Clinical Trials Register

Summary
EudraCT Number:	2012-003286-18
Sponsor's Protocol Code Number:	802-247-09-032
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2013-09-16
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

Germany - PEI

A.2

EudraCT number

2012-003286-18

A.3

Full title of the trial

A Phase 3 Randomized Safety and Efficacy Trial of HP802-247 in the Treatment of Chronic Venous Leg Ulcers (EU)

A.3.1

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

Study to find out if the investigational product HP802-247 can help people to treat certain type of leg ulcer

A.4.1

Sponsor's protocol code number

802-247-09-032

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	Smith & Nephew 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	Smith & Nephew 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 Germany GmbH
B.5.2	Functional name of contact point	Medpace Regulatory Submissions
B.5.3	Address:
B.5.3.1	Street Address	Theresienhoehe 30
B.5.3.2	Town/ city	Munich
B.5.3.3	Post code	80339
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4989895571860
B.5.5	Fax number	+49898955718160
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.3.2	Product code	HP802-247
D.3.4	Pharmaceutical form	Cutaneous spray, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	fibroblasts
D.3.9.3	Other descriptive name	GROWTH-ARRESTED FIBROBLASTS
D.3.9.4	EV Substance Code	SUB120984
D.3.10	Strength
D.3.10.1	Concentration unit	ml millilitre(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.45 x 10^6 cells
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Keratinocytes
D.3.9.3	Other descriptive name	GROWTH-ARRESTED KERATINOCYTES
D.3.9.4	EV Substance Code	SUB120985
D.3.10	Strength
D.3.10.1	Concentration unit	ml millilitre(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.05 x 10^6 cells
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
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)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	Yes
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	Cutaneous spray
D.8.4	Route of administration of the placebo	Cutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic venous leg ulcer

E.1.1.1

Medical condition in easily understood language

Leg ulcer

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	LLT
E.1.2	Classification code	10066677
E.1.2	Term	Chronic leg ulcer
E.1.2	System Organ Class	100000004858

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Compare HP802-247 plus compression therapy against Control (Vehicle) plus compression therapy for the proportion of subjects with complete wound closure over the 12-week treatment period from baseline.

E.2.2

Secondary objectives of the trial

KEY: Compare the efficacy of HP802-247 plus compression therapy against Control (Vehicle) plus compression therapy in achieving complete wound closure, based on time in days to closure over the 12-week treatment period from baseline.
SECONDARY (1) Compare HP802-247 plus compression therapy against Control plus compression therapy for the proportion of subjects with complete wound closure at each of the 12 treatment weeks from baseline.
(2) Compare HP802-247 plus compression therapy against Control (Vehicle) plus compression therapy for the proportion of subjects with durable wound healing over the 3 months following complete wound closure achieved over the 12-week treatment period.
(3) For each therapy, compare pain levels reported at each treatment week against baseline pain level for the target wound and target leg.
EXPLORATORY: Compare HP802-247 plus compression therapy against Control (Vehicle) plus compression therapy for differences in Health related Quality of Life (HRQoL).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Provide informed consent.
2. Age of 18 years and above and of either sex.
3. Willing to comply with protocol instructions, including allowing all trial assessments.
4. Men, women not of child-bearing potential, and women of child-bearing potential (those who are not premenarchal, not surgically sterilized [hysterectomy or bilateral oophorectomy], or not post-menopausal), may participate in the trial if they meet all of the following conditions:
• Not breast feeding
• A negative serum pregnancy test at screening
• Agree to undertake a serum pregnancy test upon exiting the trial
• Do not intend to become pregnant during the trial
• Using adequate birth control methods and agree to continue using those methods for the duration of the trial.

Adequate birth control methods are defined as: hormonal— oral, implantable or injectable contraceptives; mechanical—spermicide in conjunction with a barrier such as a condom or diaphragm; IUD; or surgical sterilization of partner.

NOTE: Women who have had a bilateral tubal ligation are not considered to have been surgically sterilized and must agree to the conditions as specified above.

5. Have a venous leg ulcer (VLU) between the knee and ankle (at or above the malleolus), with a surface area ≥ 2.0 cm2 and ≤ 12.0 cm2 confirmed using the ARANZ Silhouette wound imaging and measurement device.
• If the subject presents with > 1, but ≤ 3 venous leg ulcers on the same leg, the largest qualifying ulcer will be selected as the target ulcer.
• A true single target ulcer MUST be at least 1.0 cm from any other VLU and will be used for treatment and evaluation throughout the trial.
• If the target ulcer is less than 1.0 cm from another VLU, the ulcers may be combined and traced as a single target ulcer provided at least one of the ulcers is greater than or equal to 2.0 cm2 in area. The total surface area must be ≤ 12.0 cm2.
6. Venous insufficiency confirmed by duplex Doppler ultrasound examination for valvular or venous incompetence.
• Availability of a complete report of a previous examination performed within 12 months of screening will be acceptable.
7. Arterial supply adequacy confirmed by any one of the following:
• Great toe pressure ≥ 50 mm/Hg
• Systolic blood pressure Ankle Brachial Index (ABI) in the range ≥ 0.8 to ≤ 1.1
• TcPO2 ≥ 40 mmHg from the foot
8. Target ulcer involves a full thickness skin loss, but WITHOUT exposure of tendon, muscle, or bone.
9. Target ulcer duration ≥ 6 weeks but ≤ 104 weeks (24 months).
10. Acceptable state of health and nutrition with pre-albumin levels of ≥ 10 mg/dL (0.10 g/L), serum albumin ≥ 2.0 g/dL (20 g/L), per the Screening central lab report, and no abnormal laboratory values that, in the opinion of the Principal Investigator, place the subject at risk for the trial. Refer to Appendix 18.4 for further details.
11. Per Screening central lab, an HbA1C < 12.0% (108 mmol/mol)
12. Karnofsky score ≥ 60%

E.4

Principal exclusion criteria

1. History of anaphylaxis, serum sickness, or erythema multiforme reaction to aprotinin, bovine serum albumin or bovine serum proteins, penicillin, streptomycin, amphotericin B, Polysorbate 80 or any substance used in the manufacturing of HP802-247 or its vehicle.
2. Prior diagnosis of Systemic Lupus Erythematosus with elevated anti-DNA antibody titers, Buerger’s disease (thromboangiitis obliterans), current diagnosis of vasculitis, or current diagnosis of claudication.
3. Therapy with another investigational agent within thirty (30) days of Screening, or during the trial.
4. A target ulcer of non-venous etiology (e.g., sickle cell anemia, necrobiosis lipoidica diabeticorum, pyoderma gangrenosum, vasculopathic or vasculitic).
5. Deep Vein Thrombosis (DVT) that is acute, defined as the first 10 days from onset of symptoms, or any DVT for which compression bandaging is considered by the Investigator to be contraindicated.
6. Clinical evidence of ulcer bed infection as described in the Study Guide.
7. Documented history of osteomyelitis at the target wound location within 6 months preceding the Screening Visit.
8. Refusal of or inability to tolerate compression therapy.
9. Therapy of the target ulcer with autologous skin graft, Apligraf™, or Dermagraft™ within 30 days preceding the Screening Visit.
10. Therapy of the target ulcer with topical growth factors within 1 week preceding the Screening Visit.
11. Per Screening central lab hematology† report, WBC < 2.0 x 10 (to the power 9)/L, neutrophils < 1.0 x 10 (to the power 9)/L, platelets < 100 x10 (to the power 9)/L, and Hgb < 8.0 g/dL.
12. Per Screening central lab chemistry† report, serum total bilirubin or serum creatinine ≥ 2 times the upper limit of the normal value (ULN); or, aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase ≥ 3 times ULN.
13. Current therapy with systemic antibiotics.
14. Current systemic therapy with cytotoxic drugs.
15. Current therapy with chronic (> 10 days) oral corticosteroids.
16. Current therapy with TNFα inhibitors other than Trental® (pentoxifylline).
17. History of cancer in the preceding 5 years (other than carcinoma in situ of the cervix or adequately treated non-melanoma skin cancers).
18. Any prior exposure to HP802-247 or its vehicle.
Additional Exclusion Criteria Prior to Randomization
19. A rate of healing of the target ulcer by > 0.349 cm during the Run-in period (defined as Run-in Visit 1 to Run-in Visit) 20. Use of excluded concomitant medications or procedures during the Run-in period.
21. A clinically diagnosed infection of the target ulcer requiring treatment.
22. Muscle, tendon, or bone exposure in the target ulcer.
23. Severe uncontrolled edema of the target ulcer leg.
24. In the judgment of the Investigator, the subject is not able to tolerate compression therapy as required by protocol or is not an appropriate trial subject.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint for this trial is the proportion of subjects with “complete wound closure” over the 12-week treatment period, and the time in number of days to complete wound closure during the treatment period.

E.5.1.1

Timepoint(s) of evaluation of this end point

week 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17

E.5.2

Secondary end point(s)

• Time in number of days to complete wound closure during the treatment period.
• The number of subjects with complete wound closure at each of the 12 double-blind treatment weeks and at each of the follow-up visits.
• Pain associated with the target wound and target leg at each of the 12 double-blind treatment weeks, using the PAIN VAS scale

E.5.2.1

Timepoint(s) of evaluation of this end point

week 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17

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

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

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

LPLV

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

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:

264

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

176

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

136

F.4.2

For a multinational trial

F.4.2.1

In the EEA

440

F.4.2.2

In the whole clinical trial

440

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)

After the end of the trial patients will be treated according to their standard treatment in their country.

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

2013-09-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-09-24

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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