Assessment of KM-001 - Safety, Tolerability, and Efficacy in Patients With PPPK1 or PC

NCT05956314 | Completed Phase 1 DMC

• 1 other identifier: KM001-B1B
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase 1b, open-label, single-center, prospective trial will be assessing the safety, tolerability, and efficacy of topical KM-001 1% in patients with PPPK1 or PC diseases. In this study 2 cohorts will be recruited:

• Screening (Day -14 to -0): any time during the visit. (or on Day 1 up to 30 minutes pre-dose if missed during Screening)
• Day 7 and at EoT (Cohort 1: Day 84; Cohort 2: Day 112) up to 30 minutes pre-dose, and at 1 h, 2 h, 3 h, 6 h (+15 min) post-dose
• Days 28, 42 for both Cohorts, and Day 84 for Cohort 2: 1 sample after the first dose, before the second dose, as late as possible in the visit.
• End of Study (EoS, Day 112 (Cohort 1) or Day 140 (cohort 2)), or at Early Termination (ET): at any time during the visit. The patient will complete a patient-reported diary, consisting of treatment compliance and self-assessments for efficacy. Follow up- 2 weeks after EoT by phone call, and 4 weeks after EoT in clinic visit.

Conditions

Punctate Palmoplantar Keratoderma Type 1; Pachyonychia Congenita

Outcome Measures

Primary Outcomes (18)

• Safety endpoint will be assessed through collection and analysis of adverse events.

  Incidence rate of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) grouped by body system up to the patient´s end of trial (Day 112 \[Visit 12\]) or early termination \[ET\] visit\]).

  Up to 112 days

• Safety endpoint-will be assessed by the % of change from normal range in the collection of Hematology- laboratory blood test profile.

  Safety will be assessed by the % of change from normal range in clinical Hematology blood test profile from baseline (Day 1) up to day 112. Data management team will assess and review the laboratory blood test results (Hematology). Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition. The following values will be assessed: WBC (K/µl) and platelet count (K/µl), neutrophils (absolute \[abs.\])(K/µl), lymphocytes (abs.)(K/µl), monocytes (abs.) (K/µl), eosinophiles (abs.)(K/µl) and basophiles (abs.) (K/µl) and reticulocyte count (K/µl).

  Up to 112 days

• Safety endpoint-will be assessed by the % of change from normal range in the collection of MCH result in laboratory blood test.

  Safety will be assessed by the % of change from normal range in MCH (pg) blood test result, from baseline (Day 1) up to day 112. Data management team will assess and review the MCH lab test results. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition.

  Up to 112 days

• Safety endpoint-will be assessed by the % of change from normal range in the collection of MCV result in laboratory blood test.

  Safety will be assessed by the % of change from normal range in MCV(fl) laboratory blood test result, from baseline (Day 1) up to day 112. Data management team will assess and review the MCV lab test results. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition.

  Up to 112 days

• Safety endpoint-will be assessed by the % of change from normal range in the collection of haematocrit result in laboratory blood test.

  Safety will be assessed by the % of change from normal range in haematocrit (%) laboratory blood test result, from baseline (Day 1) up to day 112. Data management team will assess and review the haematocrit lab test results. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition.

  Up to 112 days

• Safety endpoint-will be assessed by the % of change from normal range in the collection of hemoglobin result in laboratory blood test.

  Safety will be assessed by the % of change from normal range in hemoglobin (g/dL) laboratory blood test result, from baseline (Day 1) up to day 112. Data management team will assess and review the hemoglobin lab test results. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition.

  Up to 112 days

• Safety endpoint-will be assessed by the % of change from normal range in the collection of RBC result in laboratory blood test.

  Safety will be assessed by the % of change from normal range in RBC (M/µl) laboratory blood test result, from baseline (Day 1) up to day 112. Data management team will assess and review the RBC lab test results. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition.

  Up to 112 days

• Safety endpoint-will be assessed by the % of change from normal range in the collection of Sodium, potassium and chloride results in chemistry laboratory blood test.

  Safety will be assessed by the % of change from normal range in chemistry laboratory blood test profile, from baseline (Day 1) up to day 112. Data management team will assess and review the chemistry lab test results. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition. The following values will be assessed: Sodium (mmol/L), potassium (mmol/L) and chloride (mmol/L).

  Up to 112 days

• Safety endpoint-will be assessed by the % of change from normal range in the collection of: Glucose fasting , BUN/Ur, creatinine, bilirubin total and direct, calcium, uric acid, and bilirubin result, in chemistry laboratory blood test.

  Safety will be assessed by the % of change from normal range in chemistry laboratory blood test profile, from baseline (Day 1) up to day 112. Data management team will assess and review the chemistry lab test results. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition. The following values will be assessed: Glucose fasting (mg/dL), BUN/Ur (mg/dL), creatinine (mg/dL), bilirubin total (mg/dL) and direct (mg/dL), calcium (mg/dL), uric acid (mg/dL), and bilirubin (mg/dL).

  Up to 112 days

• Safety endpoint-will be assessed by the % of change from normal range in the collection of Alkaline phosphatase, AST, ALT and GGT result in chemistry- laboratory blood test.

  Safety will be assessed by the % of change from normal range in chemistry laboratory blood test profile, from baseline (Day 1) up to day 112. Data management team will assess and review the chemistry lab test results. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition. The following values will be assessed: Alkaline phosphatase (U/L), AST (U/L), ALT (U/L) and GGT (U/L).

  Up to 112 days

• Safety endpoint-will be assessed by the % of change from normal range in the collection of Albumin and total protein result in chemistry- laboratory blood test.

  Safety will be assessed by the % of change from normal range in chemistry blood test profile, from baseline (Day 1) up to day 112. Data management team will assess and review the chemistry lab test results. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition. The following values will be assessed: Albumin (g/dL) and total protein (g/dL).

  Up to 112 days

• Safety endpoint-will be assessed by the % of change from normal range in the collection of Serology -in laboratory blood test profile.

  Safety will be assessed by the % of change from normal range in serology clinical blood test profile, from baseline (Day 1) up to Day 112. Data management team will assess and review the serology lab test results. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition. The following values will be assessed: HBsAg (positive/negative), HBcAb (positive/negative), hepatitis C antibody (positive/negative), or HIV antibody (positive/negative).

  Up to 112 days

• Safety endpoint-will be assessed by the % of change from normal range in the collection of urine laboratory profile.

  Safety will be assessed by the % of change in clinical urine laboratory profile from baseline (Day 1) up to Day 112. Data management team will assess and review the urine lab test results. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition. the following values will be assessed: Glucose (mg/dl), protein (mg/ml),urobilinogen (mg/ml) and ketones (mg/ml).

  Up to 112 days

• Safety endpoint-will be assessed by the % of change from normal range in the collection of Specific gravity , pH, blood and nitrites result in urine laboratory profile.

  Safety will be assessed by the % of change in clinical urine laboratory profile from baseline (Day 1) up to Day 112. Data management team will assess and review the urine lab test results. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition. The following values will be assessed: Specific gravity , pH, blood and nitrites.

  Up to 112 days

• Safety endpoint-Mean change in body temperature measurement from baseline.

  Mean changes in body temperature from baseline (Day 1) up to Day 112.

  Up to 112 days

• Safety endpoint-Mean change in pulse measurement from baseline.

  Mean changes in pulse (unites: beats per minute) measurements from baseline (Day 1)up to Day 112.

  Up to 112 days

• Safety endpoint- Mean change in blood pressure measurement from baseline.

  Mean changes in blood pressure (systolic and diastolic blood pressure \[unites: mm Hg\]) measurements from baseline (Day 1) up to Day 112.

  Up to 112 days

• Safety endpoint-ECG

  Mean changes in ECG parameters from baseline (Day 1) up to Day 112. the following ECG parameters will be recorded: heart rate (HR), PR, QT, and QTC interval and QRS complex.

  Up to 112 days

Secondary Outcomes (3)

• Efficacy end point - will be assessed by Clinical global impression of severity (CGI-S) questionaries

  Up to 84 days

• Efficacy end point - will be assessed by Patient global impression of change (PGI-S) questionaries

  Up to 84 days

• Efficacy end point - will be assessed by Patient global impression of change (PGI-C) questionaries

  Up to 84 days

Other Outcomes (5)

• Exploratory end point- will be assessed by characterize the time to reach Maximum plasma concentration (tmax) of KM-001

  Up to 112 days

• Exploratory end point- will be assessed by characterize the Area under the plasma concentration versus time curve (AUC) of KM-001

  Up to 112 days

• Exploratory end point -will be assess the efficacy of KM-001 1% in pain reduction resulted by Visual analogue scale (VAS) questionnaire.

  Up to 84 days

Study Arms (2)

KM-001 cream 1% 12 weeks treatment.

EXPERIMENTAL

KM-001 1% cream will be applied to the affected area, twice daily for 12 consecutive weeks. KM-001 will be supplied in glass jars (30 g) and will be provided to patients with spatulas and polyethylene gloves.

Drug: KM-001 cream 1% 12 weeks treatment.; Diagnostic Test: Physical Examination; Diagnostic Test: Vital Signs; Diagnostic Test: Serum chemistry; Diagnostic Test: Hematology; Diagnostic Test: Serology; Diagnostic Test: Urinalysis; Diagnostic Test: ECG test; Diagnostic Test: Pharmacokinetics Assessments; Diagnostic Test: Clinical global impression of severity (CGI-S); Diagnostic Test: Visual Analogue Scale (VAS) pain scale; Diagnostic Test: Peak pruritus-numerical rating scale (PP-NRS); Diagnostic Test: Patient global impression of change (PGI-C) scoring; Diagnostic Test: Patient global impression of severity (PGI-S) scoring; Diagnostic Test: Lesion photography

KM-001 cream 1% 16 weeks treatment.

EXPERIMENTAL

KM-001 1% cream will be applied to the affected area, twice daily for 16 consecutive weeks. KM-001 will be supplied in glass jars (30 g) and will be provided to patients with spatulas and polyethylene gloves.

Diagnostic Test: Physical Examination; Diagnostic Test: Vital Signs; Diagnostic Test: Serum chemistry; Diagnostic Test: Hematology; Diagnostic Test: Serology; Diagnostic Test: Urinalysis; Diagnostic Test: ECG test; Diagnostic Test: Pharmacokinetics Assessments; Diagnostic Test: Clinical global impression of severity (CGI-S); Diagnostic Test: Visual Analogue Scale (VAS) pain scale; Diagnostic Test: Peak pruritus-numerical rating scale (PP-NRS); Diagnostic Test: Patient global impression of change (PGI-C) scoring; Diagnostic Test: Patient global impression of severity (PGI-S) scoring; Diagnostic Test: Lesion photography; Drug: KM-001 cream 1% 16 weeks treatment.

Interventions

KM-001 cream 1% 12 weeks treatment. DRUG

KM-001 1% 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 84 days. IMP will be applied on the plantar surfaces.

Also known as: Experimental drug administration-cohort 1

KM-001 cream 1% 12 weeks treatment.

Physical Examination DIAGNOSTIC_TEST

A complete physical examination will be performed as follows at screening and baseline, abbreviated after that (i.e., on Days 7, 28, 42, 63, 84, 112, 140, and at ET visit - where applicable, per cohort): * The complete physical examination will cover a careful assessment of all body systems, including the head, eyes, ears, nose, and throat and the respiratory, cardiovascular, gastrointestinal (GI), musculoskeletal, neurological, dermatological, hematologic/lymphatic, and endocrine systems. Particular attention will be placed on the areas affected by the disease. * Symptom-directed physical examinations will be performed at all other trial visits. * Height and weight measurement will be performed at screening only. An abbreviated examination including a comprehensive skin examination.

KM-001 cream 1% 12 weeks treatment.; KM-001 cream 1% 16 weeks treatment.

Vital Signs DIAGNOSTIC_TEST

Vital sign measurements (oral body temperature, pulse, and resting systolic and diastolic blood pressure) will be measured at screening, on Days 1, 7, 28, 42, 63, 84, 112, 140, and at ET visit - where applicable, per cohort. Vital signs will be measured in supine position after at least 5 minutes of rest.

KM-001 cream 1% 12 weeks treatment.; KM-001 cream 1% 16 weeks treatment.

Serum chemistry DIAGNOSTIC_TEST

Approx. 5 mL whole blood will be collected after an ≥8 h fast for serum biochemistry assessments during screening, and on Days 1 (baseline), 7, 84 112, 140 or at an ET visit - where applicable, per cohort. Serum chemistry will include assessments of total and direct bilirubin, ALT, AST, gamma-glutamyl transferase (GGT), alkaline phosphatase, glucose (fasting), sodium, potassium, blood urea nitrogen (BUN/Urea), creatinine, chloride, calcium, uric acid, albumin, and total protein.

KM-001 cream 1% 12 weeks treatment.; KM-001 cream 1% 16 weeks treatment.

Hematology DIAGNOSTIC_TEST

Approx. 5 mL whole blood will be collected for complete blood count (CBC) during screening, and on Days 1 (baseline), 7, 84, 112, 140 or at an ET visit - where applicable, per cohort. The CBC assessments will include red blood cells (RBC), haemoglobin, haematocrit, reticulocyte count, platelet count, mean corpuscular haemoglobin (MCH), mean platelet volume (MCV), white blood cells (WBC), neutrophils (absolute \[abs.\]), lymphocytes (abs.), monocytes (abs.), eosinophils (abs.), and basophils (abs.).

KM-001 cream 1% 12 weeks treatment.; KM-001 cream 1% 16 weeks treatment.

Serology DIAGNOSTIC_TEST

Approx. 5 mL whole blood will be collected for serology assessments during screening. Serology will include HbsAg, HbcAb, hepatitis C antibody, and HIV antibody.

KM-001 cream 1% 12 weeks treatment.; KM-001 cream 1% 16 weeks treatment.

Urinalysis DIAGNOSTIC_TEST

General urinalysis will be performed, by dipstick, during screening, and on Days 1 (baseline), 7, and 84, 112, and 140, or at an ET visit - where applicable, per cohort. At least 7 to 10 mL of urine will be collected. Urinalysis will include pH, specific gravity, blood, nitrites, glucose, ketones, protein, bilirubin, urobilinogen, and leukocytes. A microscopic examination of the urine will be performed only if clinically indicated.

KM-001 cream 1% 12 weeks treatment.; KM-001 cream 1% 16 weeks treatment.

ECG test DIAGNOSTIC_TEST

A 12-lead, resting, ECG will be taken for each patient at screening, on Days 1 (baseline), 84, 112, and at day 140 (for Cohort 2), or at an ET visit - Where applicable. The measurement will be taken after the patient has been supine for at least 5 min. At minimum, the following ECG parameters will be recorded: heart rate (HR), PR, QT, and QTc interval and QRS complex. The report will be printed out and signed by the investigator, who will record in the eCRF whether it is normal, abnormal but not clinically significant, or abnormal AND clinically significant. In the latter case the eligibility of the patients will be reviewed.

KM-001 cream 1% 12 weeks treatment.; KM-001 cream 1% 16 weeks treatment.

Pharmacokinetics Assessments DIAGNOSTIC_TEST

Blood samples for PK will be collected during screening (Days -14 to 0) at any time during the visit, or on Day 1 (up to 30 minutes prior to the first dose, if not performed during Screening) and on Day 7 and at End of Treatment (EoT, Cohort 1: Day 84; Cohort 2: Day 112) up to 30 minutes pre-dose and at 1 h, 2 h, 3 h, 6 h (+15 min) post-dose, on Days 28, 42, and 84 (for Cohort 2): 1 sample after the first dose, before the second dose, as late as possible in the visit, at End of Study (EoS, Cohort 1: Day 112; Cohort 2: Day 140), or at an ET visit: at any time during the visit. * Altogether up to 15 samples, and approx. 30 mL of blood will be drawn for PK at screening or Day 1 and on Days 7, 28, 42, 84, EoT (84/112), and EoS (112/140), or at an ET visit, if applicable. * Overall, up to a total of 85 mL of blood will be drawn during the trial for blood and PK assessments per patient in Cohort 1, and 95 mL of blood per patient in Cohort 2.

KM-001 cream 1% 12 weeks treatment.; KM-001 cream 1% 16 weeks treatment.

Clinical global impression of severity (CGI-S) DIAGNOSTIC_TEST

Lesions severity will be assessed using the CGI-S scale, which is a 5-point scale (from 0= "none" to 4= "very severe") modified from Busner et al. 2007 (30) by the investigator during screening and on Days 1 (baseline, prior to first dosing), 7, 28, 42, 63, 84, 112, 140, and at ET visit - where applicable, per cohort). The clinician scoring takes into account all available information, including a knowledge of the patient's history, psychosocial circumstances, symptoms (pain), behaviour, and the impact of the symptoms on the patient's ability to function (ability to walk). investigators will complete the CGI-S at various timepoints based on the question. "Please choose the response that best describes your assessment of the disease severity, based upon the totality of information available to you"

KM-001 cream 1% 12 weeks treatment.; KM-001 cream 1% 16 weeks treatment.

Visual Analogue Scale (VAS) pain scale DIAGNOSTIC_TEST

The patient will enter the PPPK- or PC-related pain score (not any pain) using a VAS pain scale in the patient-reported diary, on a weekly basis starting on Day 1 through ET visit, prior to the second administration of the IMP (evening dose) at the same time every time (±1 hour) except for Day 1 (Visit 2, in-clinic visit), where the assessment will be performed pre-dose during the visit. The score will be collected on every in-clinic visit during the treatment and follow up periods (Days 1, 7, 28, 42, 63, 84, 112, 140, and at an ET visit - where applicable, per cohort). The following parameter will be evaluated on a VAS from 0 (no pain) to 100 (severe intolerable pain) based on the question: "How was your worst pain intensity in the past 24 hours?"

KM-001 cream 1% 12 weeks treatment.; KM-001 cream 1% 16 weeks treatment.

Peak pruritus-numerical rating scale (PP-NRS) DIAGNOSTIC_TEST

The peak pruritus severity will be assessed using the PP-NRS, an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). The PP-NRS will be entered by the patients on a weekly basis starting on Day 1 through ET visit, preferably after the evening dose, at the same time every time (±1 hour) except for Day 1 (Visit 2, in-clinic visit), where the assessment will be performed pre-dose during the visit. The scores will be collected on every in-clinic visit during the treatment and follow up periods (Days 1, 7, 28, 42, 63, 84, 112, and 140, or at an ET visit - where applicable, per cohort). The PP-NRS was designed to measure peak pruritus, or "worst" itch, over the previous 24 hours based on the following question: "On scale from 0 (no itch) to 10 (worst imaginable itch) how was your worst itch in the past 24 hours?"

KM-001 cream 1% 12 weeks treatment.; KM-001 cream 1% 16 weeks treatment.

Patient global impression of change (PGI-C) scoring DIAGNOSTIC_TEST

The PGI will be evaluated on Days 1, 7, 28, 42, 63, 84, 112, and 140, or at an ET visit - where applicable, per cohort. The PGI-C will be evaluated using a 7-point scale from 1 (very much improved) to 7 (very much worse) as follows: Since the start of the trial, my overall status has: from, 1= "very much improved" to 7= "very much worse"

KM-001 cream 1% 12 weeks treatment.; KM-001 cream 1% 16 weeks treatment.

Patient global impression of severity (PGI-S) scoring DIAGNOSTIC_TEST

The PGI will be evaluated on Days 1, 7, 28, 42, 63, 84, 112, and 140, or at an ET visit - where applicable, per cohort. The PGI-S will be evaluated using a 5-point scale from 1 (none) to 5 (very severe) as follows: Please rate the severity of your disease right now, from 1= "none" to 5= "very severe"

KM-001 cream 1% 12 weeks treatment.; KM-001 cream 1% 16 weeks treatment.

Lesion photography DIAGNOSTIC_TEST

High quality photographic documentation of the treated lesions will be performed during Screening and on Days 1, 7, 42, 63, 84, 112, and 140, or at an ET visit before treatment - where applicable, per cohort. The photographs will be taken under standardised conditions, using imitoMeasure (Ⓒ imito AG 2016-2022).

KM-001 cream 1% 12 weeks treatment.; KM-001 cream 1% 16 weeks treatment.

KM-001 cream 1% 16 weeks treatment. DRUG

KM-001 1% 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 112 days. IMP will be applied on the plantar surfaces.

Also known as: Experimental drug administration-cohort 2

KM-001 cream 1% 16 weeks treatment.

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 informed consent form (ICF) before any investigational procedure(s) are performed.
• Male and female and aged 18 - 75 years (inclusive) at the time of screening.
• Clinical diagnosis of:
• Punctate palmoplantar keratoderma type I disease with confirmed heterozygous mutation in AAGAB gene.
• PC with confirmed heterozygous mutation in either KRT16, KRT17, KRT6A, KRT6B or KRT6C mutations.
• The target treatment region is 0.5% to 4% BSA including target lesion.
• CGI-S score (as assessed by the CI at the screening visit) of ≥2.
• Female patients of childbearing potential1 must use a highly effective birth control method2 (failure rate ˂1% per year when used consistently and correctly) (28) throughout the trial 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 trial and for at least 4 weeks after last application of IMP.
• Female patients must be having regular menstrual periods (interval of 21 to 35 days, duration of 2 to 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 hysterectomised patients.
• A male patient with a pregnant or non-pregnant female partner of childbearing potential1 must 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 patient (7 days post-treatment).
• A female patient is considered of childbearing potential, i.e., fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for at least 12 months without an alternative medical cause prior to screening (28).
• Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) or progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) 28 days prior to screening, bilateral tubal occlusion, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), vasectomised/permanently sterile by bilateral orchidectomy partner (given that the partner is the sole sexual partner and has received medical assessment of the surgical success), or sexual abstinence (refraining from heterosexual intercourse during the entire trial/treatment period of risk associated with the IMPs) (28). This period of contraception should be extended for at least 4 weeks after last application of IMP.
• \. Female patients must refrain from donating eggs throughout the trial and for 4 weeks after the last IMP administration.
• Male patients must refrain from sperm donation throughout the trial and for 7 days after the last IMP administration.

You may not qualify if:

• History of drug or alcohol abuse in the past 2 years.
• Regular alcohol consumption in males \>21 units per week and females \>14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine).
• Positive hepatitis B surface antigen \[HbsAg\], hepatitis B core antibody \[HbcAb\], hepatitis C antibody, or human immunodeficiency virus (HIV) antibody serology results at the screening visit.
• Known hypersensitivity or any suspected cross-allergy to the API and/or excipients.
• Any medical or active psychological condition or any clinically relevant laboratory abnormalities, such as, but not limited, to elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (\>3 × upper limit of normal \[ULN\]) in combination with elevated bilirubin (\>2 × ULN), at the screening/baseline visit.
• Planned or expected major surgical procedure during the clinical trial.
• Patient is unwilling to refrain from using prohibited medications during the clinical trial.
• Currently participating or participated in any other clinical trial of an IMP or device, within the past 4 months before the screening visit.
• Cutaneous infection or another underlying condition of the skin which may impact the assessments or trial participation.
• Cutaneous infection of the area to be treated with IMP within 2 weeks before the screening visit or any infection of treatment area requiring treatment with oral, parenteral antibiotics, antivirals, antiparasitics or antifungals or any topical within 2 weeks before the screening visit.
• Pregnant or breastfeeding patient.
• Failure to satisfy the investigator of fitness to participate for any other reason.
• Having received any of the prohibited treatments in Table 5 within the specified timeframe before the baseline visit.

Sponsors & Collaborators

• Kamari Pharma Ltd: lead

Study Sites (1)

Royal London Hospital-Clinical Research Facility-11D (11th Floor) Whitechapel, London, E1 1FR,

London, Whitechapel Rd, United Kingdom

Location

MeSH Terms

Conditions

Keratosis palmoplantaris papulosa; Pachyonychia Congenita

Interventions

Therapeutics; Physical Examination; Vital Signs; Hematologic Tests; Urinalysis; Pain Measurement

Condition Hierarchy (Ancestors)

Ectodermal Dysplasia; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Nail Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques and Procedures; Diagnosis; Clinical Laboratory Techniques; Investigative Techniques; Clinical Chemistry Tests; Diagnostic Techniques, Urological; Neurologic Examination

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: In this phase 1b, open label trial, 2 arms will be treated twice daily with 1% topical KM-001 (2 feet): 1. Arm 1: up to 11 eligible patients. 2. Arm 2: up to 7 eligible patients. During active treatment, safety, tolerability, efficacy, and PK assessments will be performed. Four (4) weeks after the end of active treatment, patients will return to the clinic for additional safety, efficacy, and PK assessments. Safety, tolerability, and efficacy parameters will be assessed during in-clinic visits as follow: For both cohorts: Screening, Enrolment, Days 7, 28, 42, 63. Additionally: For arm 1: Day 84 \[end of treatment\], 112 \[End of Study\] For arm 2: day 84, 112 \[EoT\] and 140 EoS\] post first investigational medicinal product (IMP) administration. Safety and treatment compliance assessment will be done by phone calls on - Cohort 1: Days 14, 49, 70, and 98 (follow-up); Cohort 2: Days 14, 49, 70, 98, and 126 (follow-up).

Study Record Dates

• First Submitted: June 14, 2023
• First Posted: July 21, 2023
• Study Start: March 6, 2023
• Primary Completion: November 7, 2024
• Study Completion: November 7, 2024
• Last Updated: January 15, 2025

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)