Open-Label Study to Evaluate Safety and Efficacy of CCX168 in Subjects With IGA Nephropathy on Stable RAAS Blockade

An Open-Label Phase 2 Study to Evaluate the Safety and Efficacy of CCX168 in Subjects With Immunoglobulin A Nephropathy on Stable RAAS Blockade

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02384317

Enrollment

Registered

2015-03-10

Start date

2015-03-27

Completion date

2018-06-01

Last updated

2025-03-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Immunoglobulin A Nephropathy

Brief summary

The primary safety objective of this study is to evaluate the safety and tolerability of CCX168 in subjects with IgAN on background supportive therapy with a maximally tolerated dose of RAAS blockade. The primary efficacy objective is to evaluate the efficacy of CCX168 based on an improvement in proteinuria.

Detailed description

Study acquired by Amgen and all disclosures were done by previous sponsor ChemoCentryx.

Interventions

DRUGCCX168

CCX168 30 mg, twice daily (b.i.d.) orally for 84 days (12 weeks). The CCX168 dose was taken in the morning, optimally within one hour after breakfast, and in the evening, optimally within one hour after dinner.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Key Inclusion Criteria: * Diagnosis of Immunoglobulin A nephropathy * estimated glomerular filtration rate \>60 mL/min/1.73 m2 * Proteinuria (first morning urinary protein:creatinine ratio \>1g/g creatinine) Key

Exclusion criteria

* Severe renal disease * Pregnant or nursing * Proteinuria \>8g/g creatinine or \>8g/day * Systemic manifestations of Henoch-Schonlein purpura within 2 years prior * Patients with Immunoglobulin A nephropathy deemed secondary to underlying disease * Biopsy reported severe crescentic Immunoglobulin A nephropathy * History of treatment with glucocorticoids, cyclophosphamide, azathioprine, mycophenolate mofetil, or any biologic immunomodulatory agent with 24 weeks prior * History of clinically significant cardiac conditions * History of cancer within 5 years prior * Any infection requiring antibiotic treatment that has not cleared prior to study start

Design outcomes

Primary

Measure	Time frame	Description
Change in Slope of First Morning Urinary PCR From the 8-week RAAS Blocker run-in Period to the 12-week CCX168 Treatment Period	Week -8 to -1 (Run-in period) and Week 1 to 12 (treatment period)	The mean change in the slope of the urinary protein:creatinine ratio (UPCR, in mg/g/week) between the 8-week run-in period and the 12-week treatment period
Number of Participants With AE's	Day 0 - Day 169 (throughout the trial)	Acronyms use: Adverse Events (AE's) Serious Adverse Events (SAE's)
Severity of Adverse Events (AE's)	Day 0 - Day 169 (throughout the trial)	Acronyms use: Adverse Events (AE's) Serious Adverse Events (SAE's)

Secondary

Measure	Time frame	Description
Change in Systolic Blood Pressure From Baseline to Day 85	Baseline to day 85	—
Change in Diastolic Blood Pressure From Baseline to Day 85	Baseline to day 85	—
Proportion of Subjects Achieving Renal Response From Baseline to Day 85	Baseline and Day 85	Renal Response defined as an improvement in proteinuria based on a decrease from baseline to Day 85 in proteinuria to a level \<300 mg/g creatinine and maintaining eGFR within 15% of baseline.
Change in Weight From Baseline to Day 85	Baseline to day 85	—
Change in Temperature From Baseline to Day 85	Baseline to day 85	—
Proportion of Subjects Achieving a Partial Renal Response From Baseline to Day 85	Baseline and Day 85	A partial renal response, defined as an improvement in proteinuria based on a decrease from baseline to Day 85 in proteinuria to a level \<1 g/g creatinine and maintaining eGFR within 15% of baseline.
Change From Baseline to Day 85 in Vital Signs	Baseline to day 85	—

Countries

Sweden, United States

Participant flow

Pre-assignment details

Screening took place for 14 days. Screening was following by a combined renin-angiotensin-aldosterone system (RAAS) titration (up to 4 weeks) plus run-in period (8 weeks) with an additional up to 7-day eligibility confirmation.

Participants by arm

Arm	Count
Overall Study Safety Population included of all subjects who received at least one dose of study drug.	7
Total	7

Baseline characteristics

Characteristic	Overall Study
ACR	1528.42 mg/g
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	7 Participants
Age, Continuous	44.1 years STANDARD_DEVIATION 13.2
BMI	30.05 kg/m² STANDARD_DEVIATION 8.29
eGFR	65.89 mL/min/1.73m²
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
MCP-1 to Creatinine ratio	577.44 pg/mg crea
Mean time since diagnosis of IgAN	17.3 month
PCR	1906.84 mg/g
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	1 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	6 Participants
Region of Enrollment Sweden	3 Participants
Region of Enrollment United States	4 Participants
Sex: Female, Male Female	4 Participants
Sex: Female, Male Male	3 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 7
other Total, other adverse events	7 / 7
serious Total, serious adverse events	1 / 7

Outcome results

Primary

Change in Slope of First Morning Urinary PCR From the 8-week RAAS Blocker run-in Period to the 12-week CCX168 Treatment Period

The mean change in the slope of the urinary protein:creatinine ratio (UPCR, in mg/g/week) between the 8-week run-in period and the 12-week treatment period

Time frame: Week -8 to -1 (Run-in period) and Week 1 to 12 (treatment period)

Arm	Measure	Value (MEAN)
CCX168	Change in Slope of First Morning Urinary PCR From the 8-week RAAS Blocker run-in Period to the 12-week CCX168 Treatment Period	-2.4 mg/g/week
8-week Run-in Period	Change in Slope of First Morning Urinary PCR From the 8-week RAAS Blocker run-in Period to the 12-week CCX168 Treatment Period	15.3 mg/g/week
12-week Treatment Period	Change in Slope of First Morning Urinary PCR From the 8-week RAAS Blocker run-in Period to the 12-week CCX168 Treatment Period	-23.9 mg/g/week

p-value: 0.96595% CI: [-133.6, 128.7]Random coefficients regression

Primary

Number of Participants With AE's

Acronyms use: Adverse Events (AE's) Serious Adverse Events (SAE's)

Time frame: Day 0 - Day 169 (throughout the trial)

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
CCX168	Number of Participants With AE's	Subjects who had any AE	7 Participants
CCX168	Number of Participants With AE's	Subjects who had an SAE	1 Participants
CCX168	Number of Participants With AE's	Subjects who had an AE possibly related	5 Participants

Primary

Severity of Adverse Events (AE's)

Acronyms use: Adverse Events (AE's) Serious Adverse Events (SAE's)

Time frame: Day 0 - Day 169 (throughout the trial)

Arm	Measure	Group	Value (NUMBER)
CCX168	Severity of Adverse Events (AE's)	AE leading to interruption of treatment	1 Number of AEs
CCX168	Severity of Adverse Events (AE's)	AE leading to permanent discontinuation of study	0 Number of AEs
CCX168	Severity of Adverse Events (AE's)	Withdrawals due to AE	0 Number of AEs
CCX168	Severity of Adverse Events (AE's)	Deaths	0 Number of AEs
CCX168	Severity of Adverse Events (AE's)	AE of grade 3 ≥	1 Number of AEs
CCX168	Severity of Adverse Events (AE's)	Related AE grade 3≥	0 Number of AEs

Secondary