Study of PXL01 Versus Placebo to Inhibit Adhesion Formation After Flexor Tendon Surgery (PHSU02)

A Prospective Double-blind, Randomised Concept Study of PXL01 Versus Placebo in Flexor Tendon Surgery

The objectives of the study are to assess efficacy, safety, and handling of PXL01 in patients with flexor tendon injury in zone I or II.

Study Overview

• Status: Completed
• Conditions: Surgical Adhesions
• Intervention / Treatment: Drug: Placebo; Drug: PXL01

Detailed Description

This is a multi-centre, randomized, double blind, parallel study design in patient admitted for flexor tendon repair in zone II.

The patients will undergo 9 visits within the time frame of the study. Patients will be randomized to receive treatment with PXL01 or standard care.

Primary objective is to assess total active motion based on PIP and DIP joints (TAM2) at 12-week visit. Secondary objectives are to assess TAM2 at all time points except for 12 weeks, TAM based on MCP, PIP, and DIP joints (TAM3) at all time points, Total Active Motion in DIP joint (DIPAM), tip-to-crease, grip strength and Total Passive Motion (TPM2 and TPM3).

Before any study-related assessment takes place, patients are given verbal and written information about the study and informed consent is achieved from the patient and/or legal guardian. The study should be carried out in accordance with the Clinical Study Protocol (CSP), ICH guidelines for Good Clinical Practise (GCP), and applicable regulatory requirements.

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Dept. of Hand Surgery, Aalborg Hospital
  • Odense, Denmark, 5000
    • Dept. of Hand Surgery, Odense University Hospital
• Germany
  • Bad Neustadt, Germany, 97616
    • Klinik für Handchirurgie der Herz- und Gefäß-Klinik GmbH
  • Duisburg, Germany, 47166
    • Katholisches Klinikum Duisburg, St. Barbara Hospital, Klinik für Plastische Chirurgie und Handchirurgie
  • Essen, Germany, 45257
    • St.Josef Hospital Essen- Kupferdreh, Abteilung für Handchirurgie
  • Hannover, Germany, 30625
    • Klinik für Plastische, Hand- und Wiederherstellungschirurgie, Medizinische Hochschule Hannover
  • Homburg, Germany, 66421
    • Universitätsklinikum des Saarlandes, Klinik für Unfall-, Hand - und Wiederherstellungschirugie
  • Lübeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Sektion für Plastische Chirurgie, Handchirurgie und Intensiveinheit für Schwerbrandverletzte
  • Munich, Germany, 80336
    • Ludwig-Maximilians Universität München, Klinik und Poliklinik für Plastische Chirurgie und Handchirurgie, Campus Innenstadt
  • Munich, Germany, 81377
    • Ludwig-Maximilians Universität München, Klinik und Poliklinik für Plastische Chirurgie und Handchirurgie, Campus Großhadern
  • Stuttgart, Germany, 70199
    • Klinik für Handchirurgie, Mikrochirurgie und Rekonstruktive Brustchirurgie Vinzenz von Paul Kliniken GmbH
• Sweden
  • Gothenburg, Sweden, SE-413 45
    • Dept. of Hand Surgery Sahlgrenska University Hospital
  • Malmö, Sweden, SE-20502
    • Dept. of Hand Surgery Malmö University Hospital
  • Stockholm, Sweden, 118 83
    • Dept. of Hand Surgery, Stockholm South General Hospital
  • Uppsala, Sweden, SE-75185
    • Dept. of Hand Surgery Uppsala University Hospital, entrance 70

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Complete division of flexor digitorium profundus tendon (FDP) in zone I or II, with or without division of flexor digitorium superficialis (FDS) and possible to rejoin with tendon suture
2. Open flexor tendon injury sutured within 14 days after trauma
3. 12-75 years of age
4. Signed informed consent prior to any study related procedures

Exclusion criteria

1. Treatment with any investigational product within 4 weeks of study entry
2. Patients previously included in the study
3. Thumbs with complete or partial division of flexor pollicis longus (FPL)
4. Concomitant fracture(s) requiring immobilisation
5. Injuries with associated soft tissue loss
6. Severe crush injury
7. Palmar plate injury requiring immobilisation
8. Devascularisation/requirement of vascular repair
9. Joint injuries
10. Bilateral injuries
11. Previous flexor tendon surgery in the digit, which is to be treated with IMP
12. Reduced motion in the digit, which is to be treated with IMP, or the corresponding digit prior to the injury
13. Compliance with mobilisation protocol not expected
14. Alcohol or drug abuse
15. Severe intercurrent illness, which in the opinion of the Investigator, may put the patient at risk when participating in the study, or affect the patient's ability to take part in the study
16. Pregnant or lactating females
17. Fertile women who do not accept the consistent and correct use of highly effective methods of birth control defined as implants, injectables, combined oral contraceptives, intra-uterine device (IUD)s, sexual abstinence or vasectomised partner during the first two weeks post-surgery. A condom alone is not considered an acceptable method for birth control, not even together with spermicide.
18. Known allergy to any component of the study product or placebo

19. Patients suffering from:

    • Diabetes Mellitus patients where significant diabetic complications may delay healing according to the investigator's judgement
    • Rheumatoid arthritis

20. Or patients treated with:

    • Systemic steroids within one month
    • Immunosuppressive drugs within three months
    • Daily use of NSAIDs within one week or occasional use within 8 hours

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo is administered locally between the flexor tendon and the tendon sheath and around the tendon sheath at a volume of 0.5 ml. Administration of the product is carried out after repair of the flexor tendon but before closure of the surgical wound.	Drug: Placebo; Placebo is a physiological sodium chloride solution, which is clear and colourless.
Experimental: PXL01; PXL01 is administered locally between the flexor tendon and the tendon sheath and around the tendon sheath at a volume of 0.5 ml. Administration of the product is carried out after repair of the flexor tendon but before closure of the surgical wound.	Drug: PXL01; PXL01 is a synthetic peptide sequentially derived from human lactoferrin. PXL01 is formulated in a viscous solution of sodium hyaluronate. The drug product is administered locally between the flexor tendon and the tendon sheath and around the tendon sheath at a volume of 0.5 ml. Administration of the product is carried out after repair of the flexor tendon but before closure of the surgical wound.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TAM2	The primary variable is TAM2: The sum of Total Active Motion at the proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints of the affected digit at actively made fist minus the extensor lag at these joints.	At 12 weeks after surgery

Collaborators and Investigators

• Sponsor: Pergamum AB
• Investigators: Principal Investigator: Monica Wiig, MD, PhD, Dept. of Hand Surgery Uppsala University Hospital

Publications and helpful links

General Publications

• Wiig ME, Dahlin LB, Friden J, Hagberg L, Larsen SE, Wiklund K, Mahlapuu M. PXL01 in sodium hyaluronate for improvement of hand recovery after flexor tendon repair surgery: randomized controlled trial. PLoS One. 2014 Oct 23;9(10):e110735. doi: 10.1371/journal.pone.0110735. eCollection 2014.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: November 25, 2009
• First Submitted That Met QC Criteria: November 30, 2009
• First Posted (Estimate): December 1, 2009

Study Record Updates

• Last Update Posted (Estimate): May 29, 2014
• Last Update Submitted That Met QC Criteria: April 30, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Surgical Adhesions; Post-surgical adhesions; Flexor tendon
• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis; Cicatrix; Tissue Adhesions
• Other Study ID Numbers: PHSU02