Clinical Trials Register

Summary
EudraCT Number:	2012-001246-17
Sponsor's Protocol Code Number:	CBX129801-DN-201
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:	2012-12-17
Trial 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

2012-001246-17

A.3

Full title of the trial

A Phase 2b, Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Safety and Efficacy of CBX129801 (Ersatta™), Long-Acting Synthetic C-Peptide, in Type 1 Diabetes Mellitus Subjects with Mild to Moderate Diabetic Peripheral Neuropathy

A.3.1

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

A Study to Evaluate Ersatta™ (Long-Acting C-peptide) in Type 1 Diabetes Mellitus Patients with Diabetic Peripheral Neuropathy

A.4.1

Sponsor's protocol code number

CBX129801-DN-201

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01681290

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	Cebix Incorporated
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	Cebix US
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	Cebix Incorporated
B.5.2	Functional name of contact point	Director, Clinical Operations
B.5.3	Address:
B.5.3.1	Street Address	12520 High Bluff Drive, Suite 380
B.5.3.2	Town/ city	San Diego
B.5.3.3	Post code	92130
B.5.3.4	Country	United States
B.5.4	Telephone number	001858729-6505
B.5.5	Fax number	001858729-0620
B.5.6	E-mail	mark@cebix.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	Ersatta
D.3.2	Product code	CBX129801
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not requested
D.3.9.1	CAS number	1350661-05-0
D.3.9.3	Other descriptive name	CBX129801
D.3.9.4	EV Substance Code	SUB90877
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.7
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.IMP: 2
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	Ersatta
D.3.2	Product code	CBX129801
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not requested
D.3.9.1	CAS number	1350661-05-0
D.3.9.3	Other descriptive name	CBX129801
D.3.9.4	EV Substance Code	SUB90877
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	8.0
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	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Mild to moderate diabetic peripheral neuropathy

E.1.1.1

Medical condition in easily understood language

Diabetic peripheral neuropathy

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

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 assess the efficacy of subcutaneously administered CBX129801 in type 1 diabetes mellitus subjects with mild to moderate diabetic peripheral neuropathy.

E.2.2

Secondary objectives of the trial

To assess the efficacy of CBX129801 by evaluating neurophysiological changes over time, the clinical value of CBX129801 therapy, the safety and tolerability of CBX129801, the population pharmacokinetic profile of CBX129801, and the immunogenicity of CBX129801.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Give informed consent;
18 - 65 years old;
Have type 1 diabetes mellitus for a minimum of 5 years (or 4 years with Investigator and Sponsor documented approval, based on patient’s presentation at screening), with a stable diabetic regimen (for at least 3 months) that provides adequate glucose control;
Have clinical signs of diabetic peripheral neuropathy at screening;
Have abnormal sural nerve conduction bilaterally during screening;
Be C-peptide deficient;
Be in good general health (besides having type 1 diabetes mellitus);
Practice effective contraception during the study and for 12 weeks after study participation;
Have a body mass index (BMI) ≥18.0 and <35.0 kg/m2.

E.4

Principal exclusion criteria

Any significant cardiovascular, hematological, lymphatic, immunologic, urologic, dermatologic, psychiatric, renal, hepatic, pulmonary, endocrine (except for diabetes mellitus), central nervous, gastrointestinal, or other major disease;
Any condition that could mimic diabetic peripheral neuropathy or impair peripheral nerve function;
Known or suspected hypersensitivity or allergic reaction to C-peptide or any of the excipients in CBX129801;
Have unstable or inadequate glucose control;
Any significant clinical laboratory value at screening;
Occurrence of a severe, unexplainable hypoglycemic event (defined as requiring the assistance of another individual) within 6 months of the first dose of study drug, or recurrent episodes of non-severe hypoglycemia (≥ 3 per week on average) that are deemed clinically significant by the Investigator;
Have had an islet cell, kidney, and/or pancreas transplant;
If female, is pregnant or lactating;
History of alcohol or substance abuse within 2 years;
Positive screen for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV);
Initiation of treatment or change of dose of medications that could affect peripheral nerve function within 60 days;
Previous treatment with CBX129801 or unmodified C-peptide;
Receipt of an investigational product or therapeutic device, or participation in a drug research study within a period of 30 days;
Chronic use of oral steroids within 60 days.

E.5 End points

E.5.1

Primary end point(s)

Bilateral change from baseline to 52 weeks in initial sensory nerve conduction velocity (SNCVi) in the sural nerve

E.5.1.1

Timepoint(s) of evaluation of this end point

SNCVi baseline assessed during screening prior to initial dose and at Week 52 (or at early termination)

E.5.2

Secondary end point(s)

• Neurophysiological changes from baseline will be assessed for the following endpoints:
- Vibration Perception Threshold (VPT) measured bilaterally in the lower limbs at the great toe at 26 and 52 weeks
- Clinical composite scoring system (modified Toronto Clinical Neuropathy Score [mTCNS]) at 26 and 52 weeks
- Other electrophysiological endpoints:
* Bilateral initial Motor Nerve Conduction Velocity (MNCVi) in the peroneal motor nerve at 26 and 52 weeks
* Bilateral SNCVi and peak sensory nerve conduction velocity (SNCVp) in the sural nerve at 26 weeks
* Bilateral SNCVp in the sural nerve at 52 weeks
* Bilateral peroneal motor nerve distal latency at 26 and 52 weeks
* Amplitudes of the peroneal motor and sural sensory nerve action potentials at 26 and 52 weeks

The endpoint to demonstrate the effects of CBX129801 therapy on painful diabetic peripheral neuropathy (DPN) is:
- Change in pain intensity assessment (11 point scale) between baseline and 52 weeks

• The endpoint to demonstrate the clinical value of CBX129801 therapy in Type 1 diabetes mellitus (T1DM) subjects with mild to moderate DPN is:
- Change in neuropathic symptoms Quality of Life assessment (NeuroQoL) between baseline and 52 weeks

• The endpoint to assess the population pharmacokinetic (PK) profile of CBX129801 is:
- Plasma concentrations of CBX129801 (the results will be pooled across several studies for analysis)

• The endpoints to assess the safety and tolerability of CBX129801 are:
- The incidence and severity of treatment-emergent adverse events (AEs)
- The incidence and severity of hypoglycemic events (HEs)
- Concomitant medications
- Clinically important changes in safety assessment results (including, as appropriate, vital signs, weight, clinical laboratory tests, electrocardiograms [ECGs], and physical and neurological examinations)

• The endpoint to assess the immunogenicity of CBX129801 is:
- Plasma anti-drug antibody (ADA) to PEGylated C-peptide levels up to Week 52

E.5.2.1

Timepoint(s) of evaluation of this end point

All baseline assessments to be completed during screening prior to initial dose and at the following timepoints, or at early termination as necessary:

Assessed at Week 26:
-SNCVi & p

Assessed at Weeks 26 & 52:
- VPT
- mTCNS
- MNCV in peroneal motor nerve
- Bilateral peroneal motor nerve distal latency
- Amplitudes of peroneal motor and sural sensory nerve action potentials
- Plasma ADA
- Body weight
- Sexual function

Assessed at Week 52:
-SNCVp
- NeuroQoL, Pain Intensity

Assessed at Weeks 4, 16, 26, & 52:
- Plasma concentrations of CBX129801
- Physical examination

Other assessment timepoints:
- ECG at Weeks 4, 16, & 52
- Clinical labs at Weeks 4, 8, 16, 26, 39, & 52
- Vital signs at Weeks 2, 4, 8, 16, 26, 39, & 52

Reported throughout study:
- AEs
- HEs

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

Yes

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

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

Canada

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 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:

234

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

240

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)

None

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

2013-02-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-05-28

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-12-02

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