Study of the Efficacy and Safety of RPH-104 in Adult Subjects With Schnitzler Syndrome

Brief Title

Study of the Efficacy and Safety of RPH-104 in Adult Subjects With Schnitzler Syndrome

Official Title

A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase 2 Study of the Efficacy and Safety of RPH-104 in Adult Subjects With Schnitzler Syndrome

Brief Summary

      The primary goal of the study is to assess the efficacy and safety of RPH-104 in subjects
      with Schnitzler Syndrome using Schnitzler Disease Activity Score (SDAS), which includes the
      Physician's Global Assessment (PGA) and the local laboratory C-reactive protein (CRP) result
    

Detailed Description

      The study will include a screening period (up to 28 days), a double blind, placebo controlled
      treatment period (14 days), followed by an 8 week safety follow up period after the second
      dose of study drug.

      Subjects with an established diagnosis of Schnitzler Syndrome (SchS) will participate in a
      Screening period of up to 28 days after signing an informed consent form (ICF). Subjects will
      be advised to schedule the Day 0 visit with the study staff as soon as the symptoms of SchS
      flare occur during the Screening period.

      If the subject does not meet the inclusion/exclusion criteria at the site visit during the
      screening period, other screening visits are allowed within this period until the subject
      meets the study criteria.

      A total of 14 subjects will be randomly assigned to 1 of 2 treatment groups (in a 1:1 ratio)
      to receive a double blind, single subcutaneous (SC) injection of study drug (80 mg RPH-104 or
      matching placebo) on Day 0. On Day 14, subjects will receive a second dose of randomized
      treatment as well as an additional dose of 80 mg RPH-104 or placebo based on response to
      treatment, such that responders (SDAS = 0) will receive a dose of placebo, and non responders
      defined as no response (no change in SDAS) or partial responders (SDAS ≥ 1, and activity
      reduction by 1 or more points of SDAS compared to baseline) will receive an 80 mg RPH 104
      dose. (Schnitzler Disease Activity Score includes the PGA score and C-reactive protein (CRP)
      result: If the PGA and CRP grades are not of the same severity, the higher severity level of
      either PGA or CRP will be used to determine the SDAS)

      The study will be stopped after Data and Safety Monitoring Board (DSMB) review if:

        1. Death is reported in 2 subjects assigned to the RPH 104 treatment arm or after receiving
           RPH 104 on Day 14 (i.e., non responder to the Day 0 study drug dose).

        2. Two subjects assigned to the RPH 104 treatment arm or after receiving RPH 104 on Day 14
           (ie, non responder to the Day 0 study drug dose) report liver function test
           abnormalities which meet Hy's Law criteria (ie, increased ALT and/or AST 3 fold or
           greater from upper limit of normal (ULN) combined with jaundice or weakness or
           hypochondrial pain/severity or increased Total Bilirubin (TBil) level 2 fold or greater
           from ULN, [not explained by any other causative factors like virus]).

      The severity of SchS symptoms will be assessed daily from Day 0 through Day 28 using the PR
      SchS Scale, at clinic visits on Day 0, Day 14, and Day 28 using the Patient Global Impression
      of Severity (PGIS), at clinic visits on Day 14 and Day 28 using the Patient Global Impression
      of Change (PGIC), and at each clinic visit using the PGA, CRP, SAA, and SDAS. Subjects will
      be followed through Day 70 for safety (A Data Safety Monitoring Board (DSMB) will
      periodically review and evaluate the accumulated study data for subject safety).
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Proportion of subjects with complete response (Schnitzler Disease Activity Score (SDAS = 0)) to therapy on Day 14 in the RPH-104 group as compared to the placebo group

Secondary Outcome

 Change from baseline to Day 14 in subject-reported symptom severity of SchS: Patient-reported Severity of Schnitzler Syndrome Scale (PR-SchS Scale)

Condition

Schnitzler Syndrome

Intervention

80 mg RPH-104

Study Arms / Comparison Groups

 Placebo - placebo
Description:  Subject randomized to receive subcutaneous single injection of placebo on Day 0,and then, on Day 14 - second dose of randomized treatment + based on the positive response to treatment (SDAS = 0) one more dose of placebo

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

14

Start Date

May 1, 2020

Completion Date

January 1, 2021

Primary Completion Date

August 1, 2020

Eligibility Criteria

        Inclusion Criteria:

          -  1. Able to read, understand and willing to sign the ICF and abide with study
             procedures. The ICF must be signed and dated prior to performing any Screening
             assessment.

          -  2. Confirmed diagnosis of SchS based on diagnostic criteria adapted by Lipsker as an
             urticarial skin rash (chronic), monoclonal IgM component (ie, IgM < 10 g/L), or IgG
             (variant type), and at least of 2 of the following:

               -  Fever (intermittent)

               -  Arthralgia or arthritis

               -  Bone pain

               -  Lymphadenopathy

               -  Hepato and/or splenomegaly

               -  Elevated erythrocyte sedimentation rate (ESR) and/or leukocytosis

               -  Bone abnormalities (on radiological or histological investigation)

          -  3. Subjects with symptomatic SchS (as defined by SDAS with a score of 2 or more with a
             CRP [local laboratory] levels > 10 mg/L) on the day of randomization.

          -  4. Willing, committed, and able to return for all clinic visits and complete all study
             related procedures, including willingness to have SC injections administered by a
             qualified person.

          -  5. Males, female partners of sexually active male subjects, and women of childbearing
             potential (WOCBP) (defined as all female subjects with physiological potential to
             conceive) must agree to use highly effective contraceptive methods throughout the
             study starting from Screening (signing informed consent) through at least 8 weeks
             after the final dose of study drug.

        Highly effective contraceptive method is defined as follows:

          1. Complete abstinence: if it corresponds to the preferred and conventional lifestyle of
             the female subject. Periodic abstinence (eg, calendar, ovulation, symptothermal,
             postovulation method) and interrupted coitus are not considered acceptable
             contraceptive methods.

          2. Sterilization: surgical bilateral ovariectomy (with/without hysterectomy) or tubal
             ligation at least 6 weeks prior to the study therapy initiation. In case of
             ovariectomy only the female reproductive status should be verified by further hormonal
             test.

          3. Sterilization of male partner with documented absence of sperm in ejaculate post
             vasectomy for at least 6 months (vasectomized male partner should be the only partner
             of the participating female subject).

          4. Combination of 2 of the following methods (i + ii, i + iii, or ii + iii):

        i. Oral, injectable, or implanted hormonal contraceptives; in case of oral contraceptives
        the female subjects should administer the same product for at least 3 months prior to the
        study therapy.

        ii. Intrauterine device or contraceptive system.

        iii. Barrier methods: condom or occlusive cap (diaphragm or cervical cap/vaginal fornix
        cap) with spermicidal foam/gel/film/cream/vaginal suppository.

          -  6. WOCBP must have negative pregnancy tests at Screening (serum chorionic gonadotropin
             test), and all subsequent visits (urine).

        Exclusion Criteria:

          -  1. Hypersensitivity to the study drug (RPH 104) and/or its components/excipients
             and/or the products of the same chemical class.

          -  2. Concurrent/on going treatment with anakinra (Kineret) or recent treatment within 5
             days prior to Day 0.

          -  3. Concurrent/on going treatment with other biologics or recent treatment within 4
             weeks or 5 × t½ prior to Day 0, whichever is longer.

          -  4. Concurrent/on going treatment with immunosuppressive agents (eg, cyclosporine,
             methotrexate, dapsone, colchicine, or others) within 4 weeks or 5 × t½ prior to Day 0,
             whichever is longer.

          -  5. Concurrent/on going treatment with high doses of systemic steroids (> 0.2 mg/kg/day
             prednisolone equivalent). Intra articular, peri articular, intravenous, or
             intramuscular corticosteroid injections within 4 weeks prior to the Day 0 visit.

          -  6. Administration of live (attenuated) vaccine within 3 months prior to Day 0 and
             necessity of live vaccine administration for 3 months after Day 70.

          -  7.

               1. History of active tuberculosis (TB), evidence of active or latent M. tuberculosis
                  infection as defined by local guidelines/local medical practice at Screening.

               2. Positive QuantiFERON Gold Plus (TB) test at Screening.

               3. Chest X ray findings confirming pulmonary TB at Screening.

          -  8. Active bacterial, fungal, or viral infection(s) within 4 weeks prior to Day 0.

          -  9. A history of persistent chronic bacterial, fungal, or viral infection(s) requiring
             treatment with parenteral antibiotics, parenteral antivirals, or parenteral
             antifungals within 4 weeks prior to Day 0.

          -  10. Opportunistic infections and/or Kaposi's sarcoma at the time of Screening.

          -  11. Any other relevant concomitant diseases (infectious, cardiovascular, nervous,
             endocrine, urinary, gastrointestinal, hepatic disorders, coagulation disorders, and
             other autoimmune/autoinflammatory diseases, etc) or conditions which, according to the
             investigator's judgment, may affect the subject's participation or well being in the
             study and/or distort assessment of the study results.

          -  12. History of malignancies within 5 years prior to screening other than successfully
             treated non metastatic, basal, or squamous cell carcinoma of the skin and/or in situ
             cancer.

          -  13. Evidence of lymphoproliferative diseases (except SchS associated monoclonal
             gammopathy).

          -  14. Presence of any of the following laboratory abnormalities at screening visit:
             white blood cell count (WBC) < 3000/µL; platelet count < 75,000/µL; alanine
             aminotransferase (ALT) or aspartate aminotransferase (AST) > 3.0 × upper limit of
             normal (ULN), TBil > 2 × ULN unless due to Gilbert's syndrome.

          -  15. Severe renal failure: Cockcroft Gault creatinine clearance < 30 mL/min.

          -  16. Women who are either pregnant or lactating.

          -  17. Subjects for whom there is concern about compliance with the protocol procedures.

          -  18. Psychiatric disorders which, according to the investigator's judgment, may affect
             the subject participation in the study and his/her ability to follow the protocol
             procedures.

          -  19. History of organ transplantation or transplantation is anticipated during the
             study.

          -  20. Concomitant participation in other clinical studies at the start of Screening or
             administration of any unauthorized (investigational) products less than 4 weeks or 5 ×
             t½ periods (whichever is longer) before Day 0 (treatment initiation).
      

Gender

All

Ages

18 Years - 100 Years

Accepts Healthy Volunteers

No

Contacts

Yan Lavrovsky, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04213274

Organization ID

CL04018066


Responsible Party

Sponsor

Study Sponsor

R-Pharm Overseas, Inc.

Collaborators

 Worldwide Clinical Trials

Study Sponsor

Yan Lavrovsky, Study Director, R-Pharm Overseas, Inc.


Verification Date

March 2020