Efficacy and Safety Clinical Study of RPH-104 in Adult Onset Still's Disease (AOSD)

NCT05432960 | Withdrawn Phase 3

• 1 other identifier: CL04018093
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

Brief Summary

The primary objective of the study is to evaluate the efficacy of RPH-104 when administered at a dose of 160 mg on Day 0, Day 7, Day 21 and then once every 2 weeks (Q2W) subcutaneous (SC) in patients with Adult Onset Still's Disease (AOSD). Furthermore, the study is scheduled to investigate pharmacokinetic (PK) and pharmacodynamic (PD) parameters of RPH-104.

Conditions

Adult-Onset Still's Disease; AOSD

Keywords

RPH-104; subcutaneous

Outcome Measures

Primary Outcomes (1)

• Time (number of days) to exacerbation during 24 weeks after randomization while taking RPH-104 vs placebo in patients with AOSD

  The criteria for exacerbation are (more than 2 criteria or worsening of more than 2 previous criteria): * fever (body temperature ≥ 38.0 °C) due to AOSD during a week before the visit; * rash typical of AOSD; * clinical disease activity index (CDAI) \> 2.8 for subjects with inactive disease; \> 10 for subjects with low disease activity\*; * sore throat\*; * pericardial effusion ≥ 7 mm\*; * pleuritis\*; * chest pain \> 3 numeric rating scale (NRS)\*; * C-reactive protein (CRP) \> 5 mg/L\*; * aminotransferase (ALT, AST) level \> 3 x upper limits of normal (ULN)\*; * leukocyte count \> 10 x 10\^9/L with \> 80 % polymorphonuclear neutrophils\*; * ferritin level \> 3 x ULN\*; * Patient's Global Assessment (PtGA) worsening by 2 cm and more; * Physician's Global Assessment (PGA) worsening by 2 cm and more; * myalgia\*; * hepatomegaly\*; * splenomegaly\*; * lymphadenopathy\*. \* Increase/presence of noted signs due to other reason than AOSD should not be considered in the activity assessment for AOSD exacerbation.

  from randomization (visit 16, week 29) to exacerbation, up to week 53

Secondary Outcomes (7)

• Proportion of patients from RPH-104 group who developed AOSD exacerbation during 24 weeks after randomization vs placebo

  up to week 53

• Proportion of patients who developed AOSD exacerbation during the run-in period

  up to week 29

• Proportion of patients with fever resolution

  up to Day 14

• Proportion of patients with Simple disease activity index (SDAI) ≤ 3.3

  up to Day 203

• Proportion of patients with CDAI 3.3 - 11

  up to Day 203

Study Arms (2)

RPH-104

EXPERIMENTAL

The investigational product RPH-104 as SC injections at a dose of 160 mg on Day 0, Day 7, Day 21 and then once every 2 weeks (Q2W).

Biological: RPH-104

Placebo

PLACEBO COMPARATOR

placebo SC Q2W (equivalent to investigational product volume)

Drug: Placebo

Interventions

RPH-104 BIOLOGICAL

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

Also known as: goflikicept, Arcerix

RPH-104

Placebo DRUG

Normal Saline (0.9% Sodium Chloride solution)

Placebo

Eligibility Criteria

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

You may qualify if:

• Presence of voluntarily signed and dated Informed Consent Form to participate in this study.
• Definite diagnosis of Still's disease made on the basis of Yamaguchi diagnostic criteria (Yamaguchi M., 1992).
• A patient with AOSD (with inactive disease / low disease activity / exacerbation).
• In case of current GCs administration, their doses should be stable for at least 2 weeks prior to Day 0. Maximum acceptable dose calculated as 1 mg/kg/day is up to 60 mg/day.
• In case of on-going methotrexate (MTX) administration, the dose should be stable for at least 4 weeks prior to Day 0. Maximum acceptable dose is 30 mg/week. In case of withdrawal of previous MTX administration, it should be made at least 4 weeks before Day 0.
• Ability and willingness of the subject, according to the reasonable investigator's judgment, to attend the study site at all scheduled visits, undergo the study procedures and follow the protocol requirements including subcutaneous injections by qualified site personnel.
• Consent of female subjects with childbearing potential, defined as all females with physiological potential to conceive (except for those with absolute termination of menses to be determined retrospectively after 12 months of natural amenorrhea, i. e. amenorrhea with relevant clinical status, e. g. appropriate age) to use highly effective contraception throughout the study starting from the screening (signed Informed Consent Form) and for at least 8 weeks after discontinuation of the study product administration; and negative pregnancy test (serum test for chorionic gonadotropin).
• OR Consent of male subjects leading active sexual life to use highly efficient contraceptive measures throughout the study starting from the moment of signing the Informed Consent Form and for at least 8 weeks after the study product discontinuation.
• Highly effective contraceptive method is defined as follows:
• complete abstinence: if complies with patients' preferable and habitual way of life. Periodic abstinence (e. g. calendar, ovulation, symptothermal, post-ovulation methods) and interrupted intercourse are not acceptable contraception methods;
• surgical intervention for female sterilization: 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;
• surgical intervention for male sterilization (with a relevant documented lack of the sperm in the post-vasectomy ejaculate) at least 6 months prior to screening. For female subjects, a vasectomized sexual partner should be the only partner;
• combination of any two of the following methods (a+b or a+c or b+c):
• oral, injection 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;
• intrauterine device or contraceptive system;

You may not qualify if:

• Hypersensitivity to the investigational product (RPH-104) and/or its ingredients/excipients.
• Previous administration of:
• rilonacept - less than 6 weeks prior to Day 0 of the study;
• canakinumab - less than 12 weeks prior to Day 0 of the study;
• anakinra - less than 1 week prior to Day 0 of the study;
• tumor necrosis factor alpha (TNF-a) antagonists, Interleukin 6 (IL-6) inhibitors - less than 12 weeks prior to Day 0 of the study;
• Janus kinase inhibitors - less than 1 week prior to Day 0 of the study;
• immunosuppressants (azathioprine, cyclosporin, mycophenolate mofetil, tacrolimus, sirolimus, mercaptopurine, etc., except for methotrexate) - less than 24 weeks prior to Study Day 0;
• pulse therapy with GC (e. g., methylprednisolone 250-1000 mg/day intravenously or dexamethasone equivalent for 3 days) - less than 4 weeks (from the end of pulse therapy) to Study Day 0;
• any other biological product - less than 5 half-lives prior to Study Day 0.
• Administration of live (attenuated) vaccine less than 3 months prior to Visit 1 (study treatment period initiation) and/or necessity to use such vaccine within 3 months after the study therapy discontinuation. Live attenuated vaccines include viral vaccines against: measles, rubella, parotitis, varicella, rotavirus, influenza (as nasal spray), yellow fever, poliomyelitis (oral polio-vaccine), tuberculosis vaccine (BCG), typhoid (oral typhoid fever vaccine) and camp fever (epidemic typhoid vaccine). Immunocompetent family members should refuse to use oral polio-vaccine throughout the subject's participation in the study.
• Conditions or signs which, according to the investigator, suggest impaired (reduced) immune response and/or significantly increase the risk of immunomodulating therapy including (but not limited to):
• active bacterial, fungal, viral or protozoal infection at screening onset;
• opportunistic infections and/or Kaposi's sarcoma at the screening period onset;
• chronic bacterial, fungal or viral infection requiring systemic therapy with parenteral products at the main screening period onset;

Sponsors & Collaborators

• R-Pharm International, LLC: lead
• Exacte Labs LLC: collaborator
• Ministry of Health, Russian Federation: collaborator
• Scientific Center EFiS LLC: collaborator
• Data Management 365: collaborator

Study Sites (4)

Research Institute of Rheumatology. V.A. Nasonova

Moscow, 115522, Russia

Location

Clinic of Nephrology, Internal and Occupational Diseases. EAT. Tareeva, University Clinical Hospital No. 3

Moscow, 119991, Russia

Location

State Budgetary Institution of Healthcare Leningrad Regional Clinical Hospital, Department of Rheumatology

Saint Petersburg, 194291, Russia

Location

FGBU "National Medical Research Center named after V.A. Almazov", Ministry of Health of the Russian Federation, Department of Rheumatology

Saint Petersburg, 197341, Russia

Location

MeSH Terms

Conditions

Still's Disease, Adult-Onset

Condition Hierarchy (Ancestors)

Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Mikhail Samsonov

  Chief Medical Officer, R-Pharm

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2022
• First Posted: June 27, 2022
• Study Start: December 1, 2023
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: November 15, 2024

Record last verified: 2024-11

Locations

RU (4)