Clinical Trial Results:
An open-label phase 2 study to evaluate the safety and efficacy of CCX168 in subjects with IgA Nephropathy on stable RAAS blockade.
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Summary
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EudraCT number |
2014-003402-33 |
Trial protocol |
BE SE |
Global end of trial date |
13 Sep 2015
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Results information
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Results version number |
v2(current) |
This version publication date |
04 Aug 2023
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First version publication date |
21 Oct 2022
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CL005_168
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
IND Number: 123187 | ||
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Sponsors
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Sponsor organisation name |
Chemocentryx Inc
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Sponsor organisation address |
835 Industrial Rd. Suite 600, San Carlos, United States, 94070
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Public contact |
Clinical Operations Manager, ChemoCentryx, Inc. , 1 6502102900,
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Scientific contact |
Clinical Operations Manager, ChemoCentryx, Inc. , 1 6502102900,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
01 Jun 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
13 Sep 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Sep 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
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.
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Protection of trial subjects |
The study was conducted in accordance with the Declaration of Helsinki and with all applicable laws and regulations of the locale and country where the study was conducted, and in compliance with Good Clinical Practice Guidelines. Only subjects that met all the study inclusion and none of the exclusion criteria were entered in the study. The rationale of the study, procedural details, and investigational goals were explained to each subject, along with potential risks and benefits. Each subject was assured of his/her right to withdraw from the study at any time.
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Background therapy |
At screening, subjects ideally were taking one or two RAAS blocker(s) and had BP <140/90 mmHg. If the blood pressure target of <125/75 mmHg was not achieved during the titration period (up to 4 weeks), additional anti-hypertension medication (non-ACE-I or ARBs) was considered to achieve this blood pressure goal (<125/75 mmHg). Once titrated to the optimal RAAS dose, all subjects participated in an 8-week run-in period during which they were required to take a stable MTD of an RAAS blocker before starting treatment with CCX168 on Day 1. If a subject was on two RAAS blockers (any combination of ACE inhibitor, ARB, and aldosterone blocker) at the time of screening, the subject was required to remain on stable doses of those medications throughout the 8-week run-in period. Titration to an MTD for both RAAS blockers was not needed in this case if the blood pressure goal of <125 / 75 mmHg was achieved. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
27 Mar 2015
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
3 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 4
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Country: Number of subjects enrolled |
Sweden: 3
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Worldwide total number of subjects |
7
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EEA total number of subjects |
3
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
7
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||
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Pre-assignment
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Screening 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. | ||||||
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Period 1
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Period 1 title |
Overall study (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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CCX168 | ||||||
Arm description |
Modified Intent-to-Treatment (mITT) Population included all subjects who received at least one dose of study drug and who had at least one post baseline urinary PCR assessment. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
ccx168
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
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.
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Baseline characteristics reporting groups
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Reporting group title |
Overall study
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Reporting group description |
Safety Population included of all subjects who received at least one dose of study drug. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
CCX168
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Reporting group description |
Modified Intent-to-Treatment (mITT) Population included all subjects who received at least one dose of study drug and who had at least one post baseline urinary PCR assessment. | ||
Subject analysis set title |
8-week Run-in period
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
8-week RAAS run-in period
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Subject analysis set title |
12-week treatment period
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
12-week CCX168 treatment period
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Subject analysis set title |
Safety Population
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Safety Population included of all subjects who received at least one dose of study drug.
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End point title |
Change in slope of first morning urinary PCR from the 8-week RAAS blocker run-in period to the 12-week CCX168 treatment period | ||||||||||||||||
End point description |
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
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End point type |
Primary
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End point timeframe |
Week -8 to -1 (Run-in period) and Week 1 to 12 (treatment period)
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Statistical analysis title |
Change in slope uPCR | ||||||||||||||||
Statistical analysis description |
P-value is for the comparison between Slope of Week -8 to -5 and Slope of Week -4 to -1 using random coefficients regression.
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Comparison groups |
8-week Run-in period v 12-week treatment period
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Number of subjects included in analysis |
14
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.965 | ||||||||||||||||
Method |
random coefficients variation | ||||||||||||||||
Parameter type |
Slope | ||||||||||||||||
Point estimate |
-2.4
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Confidence interval |
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95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-133.6 | ||||||||||||||||
upper limit |
128.7 | ||||||||||||||||
Variability estimate |
Standard deviation
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Dispersion value |
141.77
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End point title |
Subject incidence of adverse events (AE's) [1] | ||||||||||||||||||||||||
End point description |
Acronyms use: Adverse Events (AE's) Serious Adverse Events (SAE's)
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End point type |
Primary
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End point timeframe |
Day 0 - Day 169 (throughout the trial)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were performed on this safety endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Proportion of subjects achieving renal response from baseline to day 85 | ||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline and Day 85
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| No statistical analyses for this end point | |||||||||
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End point title |
Proportion of subjects achieving a partial renal response from baseline to day 85 | ||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline and Day 85
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End point title |
Change from Baseline to day 85 in Vital Signs | ||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline to day 85
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Adverse events information
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Timeframe for reporting adverse events |
From Baseline up to 169 days
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
Safety population
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Reporting group description |
Safety population included all subjects who received any CCX168 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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05 Nov 2014 |
The main changes that made Amendment 1.0 to the protocol included the following:
- Exclusion criterion number 12 was added to exclude subjects with infection requiring antibiotic treatment that has not cleared prior to starting CCX168 treatment on Day 1.
- Stopping criteria were added regarding liver enzyme elevations and WBC decreases.
-Modification to the Safety Monitoring Plan.
- Wording added to indicate that the slope of the last 4 weeks of the run-in period may be used as baseline slope instead of the full 8 weeks if steady state has not been reached in the first 4 weeks of the run-in period.
- A statement was added to that if the blood pressure target of <125/75 mmHg is not achieved during the titration period, additional anti-hypertension medication (non-ACE-I or ARBs) should be considered to achieve this blood pressure goal.
- Several sections were revised to reflect addition of PK assessment in patients with IgA nephropathy.
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13 May 2015 |
The main changes that Amendment 2.0 made to the protocol included the following:
- Inclusion of serum amylase and lipase monitoring over the course of the study.
- Monitoring of central nervous system function
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17 Jul 2015 |
The main change that Amendment 3.0 made to the protocol included the following:
-Modified stopping rules for individual subjects, based on white blood cell, neutrophil, and lymphocyte counts, as well as hepatic aminotransferase or bilirubin elevations
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
