Clinical Trials Register

Summary
EudraCT Number:	2014-003402-33
Sponsor's Protocol Code Number:	CL005_168
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-12-29
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Sweden - MPA

A.2

EudraCT number

2014-003402-33

A.3

Full title of the trial

An open-label phase 2 study to evaluate the safety and efficacy of CCX168 in subjects with IgA Nephropathy on stable RAAS blockade.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

An open-label phase 2 study to evaluate the safety and efficacy of CCX168 in subjects with IgA Nephropathy on stable RAAS blockade.

A.4.1

Sponsor's protocol code number

CL005_168

A.5.4

Other Identifiers

Name:

IND Number

Number:

123187

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ChemoCentryx, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	ChemoCentryx, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ChemoCentryx, Inc.
B.5.2	Functional name of contact point	Clinical Operations Manager
B.5.3	Address:
B.5.3.1	Street Address	850 Maude Ave
B.5.3.2	Town/ city	Mountain View, California
B.5.3.3	Post code	94043
B.5.3.4	Country	United States
B.5.4	Telephone number	+31(0)630892290
B.5.5	Fax number	+1650-210-2910
B.5.6	E-mail	apotarca@chemocentryx.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	CCX168
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	CCX168
D.3.9.3	Other descriptive name	CCX168
D.3.9.4	EV Substance Code	SUB31899
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10mg per capsule
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

IgAN is reported as the most common glomerulonephritis worldwide. It is associated with a wide spectrum of disease severity and rate of progression of renal failure.

IgA nefropathie wordt wereldwijd gezien als de meest voorkomende glomeruloneprhitis. Het wordt geassocieerd met een breed spectrum aan ernstige ziektebeelden en versnelling van progressieve nierfalen.

E.1.1.1

Medical condition in easily understood language

IgAN is reported as the most common glomerulonephritis worldwide. It is associated with a wide spectrum of disease severity and rate of progression of renal failure.

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	PT
E.1.2	Classification code	10021263
E.1.2	Term	IgA nephropathy
E.1.2	System Organ Class	10038359 - Renal and urinary disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

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.

De belangrijkste veiligheidsdoelstelling van dit onderzoek is het evalueren van de veiligheid en verdraagbaarheid van CCX168 bij proefpersonen met IgAN en ondersteunende behandeling met de maximale verdraagbare dosis RAAS-blokkade.
Tevens wordt de werkzaamheid van de behandeling met CCX168 beoordeeld op basis van de hoeveelheid eiwitten in de urine en de nierfunctie.

E.2.2

Secondary objectives of the trial

1. Change in albuminuria with CCX168 treatment
2. Change in renal function based on eGFR with CCX168 treatment
3. Change in hematuria with CCX168 treatment
4. Change in renal inflammatory activity based on urinary monocyte chemoattractant protein-1 (MCP 1):creatinine ratio and urinary epidermal growth factor (EGF):MCP-1 ratio with CCX168 treatment
5. Change in serum IgA: plasma C3 ratio with CCX168 treatment
6. Changes in pharmacodynamic markers in plasma and urine with CCX168 treatment, e.g., C3a, C5a, properdin, and sC5b-9

1 Verandering in albuminurie met CCX168 behandeling
2 Verandering van de nierfunctie gebaseerd op de eGFR met CCX168 behandeling
3 Verandering van de hematurie met CCX168 behandeling
4 Verandering in de renale inflammatoire activiteit op basis van urine monocyten chemoattractant eiwit-1 (MCP 1): creatinine ratio en urine epidermale groeifactor (EGF): MCP-1-ratio met CCX168 behandeling
5 Verandering in de serum IgA: plasma C3 verhouding met CCX168 behandeling
6 Veranderingen in farmacodynamische markers in plasma en urine met CCX168 behandeling, bijvoorbeeld C3a, C5a, properdin en sC5b-9.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Biopsy-proven IgAN performed for clinical purposes within 3 years prior to screening
2. eGRF>60 mL/min/1.73 m² (by MDRD equation) OR eGFR >45 mL/min/1.73 m² if eGFR has not declined < 10 mL/min/1.73 m² over the previous 24 weeks
3. Proteinuria, defined as first morning urinary PCR > 1g/g creatinine
4. Male or female subjects, aged at least 18 years; where allowed by local regulations, female subjects of childbearing potential may participate if adequate contraception is used during, and for at least the three months after study completion; male subjects with partners of childbearing potential may participate in the study if they had a vasectomy at least 6 months prior to randomization or if adequate contraception is used during, and for at least the three months after study completion; Adequate contraception is defined as resulting in a failure rate of less than 1% per year (combined estrogen and progestogen (oral, intravaginal, or transdermal), or progestogen-only hormonal contraception (oral, injectable, or implantable), intra-uterine device, intra-uterine hormone releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence)
5. Willing and able to give written Informed Consent and to comply with the requirements of the study protocol
6. Judged to be otherwise healthy by the Investigator, based on medical history, physical examination, and clinical laboratory assessments. Subjects with clinical laboratory values that are outside of normal limits (other than those specified in the Exclusion Criteria) and/or with other abnormal clinical findings that are judged by the Investigator not to be of clinical significance, may be entered into the study

E.4

Principal exclusion criteria

1. Severe renal disease as determined by rapid decline in eGFR (defined as > 10 mL/min/1.73m² over 24 weeks prior to screening, not otherwise explained)
2. Pregnant or nursing
3. Proteinuria > 8 g/day (or>8g/g creatinine)
4. Patients with systemic manifestations of Henoch-Schönlein purpura within the last 2 years prior to screening.
5. Patients with IgAN deemed secondary to underlying disease: e.g., diabetes, liver disease, cirrhosis, celiac disease, HIV, inflammatory bowel disease, lymphoma, or associated with any other multi-system autoimmune disease
6. Biopsy report demonstrating severe crescentic IgAN (>25% crescents), OR>50% interstitial fibrosis and/or tubular atrophy ("T2") (Cattran et al. 2009), OR a high likelihood of rapid decline in eGFR based on an MEST ("Oxford") classification (M=mesangial hypercellularity; E=endocapillary proliferation; S=segmental glomerulosclerosis/adhesion; T=tubular atrophy/interstitial fibrosis) score of M1, E0, T1, or M0/1, E1, T1 (Cattran et al. 2009)
7. History of treatment with glucocorticoids, cyclophosphamide, azathioprine, mycophenolate mofetil, or any biologic immunomodulatory agent within the 24 weeks prior to screening
8. Symptomatic congestive heart failure requiring prescription medication, clinically evident peripheral edema of cardiac origin, poorly-controlled hypertension (systolic blood pressure>160 or diastolic blood pressure >95), history of unstable angina, myocardial infarction or stroke within 6 months prior to screening
9. History or presence of any form of cancer within the 5 years prior to screening, with the exception of excised basal cell or squamous cell carcinoma of the skin, or cervical carcinoma in situ or breast cacrinoma in situ that has been excised or resected completely and is without evidene of local recurrence or metastasis
10. Positive HBV, HCV, or HIV viral screening test
11. History of tuberculosis
12. Any infection requiring antibiotic treatment that has not cleared prior to starting CCX168 treatment on Day 1;
13. WBC count less than 4000/uL, or neutrophil count less than 2000/uL, or lymphocyte count less than 1000/uL
14. Hemoglobin less than 9 g/dL (or 5.56 mmol/L) at screening
15. Evidence of hepatic disease; AST, ALT, alkaline phosphatase, or bilirubin > 3 x the upper limit of normal
16. Participated in any clinical study of an investigational product within 30 days prior to screening or within 5 half-lives after taking the last dose
17. History of presence of any medical condition or disease which, in the opinion of the Investigator, may place the subject at unacceptable risk for study participation

E.5 End points

E.5.1

Primary end point(s)

The primary safety endpoint is the subject incidence of adverse events. The primary efficacy endpoint is the change in slope of first morning urinary PCR from the 8-week RAAS blocker run-in period to the 12-week CCX168 treatment period

E.5.1.1

Timepoint(s) of evaluation of this end point

Day85

E.5.2

Secondary end point(s)

Safety: 1. Change from baseline in all safety laboratory parameters
2. Change from baseline in vital signs
Efficacy: 1. The proportion of subjects achieving renal response, defined as an improvement in proteinuria based on a decrease from baseline to Day 85 in proteinuria to a level < 300mg/g creatinine and maintaining estimated glomerular filtration rate (eGFR) within 15% of baseline
2. The proportion of subjects achieving a partial renal response, defined as an improvement in proteinuria based on a decrease from baseline to Day 85 in proteinuria to a level <1g/g creatinine and maintinaing estimated glomerular filtration rate (eGFR) within 15% of baseline
3. Change in slope from the run-in period to the treatment period for urinary ACR, eGFR, urinary MCP-1: creatinine, urinary EGF:MCP-1, and urinary microscopic RBC counts
4. The percent change from baseline to Day 85 in urinary PCR and ACR
5. The change from baseline to Day 85 in eGFR
6. In patients with hematuria at baseline, the percent change from baseline in urinary RBC count
7. The percent change from baseline to Day 85 in urinary MCP-1: creatinine ratio
8. The percent change from baseline to Day 85 in serum IgA:plasma C3 ratio
9. The percent change from baseline to Day 85 in urinary EGF:MCP-1 ratio
10. The percent change from baseline in plasma and urinary biomarker, e.g., C3a, C5a, properdin, and sC5b-9

E.5.2.1

Timepoint(s) of evaluation of this end point

Changes from baseline in all efficacy measurements at time points other than day 85 will also be assessed.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Belgium

Sweden

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

SOC

Geen

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-02-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-02-04

P. End of Trial
P.	End of Trial Status	Completed

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