Clinical Efficacy and Safety of Leflunomide in Egyptian Patients With Active Rheumatoid Arthritis (CLEAR)

• ClinicalTrials.gov Identifier: NCT03599986
• Recruitment Status: Completed
• First Posted: July 26, 2018
• Results First Posted: June 30, 2020
• Last Update Posted: June 30, 2020
• Sponsor: Eva Pharma
• Collaborator: DataClin
• Information provided by (Responsible Party): Adel Mahmoud Elsayed, Eva Pharma

Tracking Information

• First Submitted Date: January 31, 2018
• First Posted Date: July 26, 2018
• Results First Submitted Date: May 5, 2020
• Results First Posted Date: June 30, 2020
• Last Update Posted Date: June 30, 2020
• Actual Study Start Date: June 16, 2017
• Actual Primary Completion Date: October 13, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 14, 2020)

• Number of Patients With Remission, Low, Moderate or High Disease Activity (in Terms of CDAI Scores) in Visits 1 and 6. [ Time Frame: 9 months ]
  Assessing the clinical efficacy of leflunomide as first-line therapy and as add-on therapy to other DMARDs, with or without steroids in Egyptian patients with active rheumatoid arthritis [in terms of the number of patients in remission (i.e. CDAI score 0.0 - 2.8), of low disease activity (i.e. CDAI score 2.9 - 10.0), of moderate disease activity (i.e. CDAI score 10.1 - 22.0) and of high disease activity (i.e. CDAI score 22.1 - 76.0) in visits 1 (at baseline) and 6 (at week 36)]. CDAI score: The sum of Tender joint score, Swollen joint score, Patient global score, and Patient global score. CDAI score interpretation: 0.0 - 2.8: Remission 2.9 - 10.0: Low Activity 10.1 - 22.0: Moderate Activity 22.1 - 76.0: High Activity
• Number of Patients With Different Disability Scores in Terms of the Mean Relative Change in Health Assessment Questionnaire - Disability Index Score on Visits 1 and 6. [ Time Frame: 9 months ]
  Assessing the clinical efficacy of leflunomide as first-line therapy and as add-on therapy to other DMARDs, with or without steroids in Egyptian patients with active rheumatoid arthritis [in terms of the number of patients with mild difficulties to moderate disability, moderate to severe disability and severe to very severe disability; according to the mean relative change in health assessment questionnaire - disability index score (HAQ-DI) at visits 1 (at baseline) and 6 (at week 36)]. A HAQ-DI score of 0.0 - 1 indicates mild difficulties to moderate disability, a HAQ-DI score of 1.1 - 2 indicates moderate to severe disability and a HAQ-DI score of 2.1 - 3 indicates severe to very severe disability. There are eight categories; first score within each category: Dressing and Grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Total score is the mean of the eight category scores. Higher scores indicate greater disability.

Original Primary Outcome Measures (submitted: July 24, 2018)

• The mean relative change in clinical disease activity index (CDAI) among patients with active rheumatoid arthritis treated with leflunomide throughout study duration. [ Time Frame: 9 months ]
  Assessing the clinical efficacy of leflunomide as first-line therapy and as add-on therapy to other DMARDs, with or without steroids in Egyptian patients with active rheumatoid arthritis (In terms of changes in CDAI score). CDAI score: The sum of Tender joint score, Swollen joint score, Patient global score, and Patient global score. CDAI score interpretation: 0.0 - 2.8: Remission 2.9 - 10.0: Low Activity 10.1 - 22.0: Moderate Activity 22.1 - 76.0: High Activity
• The mean relative change in health assessment questionnaire - disability index score (HAQ DI) among patients with active rheumatoid arthritis treated with leflunomide throughout study duration. [ Time Frame: 9 months ]
  Assessing the clinical efficacy of leflunomide as first-line therapy and as add-on therapy to other DMARDs, with or without steroids in Egyptian patients with active rheumatoid arthritis (In terms of changes in HAQ-DI score). There are eight categories; first score within each category:

  • Dressing and Grooming
  • Arising
  • Eating
  • Walking
  • Hygiene
  • Reach
  • Grip
  • Activities The score for the disability index is the mean of the eight category scores. The higher score indicates greater disability.

Current Secondary Outcome Measures (submitted: June 14, 2020)

Number of Adverse Events (AEs)/ Serious Adverse Events (SAEs) Experienced by Rheumatoid Arthritis Patients Receiving Leflunomide as First-line Therapy and as add-on Therapy to Other DMARD, With or Without Steroids and Their Relation to Study Medication. [ Time Frame: 9 months ]

Identifying the safety profile of leflunomide whether used as first-line therapy and/or as add-on therapy to other DMARDs with or without steroids in Egyptian patients with active rheumatoid arthritis.

Original Secondary Outcome Measures (submitted: July 24, 2018)

Number of adverse events (AEs)/ serious adverse events (SAEs) experienced by rheumatoid arthritis patients receiving leflunomide as first-line therapy and as add-on therapy to other DMARD, with or without steroids and their relation to study medication. [ Time Frame: 9 months ]

Identifying the safety profile of leflunomide whether used as first-line therapy and/or as add-on therapy to other DMARDs with or without steroids in Egyptian patients with active rheumatoid arthritis.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Clinical Efficacy and Safety of Leflunomide in Egyptian Patients With Active Rheumatoid Arthritis
• Official Title: A Phase IV, Multi-Centric, Prospective, Observational Study to Assess the Clinical Efficacy and Safety of Leflunomide in Egyptian Patients With Active Rheumatoid Arthritis
• Brief Summary: A Phase IV, Multi-Centric, Prospective, Observational Study to Assess the Clinical Efficacy and Safety of Leflunomide in Egyptian Patients with Active Rheumatoid Arthritis. (CLEAR)
• Detailed Description: CLEAR is a phase IV, multi-centric, prospective, observational study to assess the clinical efficacy and safety of Leflunomide as first-line therapy and as add-on therapy to other DMARDs (such as Methotrexate, Hydroxychloroquine, Sulfasalazine) with or without Steroids use in Egyptian patients with Active Rheumatoid Arthritis.
• Study Type: Observational
• Study Design: Observational Model: Other; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample

Study Population

Patients are between 18 and 60 years of age, with Active Rheumatoid Arthritis selected according to the ACR/EULAR classification criteria with score ≥ 6 points.

Patients are Leflunomide naïve or with previous Leflunomide administration (after at least 6-month wash out period from date of baseline visit).

Patients are with or without other DMARDs including Methotrexate, Sulfasalazine and/or Hydroxychloroquine with or without steroids use who experienced therapy resistance, inadequate response or intolerance.

• Condition: Active Rheumatoid Arthritis
• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 14, 2019): 398
• Original Estimated Enrollment (submitted: July 24, 2018): 400
• Actual Study Completion Date: October 13, 2018
• Actual Primary Completion Date: October 13, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Active Rheumatoid Arthritis patients selected according to the ACR/EULAR classification 2010 criteria with score ≥ 6 points.
2. Male or female patients aged 18-60 years old.
3. Leflunomide naïve patients or patients with previous Leflunomide administration (after at least 6 month wash out period from date of baseline visit) who will be prescribed Leflunomide at the sole decision of the treating physician.
4. Patients with or without another DMARDs including Methotrexate, Sulfasalazine and/or Hydroxychloroquine with or without steroids use who experienced therapy resistance, inadequate response or intolerance.
5. Patients read, understand and signed informed consent prior to inclusion.
6. Patients willing to complete and literate in the language of the available Health Assessment Questionnaire (HAQ Disability Index) either alone or with minimal assistance from caregivers and/or trained site personnel.

Exclusion Criteria:

1. Female patients who are pregnant or lactating at the time of inclusion or those who are planning for pregnancy within the coming year from the time of inclusion to the study.
2. Patients with contraindications to active constituent of Leflunomide.
3. Patients with severe concurrent infection (necessitating IV antibiotics or hospitalization).
4. Patients with history of non-treated hepatitis B &/or C infection.
5. Patients with history of severe liver disease (child C class).
6. Patients with history of severe renal insufficiency (creatinine clearance ≤30 ml/min.).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Egypt

Administrative Information

• NCT Number: NCT03599986
• Other Study ID Numbers: EVA_CLEAR_11022017
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided
• Plan Description: Not yet

• Current Responsible Party: Adel Mahmoud Elsayed, Eva Pharma
• Original Responsible Party: Same as current
• Current Study Sponsor: Eva Pharma
• Original Study Sponsor: Same as current
• Collaborators: DataClin

Investigators

• Principal Investigator: Adel Elsayed, MD; Professor, Department of Internal Medicine, Rheumatology and Immunology, Ain Shams University; Egypt

• PRS Account: Eva Pharma
• Verification Date: June 2020