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

K

Kamari Pharma

Status and phase

Completed
Phase 1

Conditions

Lichen Simplex Chronicus

Treatments

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

Study type

Interventional

Funder types

NETWORK
Industry

Identifiers

NCT05454462
KM-001AB1

Details and patient eligibility

About

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).

Full description

This phase I study will be performed in patients with LSC instead of healthy subjects as in these patients, the significant histological changes (acanthosis and parakeratosis) result in heavily altered physiology and anatomy of the skin and any data including tolerability generated by administering the IMP on healthy skin can hardly be extrapolated to patients with LSC.

The setting can be compared with early studies in Psoriasis patients where it is established to include patients from the beginning. Based on preclinical experiments, no pharmacological relevant systemic absorption is expected.

PK sampling will be done for confirmation. Parallel group comparison is a common method and provides optimal conditions for examining efficacy. Comparisons to a vehicle is a common procedure. Randomization provides the most reliable and impartial method of determining differences between treatments as in this case active versus vehicle.

Double-blind conditions minimize any possible observer bias regarding treatment effects.

A vehicle control is included to evaluate the efficacy, safety, and tolerability of the cream without the active ingredient and to differentiate whether the drug substance or the drug product might cause any effects.

A duration of a 4-week treatment period is assumed to be appropriate to assess efficacy, safety, and tolerability based on preclinical data

Enrollment

55 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  1. Read, understood, and signed an ICF before any investigational procedure(s) are performed.

  2. Male or female and aged ≥18 to 75 years at the time of screening.

  3. Chronic moderate to severe pruritus defined as:

    1. Itching that has been present for 6 weeks or more prior to the screening AND
    2. At the screening visit (Visit 1) and enrollment visit (Visit 2): peak pruritus-numerical rating scale (PP-NRS)24h is ≥7.
  4. Clinical diagnosis of LSC for at least 8 weeks prior to screening:

    1. 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.
    2. 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).
  5. 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.

  1. Female patients of non-childbearing potential must meet one of the following criteria:

  2. Absence of menstrual bleeding for 1 year prior to screening without any other medical reason.

  3. Documented hysterectomy or bilateral oophorectomy at least 3 months before the study.

    1. Patient is willing and able to comply with all of the time commitments and procedural requirements of this CTP, including daily e-diary recordings by the patient using an electronic handheld device and an internet connection during the study.

Exclusion criteria

  1. Known hypersensitivity or any suspected cross-allergy to the active pharmaceutical ingredient (API) and/or excipients.

  2. 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.

  3. Genital, anal or scalp LSC.

  4. 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).

  5. 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.

  6. 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.

  7. Patients with active atopic dermatitis.

  8. Neuropathic and psychogenic pruritus, such as, but not limited to, notalgia paresthetica, brachioradial pruritus, small fiber neuropathy, skin picking syndrome, or delusional parasitosis.

  9. Patients with the following medical conditions:

    1. 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]).
    2. Patients with poorly controlled and/or complicated (retinopathy/nephropathy/neuropathy) diabetes glycosylated hemoglobin (HbA1c) of >7%, fasting serum glucose >130 mg/dl.
    3. Patients with history of angina pectoris and/or myocardial infarction.
    4. Systemic autoimmune conditions (including, but NOT limited to: systemic lupus erythematosus, rheumatoid arthritis etc.).
    5. Small fiber neuropathy.
    6. 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.
  10. Having received any of the prohiboted treatments in Table 1 within the specified timeframe before the baseline visit.

  11. Pregnant women (positive serum pregnancy test result at the screening and baseline visits), breastfeeding women, or women planning a pregnancy during the clinical trial.

  12. History of lymphoproliferative disease or history of malignancy of any organ system within the last 5 years, except for:

    1. Basal cell carcinoma, squamous cell carcinoma in situ (Bowen's disease), or carcinomas in situ of the cervix that had been treated and with no evidence of recurrence in the last 52 weeks before the baseline visit, or;
    2. Actinic keratoses that had been treated and with no evidence of recurrence in the last 8 weeks.
  13. Any known or suspected state of immunodeficiency due to primary or secondary immunodeficiency syndromes, organ transplants (except corneal transplant), previous opportunistic infection, or any other state of immunodeficiency as judged by the investigator.

  14. Any clinically relevant disorder or abnormal finding which could affect the safety of the patient throughout the study and/or impede the patient's ability to complete the study, as assessed by the investigator.

  15. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or bilirubin exceeding the upper limit of normal (ULN), or any other laboratory abnormalities considered clinically relevant by the investigator, at the screening/baseline visit.

  16. Any condition that may put the patient at significant risk according to the investigator's judgment.

  17. Any disorder which may interfere with study assessments (e.g., poor venous access or needle-phobia).

  18. Major surgical procedure planned or expected during the clinical trial.

  19. Patient is unwilling to refrain from using prohibited medications during the clinical trial.

  20. Currently participating or participated in any other study of a drug or device, within the past 2 months before the screening visit, or is in an exclusion period (if verifiable) from a previous study.

  21. Close affiliation with the investigator (e.g., a close relative) or persons working at bioskin GmbH or the study sites or patient is an employee of sponsor.

  22. Patient is institutionalized because of legal or regulatory order.

  23. Patients who have been administered any vaccine for COVID-19 within 30 days prior to first treatment.

  24. Tattoos and scars in the areas to be treated.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

55 participants in 3 patient groups, including a placebo group

KM-001 0.3%
Experimental group
Description:
KM-001 0.3% cream will be applied to the affected area twice daily for 4 consecutive weeks.
Treatment:
Diagnostic Test: Investigator's Global Assessment
Procedure: Physical Examination
Diagnostic Test: Blood PK sampling
Diagnostic Test: Urinalysis
Diagnostic Test: Chemistry
Diagnostic Test: Serelogy
Diagnostic Test: Pregnancy test
Diagnostic Test: Itch Assessment via PP-NRSj
Diagnostic Test: Hematology
Other: E-diary data
Procedure: Vital signa
Drug: IMP Application KM-001
Diagnostic Test: 12-Lead ECG
KM-001 1%
Experimental group
Description:
KM-001 0.3% cream will be applied to the affected area twice daily for 4 consecutive weeks.
Treatment:
Diagnostic Test: Investigator's Global Assessment
Procedure: Physical Examination
Diagnostic Test: Blood PK sampling
Diagnostic Test: Urinalysis
Diagnostic Test: Chemistry
Diagnostic Test: Serelogy
Diagnostic Test: Pregnancy test
Diagnostic Test: Itch Assessment via PP-NRSj
Diagnostic Test: Hematology
Other: E-diary data
Procedure: Vital signa
Drug: IMP Application KM-001
Diagnostic Test: 12-Lead ECG
Vehicle arm
Placebo Comparator group
Description:
Vehicle cream will be applied to the affected area twice daily for 4 consecutive weeks.
Treatment:
Diagnostic Test: Investigator's Global Assessment
Procedure: Physical Examination
Diagnostic Test: Blood PK sampling
Diagnostic Test: Urinalysis
Diagnostic Test: Chemistry
Diagnostic Test: Serelogy
Diagnostic Test: Pregnancy test
Diagnostic Test: Itch Assessment via PP-NRSj
Diagnostic Test: Hematology
Other: E-diary data
Procedure: Vital signa
Drug: IMP Application KM-001
Diagnostic Test: 12-Lead ECG

Trial contacts and locations

2

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Central trial contact

Alex Borzenko, B.sc; Liora Braiman-Wiksman, Ph.D.

Data sourced from clinicaltrials.gov

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