Part 1Primary ObjectiveTo evaluate the local and systemic safety and tolerability of INM-755 cream following repeated once-daily topical applications for 14 days on healthy skin of healthy volunteersSecondary ObjectiveTo assess the local and…
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Tolerability / safety endpoints for Part 1 Objectives
* Incidence of local and systemic treatment-emergent adverse events (TEAEs)
* Changes in vital signs, ECG, safety laboratory tests, erythema, and local
tolerability assessment
Pharmacokinetic endpoints for Part 1 Objectives
* Measurement of plasma concentrations of INM-755.
* Measurement of skin concentration of INM-755.
Secondary outcome
Additional endpoints for Part 1 Objectives
* Change from baseline over time in Bond-Lader visual analogue scale (Mood
Rating Scale) (BL-VAS) and Bowdle VAS (B-VAS)
Wound Healing Endpoints for Part 2 Objective
* Wound characteristics by LSCI, OCT, TEWL and 3D photographyand
* Wound closure over time
Background summary
Epidermolysis Bullosa (EB) is a rare inherited disorder characterized by
mechanical stress-induced blistering of the skin and mucous membranes. EB is
classified into four major types, namely, EB simplex (EBS), junctional EB
(JEB), dystrophic EB (DEB), and Kindler syndrome. Tissue separation occurs in
the epidermis, lamina lucida, or in the sublamina densa (1). The overall
incidence and prevalence of EB is estimated to be 19 per million live births
and approximately 11 per million, respectively (2).
Cutaneous wound healing is a complex process with four main phases:
inflammation, re-epithelialization, tissue formation, and tissue remodeling. In
EB wounds, all four phases of cutaneous wound healing can be impaired, leading
to chronic non-healing wounds. Persistent inflammatory activity, which may
occur with infection or re-injury (e.g., from ongoing friction with clothing or
due to pressure from sitting, and leaning back in chairs), often interferes
with healing of EB wounds (3).
In addition to a persistent inflammatory response, half of the EBS patients
suffer from a mutation in the K14 gene. Basal keratin 14 forms a complex with
keratin 5 providing strength and flexibility to basal keratinocytes and helps
in the formation of hemidesmosomes (4). A desirable outcome for a treatment for
all subtypes of EB would be enhanced skin integrity to prevent new wounds from
forming in combination with anti-inflammatory properties.
INM-755 is being developed for dermal application and treatment of medical
indications characterized by inflammation, pain, and itching. The first
clinical indication under development is EB. INM-755 is a cream containing
cannabinol (CBN) as the active substance. CBN occurs naturally as a trace
component of cannabis, or as a degradation product of *9-tetrahydrocannabinol
(THC). CBN is a weak agonist for the Cannabinoid-1 (CB1) and Cannabinoid-2
receptor (CB2) (5).
Study objective
Part 1
Primary Objective
To evaluate the local and systemic safety and tolerability of INM-755 cream
following repeated once-daily topical applications for 14 days on healthy skin
of healthy volunteers
Secondary Objective
To assess the local and systemic exposure of INM-755 following repeated
once-daily topical applications of INM-755 cream for 14 days on healthy skin of
healthy volunteers
Additional Objectives
To evaluate the subjective feeling effects of INM-755 cream following repeated
once-daily topical applications for 14 days on healthy volunteers
Part 2
To characterize the natural progression of suction blister wound healing on
untreated healthy skin
Study design
This study is a Phase I, double-blind, randomized, vehicle-controlled,
single-center study in healthy volunteers. A total of approximately 22 subjects
will be included.
Intervention
INM-755 cream (high concentration, 0.3%), INM-755 cream (low concentration,
0.03%), or matching vehicle.
Study burden and risks
Benefit
There are no anticipated benefits for subjects participating in the Phase 1
study, other than the benefit of medical evaluation at screening and throughout
the study.
Risk
Small skin punch biopsies are frequently performed in both clinical care and
clinical research. Skin
punch biopsies of 3 mm and 4 mm are considered minimally invasive since the
wound surface is
limited and wound care does usually not involve sutures. The induced wounds
heal quickly and do
not cause tremendous scarring. Subjects with a high risk for hypertrophic
scarring will be excluded.
Suction blisters will be induced on the untreated skin of 12 subjects for
exploratory wound healing characterization. The suction blister device (NP-4,
Electric Diversities, Maryland, USA) is widely used in dermatological research
settings. This device does not qualify as a medical device according to the
Medical Devices Act, see the CCMO website (*An instrument intended by the
manufacturer to be used specifically for diagnostic or therapeutic purposes*).
By using negative pressure (up to 8 in/Hg), the device induces a 10mm diameter
blister in approximately 60 to 90 minutes. The blister formation process is not
painful. Once the blister is formed the roof is pierced with a needle and the
blister fluid is aspirated. Then the blister roof, i.e. epidermal sheet will be
harvested. Blister wounds will be treated with non-adhesive gauze dressing
followed by no treatment after 24h.Complications of the blister include
infection (rare) and post inflammatory hyperpigmentation. To minimize the risk
of hypertrophic scaring, volunteers with a positive medical history will be
excluded. In addition, to mitigate the risk of post inflammatory
hyperpigmentation Fitzpatrick skin types 4-6 are excluded (see Appendix A for
explanation of Fitzpatrick types).
All other quality, pharmacology and toxicology data, and satisfactory safety
and tolerability data demonstrated in nonclinical studies are considered
sufficient to initiate this study.
The risk to subjects in this trial will be minimized by compliance with the
eligibility criteria, proper study design, and close monitoring.
West Hastings St 310-815
Vancouver BC V6C 1B4
CA
West Hastings St 310-815
Vancouver BC V6C 1B4
CA
Listed location countries
Age
Inclusion criteria
1. Male or female subject between 18 and 45 years of age inclusive at the time
of consent.
2. Body mass index (BMI) between 18 and 30 kg/m2, inclusive
3. Subject is in good general health, according to the investigator*s judgment
based on vital signs, medical history, physical examination, and laboratory
tests performed.
4. Contraception:
a. Male participants:
i. A male participant who agrees to follow the contraceptive guidance during
their participation in this study from at least 4 weeks before Day 1 until at
least 4 weeks after the last study product administration. Effective
contraceptive methods are described in the protocol
b. Female participants:
i. A female participant is eligible to participate if she is not pregnant, does
not plan to become pregnant during the study, not breastfeeding, and at least 1
of the following conditions applies:
1. Not a woman of child-bearing potential (WOCBP)
OR
2. A WOCBP who agrees to follow the contraceptive guidance during their
participation in this study from at least 4 weeks before Day 1 until at least 4
weeks after the last study product administration. Effective contraceptive
methods are described in Section 4.5.1.
5. Female subject has had a negative urine pregnancy test at screening and at
Day 1 before dosing.
6. Subject is willing to participate and is capable of giving informed consent.
7. Subjects must be willing to comply with all study procedures, have the
ability to communicate well with the investigator in the Dutch language and
must be available for the duration of the study.
8. Subject has sufficient application area of healthy intact skin of the back.
Exclusion criteria
A subject who meets any of the following criteria at screening and at Day 1
before dosing, unless specified otherwise, will be excluded from participation
in this study:
1. Subject is a female who is breastfeeding, pregnant, or who is planning to
become pregnant during the study.
2. Subject has a history of skin disease or presence of skin condition that, in
the opinion of the investigator, would interfere with the study assessments.
3. Subject has presence of or has a history of atopic dermatitis or psoriasis.
4. Any known allergy or hypersensitivity to medical adhesives (e.g., Tegaderm)
used in this study or any component of the study product (e.g. Poloxamers,
Lecithin, Isopropyl Palmitate).
5. Subject has presence of any tattoos, scratches, open sores, excessive hair,
or skin damages in the target treatment area(s) that, in the opinion of the
investigator, may interfere with study evaluations.
6. Subject has a Fitzpatrick*s Skin Phototype *4.
7. Subject is known to have immune deficiency or is immunocompromised.
8. Subject has a known history of chronic infectious disease (eg, hepatitis B,
hepatitis C, or infection with human immunodeficiency virus).
9. Subject has a history of cancer or lymphoproliferative disease within 5
years prior to Day 1. Subjects with successfully treated nonmetastatic
cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in
situ of the cervix are not to be excluded.
10. Subject had a major surgery within 8 weeks prior to Day 1 or has a major
surgery planned during the study.
11. Subject has any clinically significant medical condition or physical,
laboratory, ECG, or vital signs abnormality that would, in the opinion of the
investigator, put the subject at undue risk or interfere with interpretation of
study results.
12. Subject has used any systemic treatment that could be immunosuppressive
(including oral corticosteroids, oral retinoids, immunosuppressive medication,
methotrexate, cyclosporine, or apremilast) within 4 weeks prior to Day 1. Note:
Intranasal corticosteroids and inhaled corticosteroids are allowed. Eye and ear
drops containing corticosteroids are also allowed.
13. Subject has had excessive sun exposure, is planning a trip to a sunny
climate, or has used tanning booths within 4 weeks prior to Day 1 or is not
willing to minimize natural and artificial sunlight exposure during the study.
Use of sunscreen products (except on application areas) and protective apparel
are recommended when sun exposure cannot be avoided.
14. Subject has received laser treatment, electrolysis on the application areas
within 4 weeks prior to Day 1 or is planning to during the study period.
15. Subject has shaved the application area 72 hours prior to Day 1, or is
planning to do so during the study period.
16. Subject has used cannabis or any cannabinoid products within 12 weeks prior
to Day 1.
17. Subject has used any medication known to impair alertness and/or ability to
detect discomfort within 1 week prior to Day 1.
18. Subject has used a topical applied treatment on the targeted application
area(s) within 1 week prior to Day 1.
19. Subject has a known history of clinically significant drug or alcohol abuse
in the last year prior to Day 1.
20. Subject has a positive screen result for drug of abuse at screening and at
Day 1 before dosing.
21. Subject is unwilling to avoid contact with water on the treatment condition
area(s) during the treatment period.
22. Subject is requiring frequent use of pain medication (e.g., acetaminophen
or NSAIDs) to relieve chronic pain (e.g., frequent headaches, migraines,
dysmenorrhea, arthritis).
23. Subject has a history of hypertrophic scarring or keloid formation in scars
or suture sites.
24. Subject has taken anticoagulant medication, such as heparin, low molecular
weight (LMW) heparin, warfarin, antiplatelets (except low-dose aspirin *81 mg
which will be allowed), within 2 weeks prior to Day 1, or has a
contraindication to skin biopsies .
25. Loss or donation of blood over 500 mL within 12 weeks prior to screening
26. Participation in any marketed or investigational drug or device study
within 12 weeks or 5 half-lives (whichever is longer) prior to first dosing.
27. Subject has a history of an allergic reaction or significant sensitivity to
lidocaine or other local anesthetics.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
Register | ID |
---|---|
EudraCT | EUCTR2019-004093-25-NL |
CCMO | NL71806.056.19 |
OMON | NL-OMON28642 |