Tolerability and Bioavailability of the P144 Peptide Inhibitor of TGF-β1 After Topical Administration in Healthy Volunteers

NCT00656825 | Completed Phase 1

• 2 other identifiers: NAFB001-SS-012006-002755-33
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

Transforming growth factor-beta 1 (TGF-β1) is consistently over expressed in most fibrotic diseases and displays a variety of profibrotic effects in fibroblasts. Activation of TGF-β receptors induces the activation of several kinase signalling cascades leading to the phosphorylation of SMAD proteins as well as to the activation of SMAD-independent kinases that collectively activate ECM synthesis and fibroblast growth and differentiation into myofibroblasts. TGF-β1 is one of the main mediators in the fibrotic process, associated to both scarring and a long list of pathologies related to chronic inflammation and which affect all type of organs and tissues. An increase in TGF-β1 mRNA and protein levels has been described in these processes. Peptide 144 (P144) is the acetic salt of a 14mer peptide from human TGF-β1 type III receptor (betaglycan). P144 TGF-β1-inhibitor has been specifically designed to block the interaction between TGF-β1 and TGF-β1 type III receptor, thus blocking its biological effects. P144 has shown significant antifibrotic activity in mice receiving repeated subcutaneous injections of bleomycin, a widely accepted animal model of human scleroderma, and could contribute to the development. The purpose of this study is to assess the tolerability and safety of topical application of P144 in healthy volunteers.

Conditions

Healthy

Keywords

P144; TGF-β1; Healthy volunteers; Cutaneous tolerability; Skin fibrosis; systemic scleroderma; systemic sclerosis; Safety

Outcome Measures

Primary Outcomes (1)

• Tolerability evaluation was performed through the specific cutaneous tolerability visual scale of Frosch and Kligman.

  Twenty-one days

Secondary Outcomes (1)

• Safety assessment was carried out by studying vital signs, physical examination, by performing laboratory tests, electrocardiogram and reporting any adverse events experienced. Bioavailability of P 144 in serum.

  Twenty-one days

Study Arms (4)

Panel I

ACTIVE COMPARATOR

The first 12 subjects will be selected and ranodmized in order to receive the first treatment dose of 100 μg/mL or placebo in a 8:4 ratio

Drug: P144 cream

Panel II

ACTIVE COMPARATOR

The second 12 subjects will be selected and randomized in order to receive the second treatment dose of 200 μg/mL or placebo in a 8:4 ratio

Drug: P144 cream

Panel III

ACTIVE COMPARATOR

The third 12 subjects will be selected and randomized in order to receive the third treatment dose of 300 μg/mL or placebo in a 8:4 ratio

Drug: P144 cream

Placebo

PLACEBO COMPARATOR

Patients from each panel will be given placebo in a 4:8 ratio.

Drug: Placebo

Interventions

P144 cream DRUG

P144 cream will be given at a dose of 100 μg/mL

Panel I

Placebo DRUG

Placebo will be randomly given to 4 subjects in each panel

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Capable of understanding and willing to provide signed and dated written voluntary informed consent before any protocol specific procedures are performed.
• Age between 18 and 45 years old
• Skin phenotype I to IV following Fitzpatrick's classification scale
• BMI between 20-29 kg/sqm
• Not clinically relevant alterations in: arterial pressure, cardiac frequency, analytical values (Hematology, Biochemistry, Urianalysis, Coagulation, Serology, Toxics)

You may not qualify if:

• Pregnany or lactancy
• Allergy to any medication
• Subjects with skin illnesses or systemic illnesses with skin afectation
• History of drug abuse or regular consumption of alcohol
• Participation in other clinical trials 3 months before the signature of the informed consent
• UV exposure or sun exposure on the zone to be treated
• History of skin hypersensitivity
• Chronic treatment with anti-inflammatories or anti-histaminics
• Treatment with corticoids on the previous month
• Hyperpigmentation on the zone to be treated

Sponsors & Collaborators

• ISDIN: lead
• Digna Biotech S.L.: collaborator

Study Sites (2)

Hospital Universitario Puerta de Hierro

Madrid, Madrid, 28035, Spain

Location

Clínica Universitaria de Navarra

Pamplona, Pamplona, 31008, Spain

Location

MeSH Terms

Conditions

Scleroderma, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Belén Ruiz, MD

  Hospital Universitario Puerta de Hierro

  PRINCIPAL INVESTIGATOR

• Belén Sádaba, MD

  Clínica Universitaria de Navarra

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: April 7, 2008
• First Posted: April 11, 2008
• Study Start: March 1, 2007
• Primary Completion: June 1, 2007
• Study Completion: June 1, 2007
• Last Updated: November 5, 2008

Record last verified: 2008-11

Locations

ES (2)