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PK, PD, Safety, and Efficacy of SAIT101 Versus MabThera® Versus Rituxan® in Patients With Rheumatoid Arthritis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02819726
Recruitment Status : Completed
First Posted : June 30, 2016
Last Update Posted : December 6, 2018
Information provided by (Responsible Party):
Archigen Biotech Limited

Brief Summary:
This is a randomized, double-blind, parallel group, multicenter study to compare the PK, PD, safety, efficacy, tolerability, and immunogenicity of SAIT101 versus MabThera® versus Rituxan® in patients with RA. This study will take place globally across approximately 75 study centers in order to randomize approximately 282 patients. The study consists of Part A from baseline for PK and efficacy analysis, followed by Part B from Week 24 to 52 for safety follow-up in which collects transition data.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Biological: SAIT101 Biological: MabThera Biological: Rituxan Biological: Rituxan/SAIT101 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 294 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

In Part A, patients are randomized in a 1:1:1 ratio to receive one course (baseline and Week 2) of SAIT101 (n=94) versus Rituxan® (n=94) versus MabThera® (n=94).

At Week 24, patients are evaluated for the second course (Week 24 and 26) of the infusion.

In Part B, eligible patients in the SAIT101 arm receive the second course of SAIT101 treatment. Eligible patients in the MabThera® arm receive the second course of MabThera® treatment. Eligible patients in the Rituxan® arm are randomized in a 1:1 ratio to receive SAIT101 or Rituxan® treatment. Patients are followed up for safety until Week 52.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Parallel Group, Multicenter Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of SAIT101 Versus MabThera® Versus Rituxan® in Patients With Rheumatoid Arthritis (RA)
Actual Study Start Date : October 31, 2016
Actual Primary Completion Date : April 30, 2018
Actual Study Completion Date : November 7, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Rituximab

Arm Intervention/treatment
Experimental: SAIT101 Biological: SAIT101
1,000 mg i.v. of SAIT101 on Day 1 and 15. 1,000 mg i.v. of SAIT101 on week 24 and 26 for eligible patients.

Active Comparator: Rituxan Biological: Rituxan
1,000 mg i.v. of Rituxan® on Day 1 and 15. 1,000 mg i.v. of Rituxan® on week 24 and 26 for eligible patients.
Other Name: Rituximab

Active Comparator: MabThera Biological: MabThera
1,000 mg i.v. of MabThera® on Day 1 and 15. 1,000 mg i.v. of MabThera® on week 24 and 26 for eligible patients.
Other Name: Rituximab

Active Comparator: Rituxan/SAIT101 Biological: Rituxan/SAIT101
1,000 mg i.v. of Rituxan® on Day 1 and 15. 1,000 mg i.v. of SAIT101 on week 24 and 26 for eligible patients.

Primary Outcome Measures :
  1. Primary PK endpoint (AUC0-t) [ Time Frame: Immediately predose on Day 1 to last quantifiable concentration ]
    Area under the concentration-time curve from time 0 (immediately predose on Day 1) to last quantifiable concentration (AUC0-t)

  2. Area under the plasma concentration versus time curve(AUC0- ∞ (infinity)) [ Time Frame: Week 24 ]
    AUC from time 0 to infinity (AUC0 - ∞ (infinity))

  3. Area under the plasma concentration versus time curve(AUC0-D15) [ Time Frame: 0 to Day15 ]
    AUC from time 0 to Day 15 prior to infusion (AUC0-D15)

  4. Peak Plasma Concentration (Cmax) after Day 15 infusion [ Time Frame: After Day 15 ]
    Maximum Concentration (Cmax) after Day 15 infusion

  5. Trough concentration (Ctrough) before the second infusion on Day 15 [ Time Frame: Before the second infusion on Day 15 ]
    Trough concentration (Ctrough) before the second infusion on Day 15

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

1. Severe RA defined as:

  • Diagnosis of RA according to the revised (1987) ACR criteria for the classification of RA for at least 3 months prior to screening visit (see Appendix 3).
  • And ≥6 swollen joints and ≥6 tender/painful joints (from the 66/68 joint count system).
  • And C-reactive protein (CRP) ≥1.0 mg/dL or an ESR ≥28 mm/hour at Screening.
  • And positive RF (≥20 units/mL) or anti CCP antibodies (≥10 units/mL) at Screening.

    2. Patients with severe RA who have had an inadequate response to at least 3 months' treatment (according to the approved treatment and dosage) or intolerance (at Investigator's discretion and/or experience of intolerable AE or toxicity such as infusion related reaction, hypersensitivity, anaphylaxis or severe toxicity) to anti-TNF therapy (experience of severe AE or toxicity).

    3. Current treatment for RA on an outpatient basis:

  • Receiving MTX 7.5 - 25mg/week (oral or parenteral) for at least 12 weeks, including the last 4 weeks prior to Day 1 at a stable dose, via the same route of administration, dose, and formulation. Patients receiving a lower dose of MTX (<10 mg/week), stable for 4 weeks prior to Day 1, should be doing so as a result of a documented evidence of intolerance to higher doses of MTX.

Exclusion Criteria:

  1. Females who are pregnant, breastfeeding, or planning a pregnancy during the Treatment Period of and 12 months after the last infusion of study drug.
  2. Class IV as per the Classification of Global Functional Status in Rheumatoid Arthritis (as per ACR 1991 Revised Criteria) (see Appendix 4) or wheelchair/bed bound.
  3. History of or current inflammatory joint disease other than RA (including but not limited to gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy or Lyme disease).
  4. History of or current systemic autoimmune disorder (including but not limited to systemic lupus erythematosus, inflammatory bowel disease, pulmonary fibrosis, Felty syndrome, scleroderma, inflammatory myopathy, fibromyalgia, juvenile idiopathic arthritis, mixed connective tissue disease, vasculitis or other overlap syndrome), with the exception of the secondary Sjögren's syndrome.
  5. Primary or secondary immunodeficiency (history of, or currently active), including known history of human immunodeficiency virus (HIV) infection or positive test at screening.
  6. History of opportunistic infection.
  7. History of deep space/tissue infection (e.g., fasciitis, abscess, osteomyelitis) and infected prosthetic joint.
  8. Active infection of any kind (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. anti infective agents within 4 weeks prior to Screening or oral anti-infective agents within 2 weeks prior to Screening or use of antibiotic therapy three or more times in the last six months prior to Screening
  9. Positive serological test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C serology.

    • Patients with a negative HBsAg and positive HBcAb must have a hepatitis B virus (HBV) deoxyribonucleic acid (DNA) level <20 IU/mL (or 112 copies/mL) by polymerase chain reaction (PCR). These HBV patients must be willing to undergo monthly PCR HBV DNA testing during treatment and may participate following consultation with a hepatitis expert regarding monitoring and use of HBV antiviral therapy, and provided they agree to receive treatment as indicated. An HBV re-test will be performed monthly including Day 1, Weeks 4, 8, 12, 16, 20, 24, 36, 52, and unscheduled visit if required.

    • Patients with a positive test because of HBV vaccine may be included (i.e., anti-HBs+ and anti HBc-).
    • Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV ribonucleic acid (RNA).
  10. Confirmed current active tuberculosis (TB). • Patients with latent TB as determined by positive QuantiFERON-TB test may be enrolled if such patients have written confirmation from health care provider (e.g., Pulmonologist or Infection Specialist) of adequate prophylaxis before or within the screening period and no evidence of tuberculosis on a chest X-ray performed within 3 months from Day 1.

    • Screening period can be extended to 60 days for prophylaxis of latent TB.
    • QuantiFERON-TB test can be re-tested, if inconclusive.
  11. Any significant cardiac disease (e.g., coronary artery disease with unstable angina, coronary heart failure New York Heart Association Class III and IV, familial long QT syndrome, uncontrolled cardiac disease).
  12. History of moderate to severe chronic obstructive pulmonary disease (COPD) and/or history of severe COPD exacerbation(s) within the last 12 months of Screening.
  13. Vaccination with live or attenuated vaccines within 6 weeks prior to first dose of study drug or planned administration during study participation or within 4 weeks following last dose of study drug. Treatment with IV Gamma Globulin or the Prosorba® Column within 6 months prior to Day 1.
  14. History of a severe allergic reaction or anaphylactic reaction to a biological agent or history of hypersensitivity to any component of the study drug including known hypersensitivity or allergy to a murine product.
  15. Hypogammaglobulinemia at screening (IgG <600 mg/dL).
  16. Patients with hemoglobin <8.5 g/dL, ANC <1,500 cells/µL or platelet count <75,000 cells/µL at Screening. If a patient has findings marginally below this limit, re testing is allowed, at the Investigator's discretion, within the 30 day period between Visit 1 and Visit 2.

• Creatinine clearance < 50 mL/min (Cockroft-Gault formula)

• Liver function: Total bilirubin >2.0 mg/dL (>34 µmol/L) except for patients with Gilbert's Syndrome or hemolysis. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >3 × upper limit of normal (ULN). Patients with total bilirubin >2.0 mg/dL possibly due to Gilbert's Syndrome should have a direct bilirubin checked. If the direct bilirubin is normal and medical history is suggestive/positive for Gilbert's Syndrome, the patient successfully meets the criteria.

The AST and ALT may be repeated once within the Screening period if the initial result exceeds this limit, and the lesser value accepted if it meets this criterion.

18. History of cancer within the last 5 years prior to Screening, treated with anti-cancer chemotherapy, including solid tumors and hematologic malignancies and carcinoma in situ (except basal cell and squamous cell carcinomas of the skin or carcinoma in situ of the cervix uteri that have been excised and cured).

19. Major surgical procedure within 4 weeks prior to or planned within 24 weeks of Day 1, with the exception of surgical procedures for dental prosthesis.

20. Previous treatment with a B cell modulating or B cell depletion therapy, such as, but not limited to rituximab, belimumab, atacicept, tabalumab, ocrelizumab, ofatumumab, obinutuzumab, epratuzumab and other experimental treatments.

21. Injectable corticosteroids within 6 weeks prior to Day 1.

22. Participation in a previous clinical study within 4 weeks of Screening or having received treatment with a drug that has not received regulatory approval for any indication within a minimum of 5 half-lives prior to Day 1.

23. Patients who, based on the Investigator's judgment, have a clinically significant or unstable medical or surgical condition that may preclude safe and complete study participation. Conditions may also include cardiovascular, vascular, pulmonary, hepatic, renal, endocrine or neurological conditions as determined by medical history, physical examination, laboratory tests or electrocardiogram (ECG).

24. Patients who, in the judgment of the Investigator, are likely to be non-compliant or uncooperative during the study.

25. History of substance abuse (alcohol or drug).

26. History of demyelinating disorders (such as multiple sclerosis or Guillain-Barré syndrome).

27. Patients at risk of PML:

  • Patients with immune deficiency such as transplant patients on immunosuppressive medications
  • Patients receiving certain kinds of chemotherapy
  • Patients receiving natalizumab (Tysabri®) for multiple sclerosis
  • Patients with psoriasis on longer term efalizumab (Raptiva®) or patients with acquired immunodeficiency syndrome (AIDS)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02819726

  Show 75 Study Locations
Sponsors and Collaborators
Archigen Biotech Limited

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Responsible Party: Archigen Biotech Limited Identifier: NCT02819726     History of Changes
Other Study ID Numbers: AGB001
First Posted: June 30, 2016    Key Record Dates
Last Update Posted: December 6, 2018
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Archigen Biotech Limited:
an inadquate response to anti -TNF therapy
Additional relevant MeSH terms:
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Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents