| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Palmoplantar Pustulosis (PPP) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Palmoplantar Pustulosis (PPP) is a rare, recurrent, auto-immune, chronic inflammatory skin condition typically confined to the palms and soles. |
|
| 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 | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10050185 |
| E.1.2 | Term | Palmoplantar pustulosis |
| E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
|
| 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 |
| To evaluate the efficacy of RIST4721 in the treatment of subjects with moderate to severe PPP |
|
| E.2.2 | Secondary objectives of the trial |
• Key efficacy secondary endpoints (Please refer "Objectives and Endpoints" section 1.1 Synopsis of the Study Protocol for more details)
• Additional secondary efficacy endpoints (Please refer "Objectives and Endpoints" section 1.1 Synopsis of the Study Protocol for more details)
• To assess the safety of RIST4721 in this population (Please refer "Objectives and Endpoints" section 1.1 Synopsis of the Study Protocol for more details)
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Age and Sex
1. Male or female subject aged ≥18 years and < 75 years of age at the time of consent.
Type of Subject and Disease Characteristics
2. A physician-confirmed diagnosis of PPP (sterile, macroscopically visible pustules on the palms and/or soles) for at least 6 months prior to screening
based on documented clinical history (information obtained from medical chart or subject's physician, or directly from the subject), with presence of active pustulation and without evidence of infection on palms/or and soles at screening.
3. Moderate or severe PPP, as defined by PPPASI ≥12 and PPPGA ≥3 at screening and confirmed by central photographic assessment of PPGA at screening. Subjects must have an area involvement of at least 30% on 2 palmoplantar surfaces or at least 60% on one palmoplantar surface.
4. At randomization visit, all of the following must be met:
• PPPASI score must be ≥ 90% of the score at screening and PPPASI score of ≥12;
• PPPGA score must be ≥3 and ≥ the score at screening;
• PPPASI subscore of pustules/vesicles on at least one palm or sole ≥2.
5. Candidate for systemic therapy, defined as having PPP inadequately controlled by topical treatment, phototherapy, and/or previous systemic therapy. Eligible subjects shall demonstrate a lack of response or tolerability to local standard of care therapy for PPP or be contraindicated to such therapies.
6. Subject who wants to use an emollient should agree to use the same emollient, at the same frequency of application, for 7 days before Day 1/baseline and throughout the study.
Note: On the day of scheduled visits, subjects cannot apply emollient before their scheduled visit time. For more information on concomitant therapies, please refer to Section 6.7 of the Study Protocol.
7. At screening, the results of the ANC performed at the central laboratory must be ≥3.0 x 109 cells/L.
8. Subject has been previously vaccinated for SARS-CoV-2 or has chosen not to be vaccinated at the start of participation (screening) in the clinical study.
Contraception
Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Refer to Section 10.4 of the Study Protocol for more details.
9. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and negative urine pregnancy test at baseline, prior to randomization.
10. Female subject agrees to use a contraceptive method that is highly effective from consent until at least 5 days after the last study treatment administration
11. Male subject agrees to use condom and spermicide from consent until at least 5 days after the last study treatment administration.
Informed Consent
12. Evidence of a personally signed and dated ICF indicating that the subject has been informed of all pertinent aspects of the study prior to initiation of any subject-mandated procedures.
13. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Part B Inclusion Criteria
In addition, to be eligible for participation in Part B, subjects must meet
all the following at the extension enrollment visit:
Subject and Disease Characteristics
14. Must have completed Part A, been compliant with study procedures, and currently receiving study treatment (RIST4721 or placebo).
15. Subject does not have any new or existing condition that, in the opinion of the investigator, would make participation not be in the best
interest (e.g., compromise the well-being) of the subject or that could prevent, limit, or confound the protocol-specified assessments.
Informed Consent
16. Evidence of a personally signed and dated ICF indicating that the subject has been informed of all pertinent aspects of the study prior to
initiation of any subject-mandated procedures.
17. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. |
|
| E.4 | Principal exclusion criteria |
Exclusion Criteria (Part A only)
Medical Conditions and Diagnostic Assessments
1. Current diagnosis of superinfected hand dermatitis as a variant of contact or atopic hand dermatitis.
2. Any condition that, in the opinion of the investigator, would make participation not be in the best interest (e.g., compromise the well being) of the subject or that could prevent, limit, or confound the protocol-specified assessments including, but not limited (Please refer "Exclusion Criteria (Part A only)" section 5.2. of the Study Protocol for more details).
3. Evidence of latent tuberculosis (TB) infection (either purified protein derivative [PPD] ≥5 mm of induration or positive QuantiFERON-TB Gold test, irrespective of bacille Calmette-Guérin vaccination status).
Note: Subject will be evaluated for latent TB infection with a PPD test or a QuantiFERON-TB Gold test if one has not been performed in the last 6 months. Subjects with documented completed treatment for latent TB will be allowed to participate in the study without retesting.
4. Breastfeeding, pregnant, or planning to become pregnant during the study.
Prior Therapy and Prior/Concurrent Clinical Study Experience
5. Any topical medication (exception of emollients [see Section 6.7 of the Study Protocol]) to treat PPP, including corticosteroids, dapsone, retinoids, vitamin D analogs (such as calcipotriol), or tar withing 2 weeks prior to Day 1.
6. Any systemic treatment that affects PPP, including, but not limited to, corticosteroids, oral retinoids, immunosuppressive medication, methotrexate, cyclosporine, dapsone, colchicine, or apremilast within 4 weeks prior to Day 1. Note: Intranasal corticosteroids and inhaled corticosteroids for stable medical conditions are allowed if subject has been on a stable dose for at least 4 weeks prior to Day 1 and agrees to maintain the same dose for the duration of the study. Eye drops containing corticosteroids are allowed.
7. Any ultraviolet (UV)-B phototherapy (including tanning beds) or excimer laser within 4 weeks prior to Day 1.
8. PUVA treatment within 4 weeks prior to Day 1.
9. Use of any marketed or investigational biological agent within 12 weeks or 5 half-lives (whichever is longer) prior to screening.
10. Currently receiving a nonbiological investigational product or investigational device or has received one within 4 weeks prior to Day 1.
11. Received strong cytochrome P450 (CYP)3A inhibitors and/or CYP3A inducers within 4 weeks prior to Day 1. Examples of strong CYP3A
inhibitors include but not limited to: cobicistat, boceprevir, ritonavir, indinavir, telaprevir, nelfinavir, danoprevir, dasabuvir, elvitegravir,
lopinavir, ombitasvir, paritaprevir, saquinavir, tipranavir itraconazole, ketoconazole, posaconazole, voriconazole, troleandomycin, clarithromycin, idelalisib, conivaptan, nefazodone. Examples of strong CYP3A inducers include by not limited to: apalutamide,carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John’s wort).
12. Received RIST4721 in prior study.
Other Exclusion Criteria
13. Excessive sun exposure or has used tanning booths within 4 weeks prior to Day 1, or subject is planning a trip where excessive sun exposure is expected or is not willing to minimize natural and artificial sunlight exposure during the study. Use of sunscreen products and protective apparel are permitted when exposure cannot be avoided.
14. Consumption of any food or beverages containing cranberry, pomegranate, starfruit, grapefruit, pomelos, exotic citrus fruits, or Seville oranges (including marmalade and juices made from these fruits) within 7 days before baseline and unwillingness to avoid these during the study.
15. Known or suspected allergy to RIST4721 or any component of the study treatment.
16. Close affiliation with the investigator (e.g., a close relative), including any study staff of the sites, persons working at the contract research organization (CRO), or subject is an employee of Sponsor.
17. Institutionalized because of legal or regulatory order. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Proportion of subjects achieving a 50% reduction in PPPASI score at Week 12 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 12 weeks (Part A, randomized, double-blind, placebo-controlled) and 72 weeks (Part B, open-label extension [OLE]) |
|
| E.5.2 | Secondary end point(s) |
Key Secondary:
• Proportion of subjects achieving Palmoplantar Pustulosis Physician Global Assessment (PPPGA) of 0 or 1 at Week 12
• Proportion of subjects achieving 75% reduction in PPPASI score at Week 12
Additional secondary efficacy endpoints:
• Absolute change from baseline in PPPGA at Week 12
• Absolute change from baseline in PPPASI at Week 12
To assess the safety of RIST4721 in this population:
•Incidence of TEAEs and SAEs
• Change from Baseline in clinical laboratory parameters, electrocardiogram (ECG) parameters, and vital signs
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| 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 | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| United States |
| Poland |
| Czechia |
| Germany |
| Hungary |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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