Clinical Trials Register

Summary
EudraCT Number:	2011-001267-49
Sponsor's Protocol Code Number:	CL005_140
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-08-16
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

Czechia - SUKL

A.2

EudraCT number

2011-001267-49

A.3

Full title of the trial

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of CCX140-B in Diabetic Nephropathy

A.3.1

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

A Clinical Trial to Evaluate the Safety and Efficacy of CCX140-B, an investigational drug for the treatment of Diabetic Nephropathy

A.4.1

Sponsor's protocol code number

CL005_140

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	Medpace
B.5.2	Functional name of contact point	Medpace Regulatory Submissions
B.5.3	Address:
B.5.3.1	Street Address	Gmunder Strasse 53
B.5.3.2	Town/ city	Munich
B.5.3.3	Post code	81379
B.5.3.4	Country	Germany
B.5.4	Telephone number	4989895 57 180
B.5.5	Fax number	4989895 571 81 00
B.5.6	E-mail	regsubmissions@medpace.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	CCX140-B
D.3.2	Product code	CCX140-B
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	CCX140-B
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	2.5
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Diabetic Nephropathy

E.1.1.1

Medical condition in easily understood language

Kidney disease or damage that results as a complication of diabetes.

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10061835
E.1.2	Term	Diabetic nephropathy
E.1.2	System Organ Class	10038359 - Renal and urinary disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary safety objective is to evaluate the safety and tolerability of
CCX140-B, based on subject incidence of adverse events over 52 weeks
of treatment, in subjects with diabetic nephropathy (DN).
Primary efficacy objective is to evaluate the efficacy of CCX140-B,
compared to placebo, over 52 weeks of placebo-controlled treatment
based on changes from baseline in first morning urinary albumin:
creatinene ratio (ACR)

E.2.2

Secondary objectives of the trial

Evaluation of the efficacy of CCX140-B, compared to placebo, based on changes from baseline in:
1. Estimated glomerular filtration rate (eGFR) and
2. Hemoglobin A1c (HbA1c)
Other study objectives include:
1.Evaluation of the effect of CCX140-B on other renal parameters including estimated
glomerular filtration rate (eGFR), serum creatinine, blood urea nitrogen (BUN), and
serum phosphorus;
2.Evaluation of the effect of CCX140-B on fasting plasma glucose (FPG), fasting plasma
insulin and homeostasis model assessment of insulin resistance (HOMA-IR);
3.Evaluation of the effect of CCX140-B treatment on urinary monocyte chemoattractant
protein-1 (MCP-1):creatinine ratio and plasma MCP-1 concentrations;
4.Evaluation of the safety of CCX140-B based on changes in safety laboratory
parameters, vital signs, and physical examination findings; and
5.Assessment of plasma concentration profile of CCX140 and possible metabolites in
subjects with DN.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Male or female, aged 18-75 years inclusive, with documented previously diagnosed type 2 diabetes mellitus (per American Diabetes Association [ADA] criteria);
2.Residual albuminuria despite stable ACE inhibitor or ARB therapy for at least 8 weeks prior to screening (ACR of 100 to 3000 mg albumin/g creatinine, inclusive, based on two values obtained from two first morning urine samples taken on two separate days during the screening period; both ACR values must be 100 to 3000 mg albumin/g creatinine, inclusive);
3.Estimated glomerular filtration rate based on serum creatinine (eGFR, determined by Modification of Diet in Renal Disease [MDRD] equation) of ≥ 25 mL/min/1.73 m2 based on two values obtained from two blood samples taken on two separate days during the screening period; both eGFR values must be ≥ 25 mL/min/1.73 m2;
4.Must have been on a stable dose of either an angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) for at least 8 weeks prior to screening. The dose of these drugs must not be lower than the lowest labeled dose. Subjects may not be on both an ACE inhibitor and an ARB. Doses of any other anti-hypertension treatment must have been stable for at least 4 weeks prior to screening;
5.Any anti-diabetic treatment must have been maintained at stable dose(s) for at least 8 weeks prior to screening;
6.If on any lipid lowering drug, the subject must have been on a stable dose for at least 4 weeks prior to screening;
7.If taking any phosphate binders, cinacalcet, vitamin D or vitamin D analogues, must have been on stable doses for at least 4 weeks prior to screening;
8.Hemoglobin A1c (HbA1c) > 6.0% but not > 10.0% and fasting plasma glucose less than 270 mg/dL at screening;
9.Willing and able to give written Informed Consent and to comply with the requirements of the study protocol;
10.Judged to be otherwise healthy by the Investigator, based on medical history, physical examination (including electrocardiogram [ECG]), 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; and
11.Female subjects of childbearing potential, and male subjects with partners of childbearing potential, may participate if adequate contraception is used during, and for at least the four weeks after, any administration of study medication. Adequate contraception is defined as usage by at least one of the partners of a barrier method of contraception, together with usage by the female partner, commencing at least three months prior to Screening, of a stable regimen of any form of hormonal contraception or an intra-uterine device. Use of abstinence alone is not considered adequate. Use of a barrier method alone is considered adequate only if the male partner was vasectomized at least six months prior to Screening. Use of a double-barrier method of contraception is acceptable. Women of childbearing potential must have a negative serum pregnancy test during the screening period and a negative urine pregnancy test on the day of initial dosing.

E.4

Principal exclusion criteria

1.Type 1 diabetes mellitus or history of diabetic ketoacidosis;
2.Previous renal transplant or known non-diabetic renal disease, except related to hypertension;
3.Has undergone renal dialysis at any time in the past;
4.Women who are pregnant or breastfeeding;
5.Body mass index (BMI) above 45.4 kg/m2;
6.Received chronic (more than 7 days continuously) systemic glucocorticoid or other immunosuppressive treatment within 8 weeks of screening;
7.Use of bardoxolone, atrasentan or other endothelin antagonist within 8 weeks prior to screening;
8.Received chronic (more than 7 days continuously) NSAID treatment within 2 weeks prior to screening;
9.Cardiac failure (class III or IV), history of unstable angina, symptomatic coronary artery disease, myocardial infarction or stroke within 12 weeks prior to screening;
10.Poorly-controlled blood pressure (systolic blood pressure >155 or diastolic blood pressure >95, with blood pressure measured in the seated position after at least 5 minutes of rest);
11.History of hypersensitivity to ingredients of the placebo (tartrazine, microcrystalline cellulose, starch, or croscarmellose sodium);
12.History or presence of leukopenia (WBC count <3.5 x 109/L);
13.History or presence of any form of cancer within the 5 years prior to randomization, with the exception of excised basal cell or squamous cell carcinoma of the skin, or cervical carcinoma in situ or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis;
14.Presence of tuberculosis based on chest X rays, tuberculin skin test, QuantiFERON®-TB Gold test, or T-SPOT®.TB test performed during screening; If screening test is performed and it is deemed positive due to previous vaccination or TB exposure, chest X rays must be acquired to rule out TB;
15.Positive HBV, HCV, or HIV viral screening test;
16.History of gastrointestinal conditions that may interfere with study medication compliance, e.g., severe gastroparesis, with regurgitation of food or oral medication;
17.History of alcohol or illicit drug abuse;
18.Any infection requiring antibiotic treatment within 4 weeks prior to screening;
19.Hemoglobin less than 10 g/dL (or 6.18 mmol/L) at screening;
20.Evidence of hepatic disease; AST, ALT, or bilirubin > 2 x the upper limit of normal;
21.Clinically significant abnormal ECG during screening, e.g., QTc greater than 450 msec;
22.Participated in any clinical study of an investigational product within 30 days prior to randomization; and
23.History or 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)

Efficacy end point:
Percent change of morning urinary ACR

Safety end point:
Nature, frequency and severity of adverse events

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline to Day 365 (week 52)

E.5.2

Secondary end point(s)

The secondary efficacy end points:
Changes in eGFR

Other end points
1. Serum creatinine, BUN and serum phosphorus
2. Fasting plasma glucose, insulin, and HOMA-IR; and
3. Urinary MCP-1: creatinine ratio and plasma MCP-1

PK analysis

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline to Day 365 (week 52)

PK - Day 1 through Day 393

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

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

100

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

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 years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

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:

180

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

270

F.4.2.2

In the whole clinical trial

270

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)

Normal treatment of that condition

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

2011-11-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-11-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-08-04

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