KM-001 Cream for Treatment of Pruritus in Adult Patients With Lichen Simplex Chronicus (LSC)

NCT05454462 | Completed Phase 1 DMC

• 1 other identifier: KM-001AB1
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase 1, multi-center, randomized, vehicle-controlled, double-blinded, parallel-group study. Approximately 6 sites will conduct the study at Germany. Approximately 61 patients (male and female) planned to be screened. 51 patient planned to be randomized. Patients will be randomized to 1 of 3 treatment arms (KM-001 0.3%, KM-001 1%, or vehicle cream) iina a ration of 1:1:1 Patient's duration of participation will be up to 7 weeks,

• a screening period with 1 visit (Visit 1) within up to 14 days (Days -14 to -1),
• a 4-week treatment period with 3 visits (Visit 2 on Day 0, Visit 3 on Day 7, Visit 4 at Day 28 and 2 phone calls on Days 14 and 21, and
• a 1-week follow-up period with 1 visit (Visit 5 on Day 35), as well as unscheduled visits as needed Since KM-001 is tested in humans for the first time, the safety of KM-001 will be evaluated in a subgroup of 6 patients (sentinel group) at selected sites prior to screening of the remaining sites. Efficacy assessments will include subjective assessments of itch and investigator assessment of the treatment effect on LSC target lesion using scoring systems. Safety parameter (including physical examination, vital signs, ECG, standard laboratory test, and PK analysis) will be monitored from the signing of the informed consent form (ICF) until the last follow-up visit. Recording of AEs and serious AEs (SAEs) will be done throughout the study with special attention to local AEs in the treatment area (LSC target lesion, dermal safety).

Conditions

Lichen Simplex Chronicus

Outcome Measures

Primary Outcomes (16)

• Safety endpoint - Will be assessed through collection and analysis of adverse events

  Incidence of treatment-emergent adverse events (AEs) and serious adverse events (SAEs)

  up to 7 weeks

• Safety endpoint-Hematology blood test

  RBC, WBC and platelets count, absolute neutrophils, lymphocytes, monocytes, eosinophil and basophil counts, reticulocyte count, hemoglobin, hematocrit, MCV and MCH will be tested and assess. The assessment will be compared thr baseline results. Exceptional values above the normal or below the normal will indicate an aggravation of the participant's condition

  up to 7 weeks

• Safety endpoint- Serology blood test - HBV

  HBsAb,HBsAg, HBcAb will be prformed at screening visit. laboratory measurements will be assessed and listed.

  up to 14 days

• Safety endpoint- Serology blood test- Hepatits C

  Hepatits C virus antibody will be prformed at screening visit. laboratory measurements will be assessed and listed.

  up to 14 days

• Safety endpoint- Serology blood test- HIV

  HIV will be prformed at screening visit. laboratory measurements will be assessed and listed.

  up to 14 days

• Safety endpoint-Chemistry

  Chemistry measurements will be presented descriptively by visit including changes from baseline for quantitative outcomes. Shift tables showing changes with respect to the normal range between baseline and each post-baseline visit will be shown. Incidence of any laboratory outcome of clinical significance will be shown for scheduled and unscheduled measures, including a presentation for each laboratory parameter.

  up to 7 weeks

• Safety endpoin-Urine tests

  Specific gravity, pH, glucose, protein, blood and ketones by will perform by dipstick. assessment will be compared to the normal range. Change from baseline (Day -14 to -1 \[screening/Visit 1\]) in safety laboratory parameters at Day 7 (Visit 3 or ETV) and Day 28 (Visit 4 or ETV)

  up to 7 weeks

• Safety endpoin-Pregnancy test

  In women of child-bearing potential only. At all the on-site visits serum beta-human chorionic gonadotropin (b-hCG) concentration will be tested.

  up to 7 weeks

• Safety endpoin-Vital signs- Pulse

  units: BPM (beats per minute) Data management team will assess and review the vital signs. The category of the assessments will be compared to the normal ranges. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition

  up to 7 weeks

• Safety endpoin-Vital signs- Blood pressure

  units: blood pressure \[mm Hg\]. Data management team will assess and review the vital signs. The category of the assessments will be compared to the normal ranges. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition

  up to 7 weeks

• Safety endpoin-Vital signs- Body temperature

  body temperature will be assesed and the changes from the baseline. units:Celsius degrees. Data management team will assess and review the vital signs. The category of the assessments will be compared to the normal ranges.

  up to 7 weeks

• Safety endpoin-Electrocardiogram

  A 12-lead, resting, digital ECG will be taken for each participant at Screening and on Day 28 or at ETV. the following ECG parameters will be recorded: heart rate (HR), PR, QT and QRS intervals and QTC. Resting ECG parameter and changes from baseline will be assesed

  up to 7 weeks

• Safety endpoin-Physical examination

  A complete examination will be performed at screening and baseline: As a minimum, the following body systems will be examined and listed: basic status of the main organ systems (ear nose throat, heart, lungs, abdomen, neurological status) as well as physical examination of the skin. An abbreviated examination including a comprehensive skin examination will be performed at other indicated visits. Height and weight measurement will be performed at screening only.

  up to 4 weeks

• KM-001 plasma levels (PK) - Cmax

  CMAX measurement (mg/ml)

  Up to 5 weeks

• KM-001 plasma levels (PK) - Tmax

  Tmax measurement (h)

  Up to 5 weeks

• KM-001 plasma levels (PK) - AUC 0-t

  AUC measurement (mg\*h/L)

  Up to 5 weeks

Secondary Outcomes (3)

• Efficacy endpoint will be assessed through collection and analysis of lesion Assessment-IGA

  up to 7 weeks

• Efficacy endpoint will be assessed through collection and analysis of lesion Assessment- (PP-NRS)

  up to 7 weeks

• Efficacy endpoint will be assessed through collection and analysis of lesion Assessment- (PP-NRS)- responders

  up to 7 weeks

Study Arms (3)

KM-001 0.3%

EXPERIMENTAL

KM-001 0.3% cream will be applied to the affected area twice daily for 4 consecutive weeks.

Drug: IMP Application KM-001; Diagnostic Test: Chemistry; Diagnostic Test: Hematology; Diagnostic Test: Urinalysis; Diagnostic Test: Serelogy; Diagnostic Test: 12-Lead ECG; Diagnostic Test: Pregnancy test; Diagnostic Test: Blood PK sampling; Procedure: Physical Examination; Procedure: Vital signa; Diagnostic Test: Investigator's Global Assessment; Diagnostic Test: Itch Assessment via PP-NRSj; Other: E-diary data

KM-001 1%

EXPERIMENTAL

KM-001 0.3% cream will be applied to the affected area twice daily for 4 consecutive weeks.

Drug: IMP Application KM-001; Diagnostic Test: Chemistry; Diagnostic Test: Hematology; Diagnostic Test: Urinalysis; Diagnostic Test: Serelogy; Diagnostic Test: 12-Lead ECG; Diagnostic Test: Pregnancy test; Diagnostic Test: Blood PK sampling; Procedure: Physical Examination; Procedure: Vital signa; Diagnostic Test: Investigator's Global Assessment; Diagnostic Test: Itch Assessment via PP-NRSj; Other: E-diary data

Vehicle arm

PLACEBO COMPARATOR

Vehicle cream will be applied to the affected area twice daily for 4 consecutive weeks.

Drug: IMP Application KM-001; Diagnostic Test: Chemistry; Diagnostic Test: Hematology; Diagnostic Test: Urinalysis; Diagnostic Test: Serelogy; Diagnostic Test: 12-Lead ECG; Diagnostic Test: Pregnancy test; Diagnostic Test: Blood PK sampling; Procedure: Physical Examination; Procedure: Vital signa; Diagnostic Test: Investigator's Global Assessment; Diagnostic Test: Itch Assessment via PP-NRSj; Other: E-diary data

Interventions

IMP Application KM-001 DRUG

KM-001 will be supplied in glass jars (30 ml) and will be provided to patients with spatulas and polyethylene gloves on all the clinical visits. the patient will use IMP twice a day for 28 days.

Also known as: Experimental drug administration

KM-001 0.3%; KM-001 1%; Vehicle arm

Chemistry DIAGNOSTIC_TEST

patients will provide a blood sample for a chemistry blood test on days -14 (screening visit), Day 7(visit 3), day 28 (end of treatment) or at ET visit.

Also known as: Blood test

KM-001 0.3%; KM-001 1%; Vehicle arm

Hematology DIAGNOSTIC_TEST

patients will provide a blood sample for a hematology blood test on days -14 (screening visit), Day 7(visit 3), day 28 (end of treatment) or at ET visit.

Also known as: Blood test

KM-001 0.3%; KM-001 1%; Vehicle arm

Urinalysis DIAGNOSTIC_TEST

Patients will provide a blood sample for a urine test on days -14 (screening visit), Day 7(visit 3), day 28 (end of treatment) or at ET visit.

Also known as: Urine test

KM-001 0.3%; KM-001 1%; Vehicle arm

Serelogy DIAGNOSTIC_TEST

Patients will provide a blood sample for serelogy test at day -14 (screening visit)

Also known as: Blood test

KM-001 0.3%; KM-001 1%; Vehicle arm

12-Lead ECG DIAGNOSTIC_TEST

patients will undergo an ECG examination on days -14 (screening visit), and day 28 (end of treatment visit).

KM-001 0.3%; KM-001 1%; Vehicle arm

Pregnancy test DIAGNOSTIC_TEST

Women of child-bearing potential only will provide at all the on-site visits b-hCG concentration will be tested

Also known as: Blood test

KM-001 0.3%; KM-001 1%; Vehicle arm

Blood PK sampling DIAGNOSTIC_TEST

PK test will be performed on day 1, 7, 28, 35 and on ET visit

KM-001 0.3%; KM-001 1%; Vehicle arm

Physical Examination PROCEDURE

patients will undergo a physical examination on all the clinical visits

KM-001 0.3%; KM-001 1%; Vehicle arm

Vital signa PROCEDURE

patient's vital signs will be measured on all the clinical visits

KM-001 0.3%; KM-001 1%; Vehicle arm

Investigator's Global Assessment DIAGNOSTIC_TEST

patient's disease evaluations will be evaluated on all the clinical visits

Also known as: score

KM-001 0.3%; KM-001 1%; Vehicle arm

Itch Assessment via PP-NRSj DIAGNOSTIC_TEST

patient's disease evaluations will be evaluated on all the clinical visits

Also known as: score

KM-001 0.3%; KM-001 1%; Vehicle arm

E-diary data OTHER

The patient will record IMP adminidsration and AE events in a diary every day throughout the all study period

KM-001 0.3%; KM-001 1%; Vehicle arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Read, understood, and signed an ICF before any investigational procedure(s) are performed.
• Male or female and aged ≥18 to 75 years at the time of screening.
• Chronic moderate to severe pruritus defined as:
• Itching that has been present for 6 weeks or more prior to the screening AND
• At the screening visit (Visit 1) and enrollment visit (Visit 2): peak pruritus-numerical rating scale (PP-NRS)24h is ≥7.
• Clinical diagnosis of LSC for at least 8 weeks prior to screening:
• LSC lesions defined as dry, scaly, thickened plaques of skin (lichenification) caused by repeated rubbing or scratching, on upper limbs, trunk, and/or lower limbs.
• To have no more than 3 lesions, total size not exceeding 5% of BSA from which one (target lesion) will be selected for treatment (minimum area of lesion selected for treatment: 0.5% BSA).
• Female patients of childbearing potential1 must use a highly effective birth control method(failure rate ˂1% per year when used consistently and correctly) (17) throughout the study and for at least 4 weeks after last application of IMP.
• In addition to the hormonal contraception, female patients must agree to use a supplemental barrier method during intercourse with a male partner (i.e., male condom) throughout the study and for at least 4 weeks after last application of IMP.
• Female patients must be having regular menstrual periods (interval of 21-35 days, duration of 2-7 days for several months) at the baseline visit (as reported by the patient); exception: patients using hormonal contraceptives that preclude regular menstrual periods, menopausal or hysterectomized patients. A male patient with a pregnant or non-pregnant female partner of childbearing potentialmust use adequate contraceptive methods (adequate contraceptive measures as required by local regulation or practice; as a minimum, the male patient must agree to use condom during treatment and until the end of relevant systemic exposure in the male subject (7 days post-treatment).
• Male patients must refrain from sperm donation throughout the study and for 7 days after the last study drug administration.
• \. Female patients of non-childbearing potential must meet one of the following criteria:
• Absence of menstrual bleeding for 1 year prior to screening without any other medical reason.
• Documented hysterectomy or bilateral oophorectomy at least 3 months before the study.

You may not qualify if:

• Known hypersensitivity or any suspected cross-allergy to the active pharmaceutical ingredient (API) and/or excipients.
• Chronic pruritus resulting from another active condition other than LSC such as, but not limited to, psoriasis, atopic dermatitis, lichen planus contact dermatitis, folliculitis, habitual picking, bullous autoimmune disease, neuropathy.
• Genital, anal or scalp LSC.
• History of or current confounding skin condition (psoriasis, cutaneous T-cell lymphoma \[mycosis fungoides or Sezary syndrome\], chronic actinic dermatitis with \[present or previous\] skin cancer on the site of LSC, bullous disorders, dermatitis herpetiformis).
• Cutaneous infection within 1 week before the screening visit or any infection requiring treatment with oral, parenteral antibiotics, antivirals, antiparasitics or antifungals or any topical within 1 week before the screening visit. Patients may be rescreened once the infection has resolved.
• Positive hepatitis B surface antigen \[HBsAg\], hepatitis B core antibody \[HBcAb\], hepatitis C antibody, or human immunodeficiency virus antibody serology results at the screening visit.
• Patients with active atopic dermatitis.
• Neuropathic and psychogenic pruritus, such as, but not limited to, notalgia paresthetica, brachioradial pruritus, small fiber neuropathy, skin picking syndrome, or delusional parasitosis.
• Patients with the following medical conditions:
• High blood pressure (BP), defined as resting systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg (according to 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice \[18\]).
• Patients with poorly controlled and/or complicated (retinopathy/nephropathy/neuropathy) diabetes glycosylated hemoglobin (HbA1c) of \>7%, fasting serum glucose \>130 mg/dl.
• Patients with history of angina pectoris and/or myocardial infarction.
• Systemic autoimmune conditions (including, but NOT limited to: systemic lupus erythematosus, rheumatoid arthritis etc.).
• Small fiber neuropathy.
• Any other condition that could, in the investigator's opinion, affect patient safety, his ability to participate in the study or ability of the investigator to assess the skin.

Sponsors & Collaborators

• Kamari Pharma Ltd: lead
• Bioskin GmbH: collaborator

Study Sites (2)

Fachklinik Bad Bentheim - Dermatologische Studienambulanz

Bensheim, 48455, Germany

Location

Rothhaar Studien GmbH

Berlin, 10783, Germany

Location

MeSH Terms

Conditions

Neurodermatitis

Interventions

Hematologic Tests; Urinalysis; Electrocardiography; Pregnancy Tests; Restraint, Physical

Condition Hierarchy (Ancestors)

Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Clinical Chemistry Tests; Diagnostic Techniques, Urological; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Electrodiagnosis; Diagnostic Techniques, Obstetrical and Gynecological; Behavior Control; Therapeutics; Immobilization

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The study will be performed double-blind. Double-blind means that neither the patient nor the investigational staff (investigator, study nurse, evaluators, etc.) will know which IMP a patient is receiving. This is to ensure that the evaluations are carried out without bias. The IMPs will be blinded by the manufacturer via the labelling procedure. IMPs will be identical in appearance and will be packaged identically so that treatment blind is maintained.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Topical application of approximately 1 g cream per defined treatment area (2% body surface area \[BSA\] including target lesion \[minimum 0.5% to maximum 2% BSA\]) twice daily during a 4-week treatment period (on Days 0 to 27 and one additional application in the morning of Day 28, i.e., 57 treatments)

Study Record Dates

• First Submitted: June 29, 2022
• First Posted: July 12, 2022
• Study Start: May 24, 2022
• Primary Completion: April 4, 2023
• Study Completion: April 4, 2023
• Last Updated: April 2, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)