Clinical Trials Register

Summary
EudraCT Number:	2011-003049-16
Sponsor's Protocol Code Number:	CL007_140
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-08-01
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

Netherlands - Competent Authority

A.2

EudraCT number

2011-003049-16

A.3

Full title of the trial

A Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Effect of CCX140-B on Albuminuria in Subjects with Type 2 Diabetes Mellitus

A.3.1

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

The effect of a novel drug (CCX140-B) on albuminuria in patients with type 2 diabetes mellitus

A.3.2

Name or abbreviated title of the trial where available

CCX140-B T2DM albuminuria

A.4.1

Sponsor's protocol code number

CL007_140

A.5.4

Other Identifiers

Name:

Centre for Human Drug Research

Number:

CHDR1112

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	Senior Clinical Operations Manager
B.5.3	Address:
B.5.3.1	Street Address	850 Maude Avenue
B.5.3.2	Town/ city	Mountain View
B.5.3.3	Post code	CA 94043
B.5.3.4	Country	United States
B.5.4	Telephone number	16502102923
B.5.5	Fax number	16502102910
B.5.6	E-mail	djohnson@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	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.3.9.1	CAS number	1100319-36-5
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

Type 2 Diabetes Mellitus, nephropathy, albuminuria

E.1.1.1

Medical condition in easily understood language

Type 2 Diabetes Mellitus, renal disease, protein excretion (urine)

Suikerziekte, nierziekte, eiwituitscheiding (urine)

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	HLT
E.1.2	Classification code	10012602
E.1.2	Term	Diabetes mellitus (incl subtypes)
E.1.2	System Organ Class	10014698 - Endocrine disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	PT
E.1.2	Classification code	10027525
E.1.2	Term	Microalbuminuria
E.1.2	System Organ Class	10038359 - Renal and urinary disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
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.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	PT
E.1.2	Classification code	10001580
E.1.2	Term	Albuminuria
E.1.2	System Organ Class	10038359 - Renal and urinary disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10045242
E.1.2	Term	Type II diabetes mellitus
E.1.2	System Organ Class	10027433 - Metabolism and nutrition 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

To evaluate the effect of CCX140-B treatment on urinary albumin excretion in subjects with type 2 diabetes mellitus with albuminuria, and to evaluate the safety and tolerability of CCX140-B in subjects with type 2 diabetes mellitus with albuminuria

E.2.2

Secondary objectives of the trial

1.To evaluate the effect of CCX140-B on hemoglobin A1c (HbA1c);
2.To evaluate the pharmacokinetic (PK) profile of CCX140-B in subjects with T2DM with albuminuria;
3.To evaluate the effect of CCX140-B on renal function; and
4.To evaluate the effect of CCX140-B on urinary MCP-1:creatinine ratio, and other serum and urinary markers of renal function and inflammation.

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), and treated with oral antidiabetic drugs;
2.Albumin:creatinine ratio (ACR) of 200 to 3000 mg/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 200 to 3000 mg/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;
4.All subjects must be on a stable dose an ACE inhibitor or 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.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;
6.Fasting plasma glucose less than 270 mg/dL at screening;
7.Willing and able to give written Informed Consent and to comply with the requirements of the study protocol;
8.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
9.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 prior to the 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 of screening;
8.Received chronic (more than 7 days continuously) NSAID treatment within 2 weeks of screening;
9.Cardiac failure (class III or IV), history of unstable angina, symptomatic coronary artery disease, myocardial infarction or stroke within 12 weeks of 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 of 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.Participation in another clinical trial within 3 months prior to the start of this study or more than 4 times per year; 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)

Urinary albumin excretion
Safety and tolerability

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 1 (only safety), 2, 3, 8, 14, 15, 29, 57, 84, 85, 113; day 1 being the first day of administration

E.5.2

Secondary end point(s)

HbA1c
PK-parameters
Creatinine (serum, urine, clearance), blood urea nitrogen, phosphorus
Urinary MCP-1:creatinine ratio, and other serum and urinary markers of renal function and inflammation

E.5.2.1

Timepoint(s) of evaluation of this end point

HbA1c on day 84/85 and 113
PK-parameters on day 14 and 15
Renal function and markers on day 8, 15, 29, 57, 85, and 113
Day 1 being the first day of administration

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

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

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

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

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

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