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

August 6, 2019 updated by: Ablynx

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

251

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium, 1200
        • Investigator site
      • Ghent, Belgium, 9000
        • Investigator site
      • Liège, Belgium, 4000
        • Investigator site
  • Bulgaria
      • Burgas, Bulgaria
        • Investigator site
      • Pleven, Bulgaria
        • Investigator site
      • Plovdiv, Bulgaria
        • Investigator Site 1
      • Plovdiv, Bulgaria
        • Investigator Site 2
      • Ruse, Bulgaria
        • Investigator Site 2
      • Ruse, Bulgaria
        • Investigator Site 1
      • Sofia, Bulgaria
        • Investigator site
  • Czechia
      • Brno, Czechia, 602000
        • Investigator site
      • Olomouc, Czechia
        • Investigator site
      • Ostrava, Czechia, 70300
        • Investigator site
      • Prague, Czechia
        • Investigator Site 1
      • Prague, Czechia
        • Investigator Site 2
      • Zlin, Czechia
        • Investigator site
  • Georgia
      • Tbilisi, Georgia, 0102
        • Investigator site
      • Tbilisi, Georgia, 0159
        • Investigator Site 1
      • Tbilisi, Georgia, 0159
        • Investigator Site 2
      • Tbilisi, Georgia, 0160
        • Investigator site
      • Tbilisi, Georgia, 0179
        • Investigator site
  • Germany
      • Berlin, Germany
        • Investigator site
      • Frankfurt, Germany
        • Investigator site
      • Hamburg, Germany
        • Investigator site
  • Hungary
      • Baja, Hungary, 6500
        • Investigator site
      • Budapest, Hungary
        • Investigator site
      • Esztergom, Hungary
        • Investigator site
      • Gyula, Hungary, 5700
        • Investigator site
      • Szikszo, Hungary, 3800
        • Investigator site
      • Szombathely, Hungary, 9700
        • Investigator site
      • Székesfehérvar, Hungary, 8000
        • Investigator site
      • Veszprém, Hungary, 8200
        • Investigator site
  • Mexico
      • Culiacan, Mexico
        • Investigator site
      • Leon, Mexico
        • Investigator site
      • Mexico City, Mexico
        • Investigator Site 1
      • Mexico City, Mexico
        • Investigator Site 2
      • Mexico City 1, Mexico
        • Investigator site
      • Monterrey, Mexico
        • Investigator Site 1
      • Monterrey, Mexico
        • Investigator Site 2
  • Moldova, Republic of
      • Chisinau, Moldova, Republic of, 2025
        • Investigator site
      • Chisinau, Moldova, Republic of
        • Investigator site
  • North Macedonia
      • Skopje, North Macedonia, 1000
        • Investigator Site 1
      • Skopje, North Macedonia, 1000
        • Investigator Site 2
  • Poland
      • Bydgoszcz, Poland
        • Investigator site
      • Elblag, Poland, 82300
        • Investigator Site 2
      • Elblag, Poland
        • Investigator site
      • Gdynia, Poland
        • Investigator site
      • Grodzisk Mazowiecki, Poland, 05825
        • Investigator site
      • Lublin, Poland, 20582
        • Investigator site
      • Poznan, Poland, 60773
        • Investigator site
      • Sochaczew, Poland, 96500
        • Investigator site
      • Torun, Poland, 87100
        • Investigator site
      • Warszawa, Poland, 02653
        • Investigator site
  • Romania
      • Bucharest, Romania
        • Investigator site
      • Oradea, Romania
        • Investigator site
      • Timisoara, Romania
        • Investigator site
  • Serbia
      • Belgrade, Serbia
        • Investigator Site 1
      • Belgrade, Serbia
        • Investigator Site 2
      • Belgrade, Serbia
        • Investigator Site 3
      • Niska Banja, Serbia
        • Investigator site
  • Spain
      • Cordoba, Spain
        • Investigator site
      • Madrid, Spain, 28007
        • Investigator site
      • Santander, Spain, 39300
        • Investigator site
      • Santander, Spain
        • Investigator Site 2
      • Santiago de Compostela, Spain
        • Investigator Site 1
      • Santiago de Compostela, Spain
        • Investigator Site 2
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35216
        • Investigator site
    • California
      • Hemet, California, United States, 92543
        • Investigator site
      • La Palma, California, United States, 90712
        • Investigator site
      • Los Angeles, California, United States, 90017
        • Investigator site
      • Los Angeles, California, United States, 90036
        • Investigator site
      • Ventura, California, United States, 93003
        • Investigator site
    • Florida
      • Hialeah, Florida, United States, 33016
        • Investigator site
      • Homestead, Florida, United States, 33030
        • Investigator site
      • Orlando, Florida, United States, 32804
        • Investigator site
    • Georgia
      • Stockbridge, Georgia, United States, 30281
        • Investigator site
    • Kansas
      • Overland Park, Kansas, United States, 66209
        • Investigator site
    • Massachusetts
      • Worcester, Massachusetts, United States, 01605
        • Investigator site
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • Investigator site
    • New York
      • New York, New York, United States, 10018
        • Investigator site
    • South Carolina
      • Charleston, South Carolina, United States, 29406
        • Investigator site
    • Tennessee
      • Memphis, Tennessee, United States, 38119
        • Investigator site
    • Texas
      • Mesquite, Texas, United States, 75150
        • Investigator site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 74 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ALX-0061 150 mg q4w
ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.
Biological: Placebo
Biological: ALX-0061
Experimental: ALX-0061 150 mg q2w
ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.
Biological: Placebo
Biological: ALX-0061
Experimental: ALX-0061 225 mg q2w
ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.
Biological: ALX-0061
Active Comparator: TCZ 162 mg q1w or q2w
Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).
Biological: Tocilizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Week 12
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.
Week 12
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.
Week 12
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.
Week 12
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.
Week 12
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.
Week 12
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.
Week 12
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.
Week 12
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.
Week 12
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.
Week 12
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.
From baseline until Week 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.
From baseline until week 12
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.
From baseline until Week 12
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).
From baseline until Week 12
Pharmacokinetics: ALX-0061 Concentration in Serum at Week 12
Time Frame: From baseline until Week 12
From baseline until Week 12
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)
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)
Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity
Time Frame: From baseline until Week 12
From baseline until Week 12
Number of Treatment-emergent Adverse Event by Severity
Time Frame: From baseline until Week 12
From baseline until Week 12
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
From baseline until Week 12
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
From baseline until Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ablynx

Investigators

  • Study Director: Medical Monitor, MD, Ablynx

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2015

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

July 1, 2016

Study Registration Dates

First Submitted

November 5, 2014

First Submitted That Met QC Criteria

November 10, 2014

First Posted (Estimate)

November 11, 2014

Study Record Updates

Last Update Posted (Actual)

August 21, 2019

Last Update Submitted That Met QC Criteria

August 6, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALX0061-C202
  • 2014-003012-36 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Rheumatoid Arthritis

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Lebanon

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe