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

• Sponsor: Pergamum AB (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01022242
• Collaborator: (none)
• Enrollment: 138
• Locations: 15
• Arms: 2
• Duration (Months): 38
• Patients Per Site: 9.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Surgical Adhesions	Drug: PXL01; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 138 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Prospective Double-blind, Randomised Concept Study of PXL01 Versus Placebo in Flexor Tendon Surgery
• Study Start Date: Dec 1, 2009
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. TAM2 [At 12 weeks after surgery]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. 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

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Pergamum AB

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pergamum AB
• ClinicalTrials.gov Identifier: NCT01022242
• Other Study ID Numbers: PHSU02
• First Posted: Dec 1, 2009
• Last Update Posted: May 29, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by Pergamum AB: Surgical Adhesions; Post-surgical adhesions; Flexor tendon
• Additional relevant MeSH terms: Tissue Adhesions

Study Results

Participant Flow

Arm/Group Title	Placebo	PXL01
Arm/Group Description	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. Placebo: Placebo is a physiological sodium chloride solution, which is clear and colourless.	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. 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.
Period Title: Overall Study
STARTED	70	65
COMPLETED	49	46
NOT COMPLETED	21	19

Baseline Characteristics

Arm/Group Title	Placebo	PXL01	Total
Arm/Group Description	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. Placebo is a physiological sodium chloride solution, which is clear and colourless.	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. 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.	Total of all reporting groups
Overall Participants	70	65	135
Age (Count of Participants)
<=18 years	2 2.9%	4 6.2%	6 4.4%
Between 18 and 65 years	66 94.3%	60 92.3%	126 93.3%
>=65 years	2 2.9%	1 1.5%	3 2.2%
Sex: Female, Male (Count of Participants)
Female	19 27.1%	17 26.2%	36 26.7%
Male	51 72.9%	48 73.8%	99 73.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 2.9%	0 0%	2 1.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 1.4%	1 1.5%	2 1.5%
White	64 91.4%	62 95.4%	126 93.3%
More than one race	0 0%	1 1.5%	1 0.7%
Unknown or Not Reported	3 4.3%	1 1.5%	4 3%

Outcome Measures

1. Primary Outcome

Title	TAM2
Description	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.
Time Frame	At 12 weeks after surgery

Outcome Measure Data

Analysis Population Description

FAS population

Arm/Group Title	Placebo	PXL01
Arm/Group Description	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. Placebo is a physiological sodium chloride solution, which is clear and colourless.	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. 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.
Measure Participants	51	50
Median (Full Range) [Degrees]	108	121

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PXL01
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8861
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Arm/Group Title	Placebo		PXL01
Arm/Group Description	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. Placebo is a physiological sodium chloride solution, which is clear and colourless.		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. 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.
All Cause Mortality
	Placebo		PXL01
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		PXL01
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/70 (12.9%)		10/65 (15.4%)
Cardiac disorders
stroke	0/70 (0%)	0	1/65 (1.5%)	1
Immune system disorders
myeloproliferative disorder	0/70 (0%)	0	1/65 (1.5%)	1
Injury, poisoning and procedural complications
procedural pain	0/70 (0%)	0	1/65 (1.5%)	1
allergic urticaria	0/70 (0%)	0	1/65 (1.5%)	1
accidental death	0/70 (0%)	0	1/65 (1.5%)	1
Musculoskeletal and connective tissue disorders
Tendon rupture	6/70 (8.6%)	6	5/65 (7.7%)	5
adhesion (resulting in tenolysis)	2/70 (2.9%)	2	1/65 (1.5%)	1
Nervous system disorders
syncope	1/70 (1.4%)	1	0/65 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		PXL01
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/70 (31.4%)		22/65 (33.8%)
General disorders
Oedema peripheral	4/70 (5.7%)	5	5/65 (7.7%)	5
Infections and infestations
Nasopharyngitis	8/70 (11.4%)	8	7/65 (10.8%)	8
Localised Infections	2/70 (2.9%)	2	4/65 (6.2%)	4
Musculoskeletal and connective tissue disorders
Pain in extremity	6/70 (8.6%)	6	2/65 (3.1%)	2
Nervous system disorders
Headache	2/70 (2.9%)	2	4/65 (6.2%)	4

Limitations/Caveats

High drop out rate leading to a low number of subjects analyzed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.