · Bilateral tubal occlusion · Vasectomized partner if partner is the sole sexual partner of the female subject of childbearing potential and that the vasectomized partner has received medical assessment of the surgical success). · Sexual abstinence Sexual abstinence is considered a highly effective method only if it is the preferred and usual lifestyle of the participant and the participant agrees to refrain from heterosexual intercourse from screening through the end of the study follow-up. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. 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 should be made. - Females of childbearing potential are defined as those who are not surgically sterile (surgical sterilization includes bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) or those who are not postmenopausal (defined as 12 - consecutive months with no menses without an alternative medical cause). - Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the woman of childbearing potential study participant and that the vasectomized partner has received medical assessment of the surgical success.
- (10) "10. Meets all of the following tuberculosis (TB) criteria: a. No history of latent or active TB prior to screening, except for latent TB with documented completion of locally 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 (close contact is defined as ≥ 4 hours/week OR living in the same household OR in a house where a person with active TB is a frequent visitor). d. Negative Interferon Gamma Release Assay (IGRA) test result for TB at screen unless previously treated as per Inclusion Criterion 11(a). Participants with an indeterminate test result can repeat the test, but if the repeat test is also indeterminate, they are excluded. If IGRA result by central laboratory is incongruent with recent local testing within 4 weeks prior to or during screening, a repeat assessment will be permitted. e. A chest radiograph (obtained during the screening period or any time within 12 weeks prior to screening) with no evidence of current active TB or other infection, or prior TB, malignancy, or clinically significant abnormalities suggesting an active process (unless due to SS)."
Exclusion Criteria
- (1-5) "1. Individuals with medical history of confirmed deep venous thrombosis, pulmonary embolism, or arterial thromboembolism within 2 years of screening. 2. History or presence of concomitant polymyositis or dermatomyositis or systemic sclerosis. 3. Active malignancy or history of malignancy within the last 5 years, 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 presumed curative therapy. 4. Individuals who are pregnant or lactating or planning to become pregnant or donate eggs during the study or for 3 months after the last dose of IP (if participant withdraws from study). 5. Individuals who have a positive test for, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection. A positive test for hepatitis B at screening is defined as: (1) positive for hepatitis B surface antigen (HBsAg); OR (2) positive for hepatitis B core antibody (HBcAb) or hepatitis B surface antibody (HBsAb) AND hepatitis B virus (HBV) DNA detected above the lower limit of quantification (LLOQ) by reflex testing by the central laboratory at screening. Individuals with a positive test for or a history of treatment for hepatitis C are excluded unless they have a documented sustained viral response to antiviral drugs approved for the treatment of hepatitis C, defined as an undetectable viral level of hepatitis C RNA at least 24 weeks following completion of therapy. Individuals with advanced fibrosis or cirrhosis due to hepatitis C should not be enrolled. "
- (6-13) "6. Individuals with a positive test for SARS-CoV-2 on the day of randomization. Only those with symptoms suggestive of SARS-CoV-2 at randomization or significant exposure to (COVID-19) within 10 days prior to randomization, should be tested. Individuals with COVID-19 or COVID-19 exposure can delay randomization for 10 days and randomize once recovered; otherwise, they will need to rescreen. 7. Individuals with: a. Any opportunistic infections in the last 12 months (Section 10.3, Appendix 3), with the exception of a single episode of herpes zoster, non-invasive herpes simplex at any site, oral candidiasis, vaginal candidiasis, or cutaneous fungal infections, which are permitted within the prior 12 months unless of unusual severity. b. Active 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 screening. 8. Individuals with known history of severe allergy or reaction to any component of the IP formulation or to any other biologic therapy. 9. Individuals with any severe or life-threatening cardiovascular (including vasculitis), respiratory, endocrine, gastrointestinal, hematological, neurological, psychiatric, or systemic disorder or any other condition that, in the opinion of the Investigator, would place the individual at unacceptable risk of complications, interfere with evaluation of the IP, or confound the interpretation of participant safety or study results. 10. Individuals who, in the opinion of the Investigator, are unable or unwilling to comply with protocol requirements (eg, active drug or alcohol abuse or for other reasons), including the completion of the DASPRI and PRO. 11. Individuals who have received live (attenuated) vaccine within the 4 weeks prior to randomization or plan to receive a live vaccine during their participation in the study. Non-live vaccines are permitted during study (see Inclusion Criterion 10 for COVID-19 vaccination); however, for participants planning to receive a vaccine within a month after Dose 1, completing vaccination prior to starting dosing should be considered by the Investigator. 12. Last administration of experimental or investigational biologic or oral agents (other than those listed in Exclusion Criterion 15) < 6 months prior to screening. 13. Individuals who have had previous treatment with any biologic B-cell-depleting therapy (eg, rituximab, ocrelizumab, inebilizumab, ofatumumab, or ianalumab) within 12 months or other B-cell-targeting therapy (eg, belimumab) < 3 months prior to screening."
- (14-17) "14. Individuals treated with systemic corticosteroids for indications other than SS, RA, and SLE for more than a total of 2 weeks within 6 months prior to screening. 15. Use of the following medications: a. Antimalarials (eg, chloroquine, hydroxychloroquine, quinacrine) if they have been initiated or if the dose has changed within 8 weeks prior to screening or during the screening period. b. Oral, intramuscular, (IM), IV, or intra-articular (IA) corticosteroids within 4 weeks prior to screening. Pro re nata (PRN) use of oral corticosteroids is not allowed during the screening window and through randomization. Inhaled, intranasal, or topical corticosteroids are allowed provided doses are expected to be stable during the study. c. Methotrexate, azathioprine, leflunomide, mycophenolate mofetil (MMF), other disease-modifying anti-rheumatic drug (DMARD), immunosuppressant, immunosuppressive biologics, or antiproliferative agents if last dose was taken within: 4 weeks prior to screening; OR Drug-specific 5 half-lives elimination period (if longer than 4 weeks). d. Any medication that, in the opinion of the Investigator, would interfere with evaluation of the IP or interpretation of participant safety or study results. e. Any increase or initiation of a new dose of regularly scheduled nonsteroidal anti-inflammatory drugs within 2 weeks prior to screening through randomization (Day 1). f. Any increase or initiation of new doses of cevimeline, pilocarpine, or cyclosporine eye drops (Restasis®) or lifitegrast (Xiidra®) or any other topical (ophthalmic) anti-inflammatory/ immunomodulatory eyedrops within 2 weeks prior to screening through randomization (Day 1). g. Use of herbal or homeopathic remedies for underlying rheumatological conditions, specifically sinomenine, tripterygium glycosides, or total glucosides of peony, within 4 weeks prior to screening. 16. Individuals who have received previous treatment with anti-CD40L compounds at any time before screening. 17. Individuals with blood tests, at screening, of any of the following: Aspartate aminotransferase (AST) > 2 × upper limit of normal (ULN). Alanine aminotransferase (ALT) > 2 × ULN. Total bilirubin (TBL) > 2 × ULN, unless Gilbert’s syndrome is documented in the medical history. Hemoglobin < 90 g/L. Neutrophils < 1.0 × 109/L. Lymphocytes < 0.5 × 109/L. Platelets < 100 × 109/L. International normalized ratio (INR) > 1.3"
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 01 Jul 2024 | 3 |
 Croatia | Not Recruiting | 01 Jul 2024 | 13 |
 Denmark | Not Recruiting | 01 Jul 2024 | 9 |
 France | Not Recruiting | 01 Jul 2024 | 9 |
 Germany | Not Recruiting | 01 Jul 2024 | 13 |
 Greece | Not Recruiting | 01 Jul 2024 | 8 |
 Hungary | Not Recruiting | 01 Jul 2024 | 8 |
 Italy | Not Recruiting | 01 Jul 2024 | 13 |
 Poland | Not Recruiting | 01 Jul 2024 | 80 |
 Portugal | Not Recruiting | 01 Jul 2024 | 9 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Dazodalibep | Test | SOLUTION FOR INFUSION | SOLUTION FOR INFUSION | 9999 | 9999 | PRD10299897 |
The placebo is formulated as sterile liquid intended for intravenous infusion following dilution in normal saline. The nominal volume in each vial is 5.0 mL. The placebo is aseptically filled into 6R glass vials, stoppered with a Flurotec-coated elastomeric stopper, and sealed with an aluminum overseal. | Placebo | N/A | — | — | — | N/A |