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

NCT04213274 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: CL04018066
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

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

Conditions

Schnitzler Syndrome; Urticarial Vasculitis With Monoclonal Immunoglobulin M Component, Schnitzler (Disorder)

Keywords

neutrophilic urticarial dermatosis; autoinflammatory syndrome; monoclonal gammopathy; neutrophilic dermatosis; interleukin-1; Schnitzler syndrome

Outcome Measures

Primary Outcomes (1)

• 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

  • Proportion of subjects with complete response (SDAS = 0) to therapy on Day 14 in the RPH 104 treated group as compared to the placebo group based on SDAS using the PGA and the local laboratory CRP result

  Day 14

Secondary Outcomes (5)

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

  Baseline and Day 14

• Proportion of subjects with normalized serum amyloid A (SAA) and C-reactive protein (CRP) at Days 14 and 28

  Day 14 and Day 28

• Change from baseline to Day 14 and Day 28 in CRP and SAA

  Baseline, Day 28 and Day 14

• Proportion of subjects with complete response (SDAS = 0) to therapy on Day 28 by treatment sequence based on SDAS using the Physician's Global Assessment (PGA) and the CRP result

  Baseline and Day 28

• Proportion of subjects with partial response by treatment sequence on Days 14 and 28

  Baseline, Day 14 and Day 28

Other Outcomes (20)

• Change from baseline to Day 28 in subject reported symptom severity of SchS using the PR SchS Scale

  Baseline, Day 14 and Day 28

• Change from baseline to Day 14 and Day 28 in the Short Form-36 Version 2 Health Survey®

  Baseline, Day 14 and Day 28

• Change from baseline to Day 14 and Day 28 in PGA total score

  Baseline, Day 14 and Day 28

Study Arms (4)

Placebo - placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Placebo - 80 mg RPH-104

OTHER

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 lack of response (no change in SDAS) or partial response to treatment (SDAS ≥ 1, and activity reduction by 1 or more points of SDAS compared to baseline) subcutaneous single injection of 80 mg RPH-104

Biological: 80 mg RPH-104; Drug: Placebo

80 mg RPH-104 - 80 mg RPH-104

EXPERIMENTAL

Subject randomized to receive subcutaneous single injection of 80 mg RPH-104 on Day 0,and then, on Day 14 - second dose of randomized treatment + based on the positive response to the treatment (SDAS = 0) one subcutaneous injection of placebo

Biological: 80 mg RPH-104; Drug: Placebo

80 mg RPH-104 - 160 mg RPH-104

EXPERIMENTAL

Subject randomized to receive subcutaneous single injection of 80 mg RPH-104 on Day 0,and then, on Day 14 - second dose of randomized treatment + based on the lack of response (no change in SDAS) or partial response to treatment (SDAS ≥ 1, and activity reduction by 1 or more points of SDAS compared to baseline) one more subcutaneous injection of 80 mg RPH-104

Biological: 80 mg RPH-104

Interventions

80 mg RPH-104 BIOLOGICAL

solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL glass vial

80 mg RPH-104 - 160 mg RPH-104; 80 mg RPH-104 - 80 mg RPH-104; Placebo - 80 mg RPH-104

Placebo DRUG

Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4 mL-glass vial

80 mg RPH-104 - 80 mg RPH-104; Placebo - 80 mg RPH-104; Placebo - placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.
• \. 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)
• \. 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.
• \. 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.
• \. 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:
• 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.
• 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.

You may not qualify if:

• \. Hypersensitivity to the study drug (RPH 104) and/or its components/excipients and/or the products of the same chemical class.
• \. Concurrent/on going treatment with anakinra (Kineret) or recent treatment within 5 days prior to Day 0.
• \. Concurrent/on going treatment with other biologics or recent treatment within 4 weeks or 5 × t½ prior to Day 0, whichever is longer.
• \. 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.
• \. 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.
• \. Administration of live (attenuated) vaccine within 3 months prior to Day 0 and necessity of live vaccine administration for 3 months after Day 70.
• History of active tuberculosis (TB), evidence of active or latent M. tuberculosis infection as defined by local guidelines/local medical practice at Screening.
• Positive QuantiFERON Gold Plus (TB) test at Screening.
• Chest X ray findings confirming pulmonary TB at Screening.
• \. Active bacterial, fungal, or viral infection(s) within 4 weeks prior to Day 0.
• \. 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.
• \. Opportunistic infections and/or Kaposi's sarcoma at the time of Screening.
• \. 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.
• \. 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.
• \. Evidence of lymphoproliferative diseases (except SchS associated monoclonal gammopathy).

Sponsors & Collaborators

• R-Pharm Overseas, Inc.: lead
• Worldwide Clinical Trials: collaborator

Study Sites (4)

National Jewish Health

Denver, Colorado, 80206, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239-3098, United States

Location

Penn State Health Hersey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

MeSH Terms

Conditions

Schnitzler Syndrome; Paraproteinemias

Condition Hierarchy (Ancestors)

Monoclonal Gammopathy of Undetermined Significance; Immunoproliferative Disorders; Immune System Diseases; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Yan Lavrovsky

  R-Pharm Overseas, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2019
• First Posted: December 30, 2019
• Study Start: May 1, 2023
• Primary Completion: August 1, 2023
• Study Completion: January 1, 2024
• Last Updated: November 15, 2024

Record last verified: 2024-11

Locations

US (4)