COMET2: Phase 3b Study of Metvix NDL-PDT Versus Metvix c-PDT in Subjects With Actinic Keratoses

• Sponsor: Galderma R&D (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01821391
• Collaborator: (none)
• Enrollment: 131
• Locations: 18
• Arms: 2
• Duration (Months): 8
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This study was to be conducted as a multi-centre, randomized, investigator-blinded, active and vehicle-controlled, intra-individual (split-face/scalp) non-inferiority (regarding efficacy) and superiority (regarding pain) study.

The primary purpose of this study is to demonstrate the non-inferiority of NDL-PDT compared to c-PDT in terms of lesion complete response rate.

Condition or Disease	Intervention/Treatment	Phase
Actinic Keratoses	Drug: NDL-PDT; Drug: c-PDT; Drug: placebo c-PDT	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 131 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Intervention Model Description: 2 intra-individual groups: Metvix NDL-PDT / Metvix c-PDT Metvix NDL-PDT / Placebo c-PDT2 intra-individual groups: Metvix NDL-PDT / Metvix c-PDT Metvix NDL-PDT / Placebo c-PDT
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: Multi-centre, Randomized, Investigator-blind, Intra-individual Active and Vehicle-controlled Study, Comparing Metvix Natural Daylight Photodynamic Therapy Versus Metvix Conventional Photodynamic Therapy in Subjects With Actinic Keratosis
• Study Start Date: Jul 1, 2013
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NDL-PDT/c-PDT Metvix natural daylight photodynamic therapy and Metvix conventional photodynamic therapy	Drug: NDL-PDT; Metvix natural daylight photodynamic therapy; Other Names: Metvix NDL-PDT ; Drug: c-PDT; Metvix conventional photodynamic therapy; Other Names: Metvix c-PDT
Experimental: NDL-PDT/placebo c-PDT Metvix natural daylight photodynamic therapy and Metvix-placebo conventional photodynamic therapy	Drug: NDL-PDT; Metvix natural daylight photodynamic therapy; Other Names: Metvix NDL-PDT ; Drug: placebo c-PDT; Metvix placebo conventional photodynamic therapy; Other Names: Metvix placebo c-PDT

Outcome Measures

Primary Outcome Measures

1. Percentage (%) Change From Baseline in Total Lesion Complete Response at Week 12 in Group 1 [Baseline, Week 12]

   The lesion complete response rate was defined as the percentage of pre-existing and treated lesions at Baseline that were assessed as clear (complete disappearance of the lesion, visually and by palpation) at Week 12. New lesions or the lesions in non-complete response were not not considered in the lesion response assessment. This outcome measure was analyzed as an intra-individual comparison between Metvix NDL-PDT on one side of the face/scalp and Metvix vehicle cream (placebo) c-PDT on the contralateral side (Group I).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Clinical diagnosis of mild (Grade 1) and/or moderate (Grade 2) AKs on the face or the scalp on treated areas

• Subject with two symmetrical treated areas half scalps or two half faces excluding ears, chin, bridge of the nose, eyelids and lips inside the vermillion border): no more than a twofold difference in terms of total number of lesions between the two TAs

Exclusion Criteria:

• Subject with clinical diagnosis of at least one severe (Grade 3) AK on treated areas

• Subject with pigmented AK on the treated areas

• Immuno-compromised Subject for idiopathic, disease specific or therapeutic reasons

• Subject with porphyria,

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigative site	Montpellier		France
2	Investigational site	Nantes		France
3	Investigational site	Nice		France
4	Investigational site	Paris		France
5	Investigative site	Rennes		France
6	Investigational site	Aachen		Germany
7	Investigational site	Berlin		Germany
8	Investigational site	Muenster		Germany
9	Investigational site	Recklinghausen		Germany
10	Investigational site	Assen		Netherlands
11	Investigational site	Maastricht		Netherlands
12	Investigational site	Nijmegen		Netherlands
13	Investigational site	Huesca		Spain
14	Investigational site	Madrid		Spain
15	Investigative site	Pamplona		Spain
16	Investigational site	Valencia		Spain
17	Investigational site	Karlskoga		Sweden
18	Investigational site	Norrköping		Sweden

Sponsors and Collaborators

• Galderma R&D

Investigators

• Principal Investigator: Nicole Basset Seguin, PhD, MD, Hopital Saint Louis France
• Principal Investigator: Bibiana Perez Garcia, MD, Hospital Ramón y Cajal Spain
• Principal Investigator: Rianne Gerritsen, PhD, MD, Radboud University, Nijmegen Medical Center The Netherlands
• Principal Investigator: Rolf-Markus Sziemies, PhD, MD, Klinik fur Dermatologie und Allergologie Germany
• Principal Investigator: Ingrid Synnerstad, PhD, MD, Hudmottagningen Sweden

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Galderma R&D
• ClinicalTrials.gov Identifier: NCT01821391
• Other Study ID Numbers: RD.03.SPR.29112
• First Posted: Apr 1, 2013
• Last Update Posted: Feb 18, 2021
• Last Verified: Feb 1, 2018

• Keywords provided by Galderma R&D: actinic keratoses; photodynamic therapy; natural daylight
• Additional relevant MeSH terms: Keratosis, Actinic; Keratosis; Methyl 5-aminolevulinate

Study Results

Participant Flow

Arm/Group Title	Group 1	Group 2
Arm/Group Description	Participants applied single dose of Metvix cream topically followed by NDL-PDT (test treatment) on one half-face/scalp and on the contra-lateral side of face/scalp applied Metvix cream topically followed by c- PDT (active comparator) on Day 0 (Baseline).	Participants applied a single dose of Metvix cream topically followed by NDL-PDT (test treatment) on one half-face/scalp and on the contra-lateral side of face/scalp applied Metvix vehicle cream (placebo) followed by c-PDT on Day 0 (Baseline).
Period Title: Overall Study
STARTED	108	23
COMPLETED	107	23
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Group 1	Group 2	Total
Arm/Group Description	Participants applied single dose of Metvix cream topically followed by NDL-PDT (test treatment) on one half-face/scalp and on the contra-lateral side of face/scalp applied Metvix cream topically followed by c- PDT (active comparator) on Day 0 (Baseline).	Participants applied a single dose of Metvix cream topically followed by NDL-PDT (test treatment) on one half-face/scalp and on the contra-lateral side of face/scalp applied Metvix vehicle cream (placebo) followed by c-PDT on Day 0 (Baseline).	Total of all reporting groups
Overall Participants	108	23	131
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	19 17.6%	2 8.7%	21 16%
>=65 years	89 82.4%	21 91.3%	110 84%
Sex: Female, Male (Count of Participants)
Female	9 8.3%	1 4.3%	10 7.6%
Male	99 91.7%	22 95.7%	121 92.4%
Race (Count of Participants)
White	108 100%	22 95.7%	130 99.2%
Other	0 0%	1 4.3%	1 0.8%
Phototype (Count of Participants)
Phototype I	10 9.3%	1 4.3%	11 8.4%
Phototype II	69 63.9%	17 73.9%	86 65.6%
Phototype III	24 22.2%	3 13%	27 20.6%
Phototype IV	5 4.6%	2 8.7%	7 5.3%
Duration of AK (years) (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.66 (8.07)	6.79 (5.81)	9.15 (7.78)

Outcome Measures

1. Primary Outcome

Title	Percentage (%) Change From Baseline in Total Lesion Complete Response at Week 12 in Group 1
Description	The lesion complete response rate was defined as the percentage of pre-existing and treated lesions at Baseline that were assessed as clear (complete disappearance of the lesion, visually and by palpation) at Week 12. New lesions or the lesions in non-complete response were not not considered in the lesion response assessment. This outcome measure was analyzed as an intra-individual comparison between Metvix NDL-PDT on one side of the face/scalp and Metvix vehicle cream (placebo) c-PDT on the contralateral side (Group I).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included entire population enrolled and randomized. ITT analysis imputed missing data using a worst case approach and considered the lesions with missed lesion response assessment as not responded (ITT/Worst-case) lesions.

Arm/Group Title	Group I: Metvix NDL-PDT	Group I: Metvix c-PDT
Arm/Group Description	Participants applied topically a single dose of Metvix cream followed by NDL-PDT on Day 0 (Baseline).	Participants applied topically a single dose of Metvix cream followed by C-PDT on Day 0 (Baseline).
Measure Participants	108	108
Mean (Standard Deviation) [percentage change from baseline]	68.4 (27.7)	71.5 (27.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group I: Metvix NDL-PDT, Group I: Metvix c-PDT
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.2665
	Comments
	Method	Paired Student's t test
	Comments

Adverse Events

Time Frame	3 months
Arm/Group Title	NDL-PDT		c-PDT		Placebo c-PDT		Unspecific Treated Side
Arm/Group Description	Metvix natural daylight photodynamic therapy treated side		Metvix conventional photodynamic therapy treated side		Placebo conventional photodynamic therapy treated side		AE occuring outside the treated area + systemic AE
All Cause Mortality
	NDL-PDT		c-PDT		Placebo c-PDT		Unspecific Treated Side
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/131 (0%)		0/108 (0%)		0/23 (0%)		1/131 (0.8%)
Serious Adverse Events
	NDL-PDT		c-PDT		Placebo c-PDT		Unspecific Treated Side
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/131 (0%)		0/108 (0%)		0/23 (0%)		6/131 (4.6%)
Cardiac disorders
Cardiac arrest	0/131 (0%)	0	0/108 (0%)	0	0/23 (0%)	0	1/131 (0.8%)	1
Ear and labyrinth disorders
Vertigo	0/131 (0%)	0	0/108 (0%)	0	0/23 (0%)	0	1/131 (0.8%)	1
Gastrointestinal disorders
Haematemesis	0/131 (0%)	0	0/108 (0%)	0	0/23 (0%)	0	1/131 (0.8%)	1
Mallory weiss lesion in oesophagus	0/131 (0%)	0	0/108 (0%)	0	0/23 (0%)	0	1/131 (0.8%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon neoplasia	0/131 (0%)	0	0/108 (0%)	0	0/23 (0%)	0	1/131 (0.8%)	1
Nervous system disorders
Spinal cord compression	0/131 (0%)	0	0/108 (0%)	0	0/23 (0%)	0	1/131 (0.8%)	1
Respiratory, thoracic and mediastinal disorders
PULMONARY OEDEMA/ SUPPOSED WATER IN LUNG	0/131 (0%)	0	0/108 (0%)	0	0/23 (0%)	0	1/131 (0.8%)	1
Other (Not Including Serious) Adverse Events
	NDL-PDT		c-PDT		Placebo c-PDT		Unspecific Treated Side
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	65/131 (49.6%)		66/108 (61.1%)		7/23 (30.4%)		3/131 (2.3%)
Infections and infestations
Rash pustular	1/131 (0.8%)	1	2/108 (1.9%)	2	0/23 (0%)	0	0/131 (0%)	0
Injury, poisoning and procedural complications
Post procedural haemorrage	5/131 (3.8%)	5	4/108 (3.7%)	4	1/23 (4.3%)	1	0/131 (0%)	0
Skin and subcutaneous tissue disorders
Blister	2/131 (1.5%)	2	1/108 (0.9%)	1	0/23 (0%)	0	0/131 (0%)	0
Erythema	31/131 (23.7%)	31	39/108 (36.1%)	39	4/23 (17.4%)	4	1/131 (0.8%)	1
Pain of skin	8/131 (6.1%)	8	11/108 (10.2%)	11	0/23 (0%)	0	0/131 (0%)	0
Photosensitivity reaction	10/131 (7.6%)	10	8/108 (7.4%)	8	1/23 (4.3%)	1	0/131 (0%)	0
Pruritus	13/131 (9.9%)	13	16/108 (14.8%)	16	1/23 (4.3%)	1	1/131 (0.8%)	1
Scab	12/131 (9.2%)	12	16/108 (14.8%)	17	0/23 (0%)	0	1/131 (0.8%)	1
Skin burning sensation	12/131 (9.2%)	12	16/108 (14.8%)	17	0/23 (0%)	0	1/131 (0.8%)	1
Skin erosion	0/131 (0%)	0	5/108 (4.6%)	5	0/23 (0%)	0	0/131 (0%)	0
Skin exfoliation	2/131 (1.5%)	2	4/108 (3.7%)	4	1/23 (4.3%)	1	0/131 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.