Primary Sjögren's Syndrome, Systemic Lupus Erythematosus
Conditions
Keywords
systemic lupus erythematosus, primary Sjögren's syndrome, SLE, pSS
Brief summary
This study consists of a randomized, double-blind, placebo-controlled Phase Ia part and an open-label Phase Ib part. The Phase Ia part is a single ascending-dose study of subcutaneous QLS2404 Injection in healthy participants, designed to evaluate the safety and tolerability of QLS2404 Injection in healthy participants. The Phase Ib part is a multiple ascending-dose study of subcutaneous QLS2404 Injection in participants with systemic lupus erythematosus and primary Sjögren's syndrome, designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of QLS2404 Injection.
Detailed description
The Phase Ia single-dose ascending stage will include five dose groups. The study plans to enroll 40 adult healthy participants, with 8 participants in each dose group, who will be randomized in a 3:1 ratio to receive QLS2404 Injection or placebo. Dose escalation will be conducted sequentially from the initial dose to higher dose levels in accordance with the dose-escalation principle. During the study, a Safety Monitoring Committee (SMC), composed of the investigators, the sponsor, or sponsor-designated personnel, will review the safety data generated during the trial. After the last participant in each dose group has completed the 14-day tolerability observation period following dosing, the SMC will review the safety data of participants in each cohort and conduct an integrated assessment of the available pharmacokinetic (PK) and pharmacodynamic (PD) data. The SMC will then provide recommendations regarding dose escalation or, if necessary, adjustments to the dose-escalation scheme. The Phase Ib part will be a multiple ascending-dose study of subcutaneous QLS2404 Injection in participants with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS), designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of QLS2404 Injection. Three dose groups are planned, with approximately 24 participants to be enrolled in total and 8 participants in each dose group. All participants will receive three subcutaneous doses of QLS2404 Injection, administered at 4-week intervals. Each dose group must include at least 6 participants with SLE, and the study will be conducted in strict accordance with the dose-escalation principle.
Interventions
DRUGIb:QLS2404 high dose
multiple subcutaneous doses of QLS2404 Injection in participants with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS)
DRUGIb:QLS2404 middle dose
multiple subcutaneous doses of QLS2404 Injection in participants with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS)
DRUGIa:QLS2404 very low dose
a single subcutaneous dose of QLS2404 Injection in healthy participants
DRUGIa:QLS2404 low dose
a single subcutaneous dose of QLS2404 Injection in healthy participants
DRUGIa:QLS2404 middle dose
a single subcutaneous dose of QLS2404 Injection in healthy participants
DRUGIa:QLS2404 high dose
a single subcutaneous dose of QLS2404 Injection in healthy participants
DRUGIa:QLS2404 Max dose
a single subcutaneous dose of QLS2404 Injection in healthy participants
DRUGIb:QLS2404 low dose
multiple subcutaneous doses of QLS2404 Injection in participants with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS)
Sponsors
Qilu Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Ia * Participants who understand and comply with the study procedures and methods, voluntarily participate in this trial, provide written informed consent, and are able to complete the study in accordance with the protocol requirements. * Male or female participants aged ≥18 and ≤45 years on the date of signing the informed consent form. * Body mass index (BMI) at screening ≥19 kg/m² and ≤26 kg/m², with body weight ≥45 kg. * Participants assessed by the investigator to be in good health based on medical history, physical examination, vital signs, and laboratory test results during the screening period. * Ib * Participants who voluntarily sign the informed consent form before the initiation of any study-related procedures, are able to communicate effectively with the investigator, understand and are willing to strictly comply with the requirements of this clinical study protocol, and complete the study. * Male or female participants aged ≥18 and ≤65 years at the time of signing the informed consent form. * Body mass index (BMI) at screening ≥18 kg/m² and ≤35 kg/m². * Participants with systemic lupus erythematosus must meet the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for SLE and be diagnosed with systemic lupus erythematosus; the diagnosis must have been established at least 6 months prior to signing the informed consent form. * Participants with primary Sjögren's syndrome must meet the 2016 ACR/EULAR classification criteria for primary Sjögren's syndrome and be diagnosed with primary Sjögren's syndrome; the diagnosis must have been established at least * months prior to signing the informed consent form.
Exclusion criteria
* Ia * QTcF interval corrected by electrocardiogram (ECG) ≥450 ms at screening; and any other ECG abnormalities that, in the investigator's opinion, may pose an unacceptable risk to the participant. * Participants with a history of, or current, chronic or serious diseases of the musculoskeletal, neuropsychiatric, endocrine, circulatory, respiratory, digestive, urinary, reproductive, or other systems, who are considered by the investigator to be unsuitable for participation in the clinical trial. * Participants who have lost more than 400 mL of blood due to blood donation or other reasons within 3 months prior to screening. * Participants who are considered by the investigator to be unsuitable for participation in the clinical trial or unable to complete this study for other reasons. * Ib * Any disease or condition that, in the investigator's opinion, may interfere with the evaluation of study drug efficacy, participant safety assessment, or interpretation of study results. * Participants who have participated in any cell therapy, gene therapy clinical trial, or medical device clinical trial within 3 months prior to screening. * Participants who have received Bacillus Calmette-Guérin (BCG) vaccination within 1 year prior to screening. * Participants who have received any live attenuated vaccine within 1 month prior to screening or who require live attenuated vaccination during study participation. * Participants who are breastfeeding or have a positive serum human chorionic gonadotropin (hCG) test during the screening period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ia:the safety and tolerability of a single subcutaneous dose of QLS2404 Injection in healthy participants | from the first single subcutaneous Inject of QLS2404 up to Day85 | Number of participants with Adverse events and Serious adverse events |
| Ib:To evaluate the Adverse events of multiple subcutaneous injections of QLS2404 Injection in participants with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). | from the first single subcutaneous Inject of QLS2404 up to Day141. | Number of participants with Adverse events and Serious adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ia Outcome 1:To evaluate the pharmacokinetic (PK) characteristics of a single subcutaneous injection of QLS2404 Injection in healthy participants. | from the first single subcutaneous Inject of QLS2404 up to Day85 | include serum QLS2404 concentrations such as peak plasma concentration (Cmax) |
| Ia Outcome 2:To evaluate the pharmacodynamic (PD) characteristics of a single subcutaneous injection of QLS2404 Injection in healthy participants. | from the first single subcutaneous Inject of QLS2404 up to Day85. | assessments include serum levels of IgM, IgG, and IgA at each scheduled time point before and after dosing |
| Ia Outcome 3:To evaluate the immunogenicity of a single subcutaneous injection of QLS2404 Injection in healthy participants. | from the first single subcutaneous Inject of QLS2404 up to Day85 | include the incidence and titers of anti-drug antibodies (ADAs) against QLS2404 Injection in healthy participants, and the incidence of neutralizing antibodies (NAbs), if data permit. |
| Ib Outcome 1:Applicable to participants with SLE: The proportion of participants with a ≥ 4-point decrease from baseline in SLE Disease Activity Index 2000 (SLEDAI-2K). | from the first subcutaneous Inject of QLS2404 up to Day141. | SLEDAI-2K Description: The minimum SLEDAI-2K score is 0, and the maximum theoretical SLEDAI-2K score is 105. A score of 0 indicates no active disease; a greater score indicates higher systemic lupus erythematosus disease activity. |
| Ib Outcome 2:To evaluate the pharmacokinetic (PK) characteristics of multiple subcutaneous injections of QLS2404 Injection in participants . | from the first subcutaneous Inject of QLS2404 up to Day141 | Serum drug concentrations after administration peak plasma concentration (Cmax) |
| Ib Outcome 3:Evaluate the PD characteristics of multiple subcutaneous injections of QLS2404 Injection in participants with SLE and pSS; | from the first subcutaneous Inject of QLS2404 up to Day141 | Serum IgM, IgG, and IgA levels at each assessment time point, and the percentage change from baseline; |
| Ib Outcome 4:Evaluate the immunogenicity of multiple subcutaneous injections of QLS2404 Injection in participants with SLE and pSS; | from the first subcutaneous Inject of QLS2404 up to Day141 | Incidence and titers of anti-drug antibodies (ADA) to QLS2404 Injection in participants with SLE and pSS; incidence of neutralizing antibodies (NAb), if data permit. |
| Applicable to participants with pSS: The proportion of participants with a ≥ 3-point ESSDAI | from the first subcutaneous Inject of QLS2404 up to Day141. | Description: The minimum ESSDAI score is 0, and the maximum ESSDAI score is 123. A score of 0 indicates no systemic disease activity; a greater score indicates higher systemic disease activity in Sjögren's syndrome. |
Countries
China
Contacts
CONTACTPing Feng, phD
CONTACTQibing Xie, phD
PRINCIPAL_INVESTIGATORPing Feng, phD
West China Hospital
PRINCIPAL_INVESTIGATORQibing Xie, phD
West China Hospital
Outcome results
None listed