Study to Evaluate Safety, Tolerability and Pharmacodynamics of KP104 in Participants With Thrombotic Microangiopathy Secondary to Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of KP104 in participants with systemic lupus erythematosus (SLE)-Thrombotic microangiopathy (TMA). The study consists of 2 parts: Part 1 (Dose Optimization) and Part 2 (Proof of Concept). All participants will receive KP104 in combination with standard of care (SOC) for SLE-TMA.

Official Title
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An Open-label, Phase 2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of KP104 in Subjects With Thrombotic Microangiopathy Secondary to Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: KP104


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets criteria for SLE per the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria. Decrease in platelet count to less than (<)150,000/microliters (mcL). Abnormal renal function. Females of childbearing potential with negative pregnancy test and males must agree to practice effective contraception from Screening until 28 days after the End of study (EOS) visit. Willing and able to provide informed consent. Evidence of microangiopathic hemolytic anemia Exclusion Criteria: Diagnosis of other TMA syndromes. A renal biopsy within 7 days of screening that shows exclusively chronic changes of TMA. Positive Coombs test at the time of TMA diagnosis. Active or unresolved Neisseria meningitidis infection at screening. Only key inclusion and exclusion criteria have been included.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Dose Optimization Cohort 1, Dose 1<br>Participants will be administered with KP104 as a weekly maintenance dose for 24 Weeks. After the last participant completes 6 weeks of treatment, all available data, including safety, PK, PD, and modeling results, will be reviewed by the Internal Data Review Committee (IDRC) to determine Dosing Regimen 2 | Drug: KP104<br>* KP104 will be administered.<br>|
| Experimental: Part 1: Dose Optimization Cohort 2, Dose 2<br>Participants will be administered with KP104 dose regimen 2 for 24 Weeks. After the last participant completes 6 weeks of treatment, all available data, including safety, PK, PD, and modeling results, will be reviewed by the IDRC to determine Dosing Regimen 3. | Drug: KP104<br>* KP104 will be administered.<br>|
| Experimental: Part 1: Dose Optimization Cohort 3, Dose 3<br>Participants will be administered with KP104 dose regimen 3 for 24 Weeks. After the last participant completes 6 weeks of treatment, all available data, including safety, PK, PD, and modeling results, will be reviewed by IDRC to determine the Optimal biologic dose (OBD) for Part 2. | Drug: KP104<br>* KP104 will be administered.<br>|
| Experimental: Part 2: OBD Cohort, Dose 4<br>Participants will be administered with KP104 OBD for 24 Weeks. | Drug: KP104<br>* KP104 will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts 1 and 2: Number of participants with Treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs) and Adverse events of special interest (AESIs) |  | Up to 24 weeks | 
| Part 2: Percent change from Baseline in platelet count |  | Baseline (Day 1) and up to Week 12 | 
| Part 2: Percent change from Baseline in serum lactate dehydrogenase (LDH) levels |  | Baseline (Day 1) and up to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dose Selection, Systemic lupus erythematosus, Thrombotic microangiopathy, Proof of Concept, KP-104