Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of KP104 to Treat Glomerulonephritis

NCT05517980 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: KP104-203
• Study Type: interventional
• Target: 52
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of KP104 in participants with IgAN and C3G. The study will start with enrolling the IgAN cohort. Approximately 42 participants with IgAN will be enrolled in 2 stages: Stage 1 will be used to collect safety, immunogenicity, PK, and PD data to select the optimal biologic dose (OBD) of KP104 for IgAN, as well as to preliminarily explore the effect of KP104 on C3G. Stage 2 will be used to collect safety, immunogenicity, PK, PD, and efficacy data at the OBD dose of KP104 for IgAN and C3G. As soon as the OBD for IgAN is determined, eligible participants with C3G will be enrolled and dosed at the OBD for IgAN for a minimum of 48 weeks for weekly maintenance dosing and a minimum of 47 weeks for biweekly maintenance dosing. Approximately 10 participants with C3G will be enrolled.

Conditions

Glomerulonephritis

Keywords

KP104; Immunoglobulin A Nephropathy; Compliment-mediated Glomerulonephritis; Complement Inhibitor

Outcome Measures

Primary Outcomes (1)

• Percent change from Baseline in 24-hour urinary protein creatinine ratio (UPCR) at Week 24 (C3G) for participants in Stage 2

  The UPCR will be calculated as percent change in protein (Pr)/ Creatinine (Cr).

  Baseline and at Week 24

Secondary Outcomes (6)

• Number of participants reporting Treatment-Emergent Adverse Events (TEAEs)

  Up to 56 Weeks

• Number of participants reporting Treatment-Emergent Serious Adverse Events (TESAEs)

  Up to 56 Weeks

• Number of participants reporting AEs of Special Interest (AESIs)

  Up to 56 Weeks

• Maximum concentration (Cmax) of KP104

  At Baseline (Day 1), Days 8, 15, 22, 29, 43, 57, 85, 169, 253, 337, 365 and 395

• Trough concentration (Ctrough) of KP104 at steady state

  At Baseline (Day 1), Days 8, 15, 22, 29, 43, 57, 85, 169, 253, 337, 365 and 395

Study Arms (6)

IgAN Cohort Stage 1 Dose 1

EXPERIMENTAL

Participants will be randomized to receive weekly or biweekly maintenance doses of KP104 at Dose 1. Participants in Stage 1 will also have the opportunity to be switched to the OBD if they are still in the treatment period.

Drug: KP104

C3G Cohort Stage 1 Dose 1

EXPERIMENTAL

Participants will be randomized to receive weekly or biweekly maintenance doses of KP104 at Dose 1. Participants in Stage 1 will also have the opportunity to be switched to the OBD if they are still in the treatment period.

Drug: KP104

IgAN Cohort Stage 1 Dose 2

EXPERIMENTAL

Participants will be randomized to receive weekly or biweekly maintenance doses of KP104 at Dose 2. Participants in Stage 1 will also have the opportunity to be switched to the OBD if they are still in the treatment period.

Drug: KP104

C3G Cohort Stage 1 Dose 2

EXPERIMENTAL

Participants will be randomized to receive weekly or biweekly maintenance doses of KP104 at Dose 2. Participants in Stage 1 will also have the opportunity to be switched to the OBD if they are still in the treatment period.

Drug: KP104

IgAN Cohort Stage 2

EXPERIMENTAL

Participants will receive weekly or biweekly maintenance doses of KP104 at the OBD.

Drug: KP104

C3G Cohort Stage 2

EXPERIMENTAL

Participants will receive weekly or biweekly maintenance doses of KP104 at the OBD.

Drug: KP104

Interventions

KP104 DRUG

Participants will receive loading and/or weekly maintenance subcutaneous (SC) doses of KP104.

C3G Cohort Stage 1 Dose 1; C3G Cohort Stage 1 Dose 2; C3G Cohort Stage 2; IgAN Cohort Stage 1 Dose 1; IgAN Cohort Stage 1 Dose 2; IgAN Cohort Stage 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Weight of \>35 kilograms (kg) at Screening
• Body mass index (BMI) of \<35 kilograms per square meter (kg/m\^2)
• UPCR \>1.0 grams per gram (g/g) by 24-hour urine collection at Screening
• Documented diagnosis and clinical status of IgAN or C3G as follows:
• IgAN:
• Diagnosis of IgAN verified by biopsy taken within the past 3 years prior to enrolment.
• On stable regimen of angiotensin converting enzyme or angiotensin blocking agents for 12 weeks and/or sodium-glucose cotransporter-2 (SGLT2) inhibitors for 6 weeks at Screening
• C3G:
• Diagnosis of C3G verified by biopsy taken within the past 3 years prior to enrolment.
• On stable regimen of angiotensin converting enzyme or angiotensin blocking agents for 12 weeks and/or SGLT2 inhibitors for 6 weeks at Screening
• Females of childbearing potential and males must practice effective contraception from Screening until 28 days after the end of study (EOS) visit.
• Females of childbearing potential must have a negative pregnancy test at Screening and within 1 day prior to dosing of study drug

You may not qualify if:

• Any clinically significant, poorly controlled underlying illness other than IgAN or C3G, as determined by the investigator
• Treatment of any infection with IV (within 30 days of Screening) or oral (within 14 days of Screening) antibiotics, antivirals, or antifungals
• History of infections with encapsulated organisms
• History of untreated tuberculosis
• Positive serology for hepatitis C virus (HCV) ribonucleic acid (RNA) or human immunodeficiency virus (HIV) at Screening
• History of bone marrow or stem cell transplantation
• Absolute neutrophil count (ANC) \<500 cells per microliter (cells/μL)
• eGFR \<30 milliliters per minute per 1.73 square meter (mL/min/1.73 m\^2) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
• Presence of crescent formation in \>50 percent (%) of glomeruli assessed on renal biopsy
• Nephrotic syndrome defined as presence of substantial proteinuria (\> 3.5 g/24 hours), hypoalbuminemia (\< 30 grams per liter \[g/L\]), and edema/hyperlipidemia. Nephrotic range proteinuria alone is acceptable.
• Rapidly progressive glomerulonephritis, defined as a fall in eGFR of \> 30 mL/min/1.73 m\^2 within 24 weeks prior to the Screening Visit
• Receiving renal replacement therapy or anticipated to require renal replacement therapy during the duration of the study

Sponsors & Collaborators

• Kira Pharmacenticals (US), LLC.: lead

MeSH Terms

Conditions

Glomerulonephritis; Glomerulonephritis, IGA

Condition Hierarchy (Ancestors)

Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Study Director

CONTACT

privacy@kirapharma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2022
• First Posted: August 26, 2022
• Study Start: March 1, 2025
• Primary Completion: March 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: October 28, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share