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Completed

NCT Number: NCT02287922

A Phase IIb Study for ALX-0061 Monotherapy in Subjects With Rheumatoid Arthritis

The primary objective of this study is:

- To assess the efficacy and safety of dose regimens of ALX-0061 monotherapy administered subcutaneously (s.c.) to subjects with active rheumatoid arthritis (RA).

The secondary objectives of this study are:

* To assess the effects of ALX-0061 on quality of life, the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of ALX-0061 and to explore potential dose regimens for ALX-0061 monotherapy, based on safety and efficacy, for further clinical development. * To obtain parallel descriptive information concerning the efficacy and safety of tocilizumab (TCZ) s.c. in the same clinical trial RA population.

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Key information

Conditions

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

Age range

18 year–74 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Investigator Site, Brussels, Belgium

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Diagnosis of RA (according to the 2010 EULAR/American College of Rheumatology (ACR) classification criteria) for at least 6 months prior to screening, and ACR functional class I-III.
  • Received previous or current treatment with methotrexate (MTX), and is considered intolerant to MTX, or for whom continued treatment with MTX is inappropriate or has contraindications for MTX use.
  • Subjects must not have received MTX for at least 4 weeks before first administration of the study drug.
  • Have active RA with at least 6 swollen and 6 tender joints(66/68 joint count) at the time of screening and baseline
  • Others as defined in the protocol

Exclusion criteria

  • Have been treated with DMARDs (Disease Modifying Antirheumatic Drugs)/systemic immunosuppressive drugs during the 4 weeks, or 12 weeks for hydroxychloroquine, chloroquine, or leflunomide (except when an adequate wash-out procedure for leflunomide was completed), prior to first administration of study drug.
  • Have received approved or investigational biological or targeted synthetic DMARD therapies for RA (including tumor necrosis factor alpha-inhibitors, abatacept, rituximab, or Janus kinase [JAK]-inhibitors) less than 6 months prior to screening.
  • Have a history of toxicity, non-tolerance, primary non-response or inadequate response to a biological therapy, or targeted synthetic DMARDs (including JAK inhibitors), for RA.
  • Have received prior therapy blocking the interleukin-6 (IL-6) pathway, at any time.
  • Others as defined in the protocol.

Treatment and study plan

ALX-0061

Biological

Placebo

Biological

Tocilizumab

Biological

Primary outcomes

  1. Number and Percentage of Subjects With American College of Rheumatology 20 (ACR20) at Week 12

    Time frame: Week 12

    ACR 20 response is defined as:

    • 20% improvement in tender joint count (TJC; 68 joints) relative to Week 0 AND
    • 20% improvement in swollen joint count (SJC; 66 joints) relative to Week 0 AND
    • 20% improvement in 3 of the following 5 areas relative to Week 0:
    • Subject's Assessment of Pain (100 mm - visual analogue scale [VAS])
    • Subject's Global Assessment of Disease Activity (VASPA)
    • Physician's Global Assessment of Disease Activity (VASPHA)
    • Subject's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI)
    • C-reactive protein (CRP) level

    The primary endpoint was analyzed using non-responder imputation (NRI), i.e., subjects with missing ACR20 response at Week 12 were treated as non-responders.

Secondary outcomes

  1. Number and Percentage of Subjects With ACR50 and ACR70 Response at Week 12

    Time frame: Week 12

    ACR50/70 response is defined as:

    • 50/70% improvement in TJC (68 joints) relative to Week 0 AND
    • 50/70% improvement in SJC (66 joints) relative to Week 0 AND
    • 50/70% improvement in 3 of the following 5 areas relative to Week 0:
    • Subject's Assessment of Pain (100 mm - VAS)
    • Subject's Global Assessment of Disease Activity (VASPA)
    • Physician's Global Assessment of Disease Activity (VASPHA)
    • Subject's assessment of physical function as measured by HAQ-DI
    • CRP level

    This endpoint was analyzed using NRI, i.e., subjects with missing response at Week 12 were treated as non-responders.

  2. Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score Using 28 Joint Counts (DAS28) Using C-reactive Protein (CRP) at Week 12

    Time frame: Week 12

    DAS28(CRP) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.36 × ln[CRP+1]) + (0.014 × VASPA) + 0.96

    Low disease activity = 2.6 ≤ DAS28 ≤ 3.2

    Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

  3. Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Week 12

    Time frame: Week 12

    DAS28(ESR) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.70 × ln[ESR]) +(0.014 × VASPA)

    Low disease activity = 2.6 ≤ DAS28 ≤ 3.2

    Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

  4. Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Week 12

    Time frame: Week 12

    SDAI = TJC28 + SJC28 + VASPA + VASPHA + CRP (mg/dL)

    Low disease activity: 3.3 < SDAI ≤ 11.0

    Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using non-responder imputation (NRI), i.e., subjects with missing response at the concerned visit were treated as non-responders.

  5. Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Week 12

    Time frame: Week 12

    CDAI = TJC28 + SJC28 + VASPA + VASPHA

    Low disease activity: 2.8 < CDAI ≤ 10

    Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

  6. Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Week 12

    Time frame: Week 12

    EULAR good response is defined as an improvement of >1.2 in DAS28 (CRP) relative to baseline.

    This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

  7. Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Week 12

    Time frame: Week 12

    DAS28(ESR) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.70 × ln[ESR]) +(0.014 × VASPA)

    Remission = DAS28(ESR) < 2.6

    This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

  8. Number and Percentage of Subjects in Remission Using SDAI at Week 12

    Time frame: Week 12

    SDAI = TJC28 + SJC28 + VASPA + VASPHA + CRP (mg/dL)

    Remission: SDAI ≤ 3.3

    This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

  9. Number and Percentage of Subjects in Remission Using CDAI at Week 12

    Time frame: Week 12

    CDAI = TJC28 + SJC28 + VASPA + VASPHA

    Remission: CDAI ≤ 2.8

    This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

  10. Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Week 12

    Time frame: Week 12

    Boolean remission: tender joint count (TJC)28 ≤ 1 and swollen joint count (SJC)28 ≤ 1 and VASPA (cm) ≤ 1 and CRP (mg/dL) ≤ 1

    This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

  11. Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12

    Time frame: From baseline until Week 12

    The HAQ-DI is a 20-question instrument which assesses the degree of difficulty the subject had in accomplishing tasks in 8 functional areas over the previous week. The 8 areas are: dressing and grooming, hygiene, arising, reach, eating, grip, walking, common daily activities. Within each area, subjects report the amount of difficulty they have in performing the specific items. There are 4 response options ranging from: 0 = No Difficulty, 1 = With Some Difficulty, 2 = With Much Difficulty, 3 = Unable to Do. The 8 areas are each given a single score equal to the maximum value of their component activities (0, 1, 2, or 3). The sum of the area scores is then divided by the number of areas answered to obtain the final HAQ score (rounded to the nearest value evenly divisible by 0.125). The final HAQ-DI score ranges from 0 to 3. A high score means a high degree of disability (=worse outcome).

    Missing values were imputed with the last non-missing observation.

  12. Change From Baseline in Physical and Mental Component Scores of Short Form Health Survey (SF-36) at Week 12

    Time frame: From baseline until week 12

    The Short Form (36) Health Survey (SF-36) consists of 36 items that can be summarized into 8 domains: physical functioning, role limitations due to physical health problems (role-physical), bodily pain, general health, vitality, social functioning, role limitations due to emotional problems (role-emotional), and mental health. Two summary measures, the physical component summary and the mental component summary, can be derived based on these domain scores. Each score is directly transformed into a 0-100 score on the assumption that each question carries equal weight. Low score indicates greater disability.

  13. Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Week 12

    Time frame: From baseline until Week 12

    The FACIT Measurement System is a collection of health-related quality of life questionnaires that assess multidimensional health status in people with various chronic illnesses. The FACIT Fatigue Scale is a short, 13-item, easy to administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four point Likert scale (4 = not at all fatigued to 0 = very much fatigued). To score the FACIT-fatigue, all items are summed to create a single fatigue score with a range from 0 to 52. Items are reverse scored when appropriate to provide a scale in which higher scores represent better functioning or less fatigue.

  14. Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R)

    Time frame: From baseline until Week 12

    Values below the limit of quantification are imputed with the lower limit of quantification (LLOQ).

  15. Pharmacokinetics: ALX-0061 Concentration in Serum at Week 12

    Time frame: From baseline until Week 12

  16. Number and Percentage of Subjects With Development of a Treatment-emergent Antidrug Antibody Response

    Time frame: From first study drug intake up to and including follow-up (FU), i.e., maximum of 22 weeks (10 weeks of treatment + 12 weeks of FU)

  17. Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity

    Time frame: From baseline until Week 12

  18. Number of Treatment-emergent Adverse Event by Severity

    Time frame: From baseline until Week 12

  19. Number and Percentage of Subjects With a Treatment-related Treatment-emergent Adverse Event

    Time frame: From baseline until Week 12

    treatment related = considered at least possibly related to study drug by the Investigator

  20. Number of Treatment-related Treatment-emergent Adverse Event

    Time frame: From baseline until Week 12

    treatment related = considered at least possibly related to study drug by the Investigator

Sponsors and collaborators

Lead sponsor

Ablynx, a Sanofi company

Industry

Registry information

Official study title

A Phase IIb Multicenter, Randomized, Double-blind Study of ALX-0061 Administered Subcutaneously as Monotherapy, in Subjects With Moderate to Severe Rheumatoid Arthritis Who Are Intolerant to Methotrexate or for Whom Continued Methotrexate Treatment is Inappropriate

Important dates

Study start
2015
Primary completion
2016
Study completion
2016
First posted
Nov 11, 2014
Registry last updated
Aug 21, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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