E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037084 |
E.1.2 | Term | Prurigo nodularis |
E.1.2 | System Organ Class | 100000004858 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objectives of this study are to evaluate the efficacy and safety of VPD-737 5-mg tablets and the placebo taken orally once daily for 8 weeks for the treatment of prurigo nodularis (PN). |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males or females who are at least 18 years and no more than 80 years of age at Screening.
2. Must have PN (defined as the presence of pruritic nodules due to chronic pruritus,) of more than 6 weeks duration despite treatment with current therapies such as antihistamines or corticosteroids (“treatment resistant” PN).
3. Must have PN lesions on both arms, both legs, and/or the trunk (ie, the lesions must not be localized).
4. Must have a VAS pruritus score of 70 or greater within 72 hours of Baseline.
5. Males, non-fecund females (ie, surgically sterilized, if procedure was done 12 months before screening or subject is postmenopausal, without menses for 12 months before screening), or females of childbearing potential using an acceptable method of birth control for a period of 35 days before the first dosing, and all females must have a negative pregnancy test at the screening and baseline visits:
Note 1: Acceptable methods of birth control include any one of the following: abstinence, vasectomized sexual partner, hormonal methods (ie, birth-control pill, hormonal IUD, Depo-Provera, implants, patch, intravaginal device [NuvaRing]), intrauterine device (IUD [copper banded coils]), diaphragm, cervical cap, or condom with spermicidal jelly or foam. Subjects using oral contraceptives must also use a reliable backup method of birth control during the study and until the first menses after the last dose of study medication or for 14 days menses after the last dose of study medication.
6. Willing and able to understand and provide written informed consent.
7. Willing and able to comply with study requirements and restrictions including the discontinuation of all current therapies for pruritus.
8. Subjects must be in good health as determined by medical history, physical examination, and results of ECG and clinical laboratory tests (including urinalysis).
9. Agreeing to confidential use and storage of all data and use of all anonymized data for publication including scientific publication.
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E.4 | Principal exclusion criteria |
1Have chronic pruritus due conditions other than PN, such as the following conditions: Lichen simplex chronicus, Lichen amyloidosus, Localized pruritus (e.g., only one arm affected), Neuropathic and psychogenic pruritus (notalgia paresthetica, brachioradial pruritus, somatoform prurigo, dilusional parasitosis, depression associated prurigo), Active dermatoses needing immediate therapy such as atopic dermatitis (without PN) or bullous pemphigoid;
2Have a history of use (within the specified time periods) of the medications listed below. Prior to randomization, a subject who used any of these medications must undergo a washout period equal to the length of the interval specified below (eg, 5 days for antihistamines, 2 weeks for naltrexone, and 2 weeks for cyclosporine A).
- topical or systemic antihistamines, (used ≤5 days prior to the baseline visit) [loratindine, or cetirizine may act as rescue medication during treatment];
- topical calcineurin inhibitors, topical capsaicin, menthol, camphor, polidocanol, topical antibiotics, antiseptic baths and cleansing lotions (used ≤1 week prior to the baseline visit);
- topical steroids (used ≤2 weeks prior to the baseline visit);
- naltrexone, paroxetine, fluvoxamine, amitriptyline, gabapentin, pregabalin, or UV-therapy (prescribed for the pruritus treatment) (used ≤2 weeks prior to the baseline visit);
- systemic steroids (used ≤2 weeks prior to the baseline visit);
- cyclosporine A and other immunosuppressants (used ≤2 weeks prior to the baseline visit).
3Have any medical condition or disability that would interfere with the assessment of safety or efficacy in this trial or would compromise the ability of the subject to undergo study procedures or to give informed consent.
4Have any chronic or acute medical condition that, in the opinion of the investigator, might interfere with the study results or place the subject at undue risk.
5Have a history of sensitivity to any components of the study material.
6Are females of childbearing potential who are unwilling to use adequate contraception or who are breast feeding.
7Have chronic renal disease, ie, serum creatinine greater than 2.4 mg/dL.
8Have aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 2 times the upper limit of normal. Subjects with hepatitis B or C who have normal liver function may be enrolled.
9Have a current malignancy (such as Hodgkin’s lymphoma, B or T cell lymphoma, or myeloma) or blood cell dyscrasia (eg, polycythemia or myelofibrosis) that might lead to systemic chronic pruritus.
10Subjects with untreated hyperthyroidism.
11Have pruritus of psychiatric etiology (eg, delusions of parasitosis, obsessive compulsive disorder, or major depression) or neuropathic etiology (eg, due to shingles, spinal cord injury or with neurologic deficit).
12Have pruritus due to urticaria, drug allergy, or infection (such as pityriasis rosea or tinea or active human immunodeficiency virus [HIV]). Note: Subjects with HIV who have undetectable viral load, CD 4 counts >200 cells/cc, and stable retroviral therapy may enroll.
13Are on medications known to cause pruritus (ie, Erbitux®, opioids, cocaine, amphetamines, and angiotensin converting enzyme [ACE] inhibitors) and are suspected of having drug-induced pruritus.
14Have taken investigational medications within 30 days prior to Screening.
15Are currently participating in any other clinical study.
16Have a history (within the previous 2 weeks) of use of tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRIS), monoamine oxidase (MAO) inhibitors, opioids, immune-modulators (e.g. azathioprine, methotrexate, mycophenolate mofetil, cyclosporine A, antibodies), or neuroactive medications (e.g. pregabalin, gabapentin)[...].
17Have a history (within the previous 4 weeks) of use of sedatives or tranquilizers. Subjects must undergo an appropriate washout period from any sedatives or tranquilizers before enrolling in the study.
18Are currently treated with strong CYP3A4 inhibitors (e.g. conazole, ketoconazole, fluconazole, itraconazole, voroconazole etc. or erythromycin). The co-administration of moderate CYP3A4 inhibitors to VPD-737 may be allowed with investigator agreement and appropriate safety monitoring.
19Received ultraviolet B (UVB) or psoralen + ultraviolet A (PUVA) treatment within ≤2 weeks prior to Baseline.
20Within the past 12 months, have expressed suicidal ideation with some intent to act.
21Started or changed creams, or emollients including over-the-counter (OTC) preparations or bath oil treatment for relief of pruritus within 1 week prior to Screening.
22Have any social or medical condition (eg, alcoholism, drug dependency, psychotic state) that, in the investigator’s opinion, might interfere with the subject’s ability to comply with the requirements of the protocol.
23Are employees of the study site or of the Sponsor’s company.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints of this double-blind, randomized clinical trial are pairwise comparisons between treatments of the VAS score (average over a 24 hour period) and the safety and tolerability of VPD 737 5-mg tablets and the placebo taken orally once daily for 8 weeks for the treatment of prurigo nodularis (PN). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoints of this double-blind, randomized clinical trial are pairwise comparisons between treatments of the VAS score (average over a 24 hour period) and the safety and tolerability of VPD 737 5-mg tablets and the placebo taken orally once daily for 8 weeks for the treatment of prurigo nodularis (PN). |
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E.5.2 | Secondary end point(s) |
• Mean change from Baseline in VRS, VAS (worst), patient global assessment score, dynamic score, and NRS.
• Mean change from Baseline in Quality of Life questionnaire results (Dermatology Life Quality Index (DLQI)/ Pruritus specific Quality of Life (ItchyQoL)); The DLQI/ItchyQoL will be scored according to the Instrument developers rules
• Mean change from Baseline in the Patient Benefit Index, Version for Patients with Pruritus (PBI-P) questionnaire results;
• Mean change from Baseline in PN skin lesions as measured by the Prurigo Activity Score (PAS);
• Mean change from Baseline in the Investigator Global Assessment (IGA);
• Time course of changes in VRS, NRS and VAS scores;
• Percentage of patients in each group requiring rescue medication with loratadine or cetirizine.
Safety will assessed using adverse events, serious adverse events, premature discontinuations from study, electrocardiograms, vital signs, abbreviated physical exams, and blood and urine laboratory tests.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary endpoints are descriptive pairwise comparisons between the VPD and placebo |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 24 |