An Open-Label Extension Study Assessing the Long-Term Efficacy and Safety of ALX-0061 in Subjects With Rheumatoid Arthritis

NCT02518620 | Completed Phase 2 Results DMC

• 2 other identifiers: ALX0061-C2032014-003034-42
• Study Type: interventional
• Target: 406
• Locations: 12 countries
• Sites: 57

Brief Summary

This was a multicenter, open-label extension (OLE) Phase II study designed to evaluate the long-term efficacy and safety of ALX-0061 (i.e., vobarilizumab) administered subcutaneously (s.c.) in subjects with active rheumatoid arthritis (RA) who had completed the treatment and assessment period of one of the preceding Phase IIb studies with ALX-0061 (ALX0061-C201 and ALX0061-C202; placebo and ALX-0061 treatment arms only), and who achieved at least 20% improvement in swollen joint count (SJC) and/or tender joint count (TJC) (66/68 counts) compared to Baseline at the final visit of the preceding study (i.e., Week 24 for Study ALX0061-C201 and Week 12 for Study ALX0061-C202).

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (6)

• Number and Percentage of Subjects With American College of Rheumatology (ACR) 20 Response.

  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 ACR20 responses were measured at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, and 104 and Weeks 0, 12, 48, and 104 reported.

  At Weeks 0, 12, 48, and 104

• Number and Percentage of Subjects With ACR50 Response.

  ACR50 response is defined as: * 50% improvement in TJC (68 joints) relative to Week 0 AND * 50% improvement in SJC (66 joints) relative to Week 0 AND * 50% 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 ACR50 responses were measured at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, and 104 and Weeks 0, 12, 48, and 104 reported.

  At Weeks 0, 12, 48, and 104

• Number and Percentage of Subjects With ACR70 Response.

  ACR70 response is defined as: * 70% improvement in TJC (68 joints) relative to Week 0 AND * 70% improvement in SJC (66 joints) relative to Week 0 AND * 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 ACR70 responses were measured at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, and 104 and Weeks 0, 12, 48, and 104 reported.

  At Weeks 0, 12, 48, and 104

• ACR-N Index of Improvement

  The ACR-N Index of Improvement is defined as the minimum of the following 3 criteria: * The percent improvement from Week 0 in TJCs * The percent improvement from Week 0 in SJCs * The median percent improvement from Week 0 for the following 5 assessments: * Subject's assessment of pain (VAS) * Subject's global assessment of disease activity (VASPHA) * Physician's global assessment of disease activity (VASPHA) * Subject's assessment of physical function as measured by the HAQ-DI * CRP level ACR-N Index of Improvement was measured at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, and 104 and Weeks 0, 12, 48, and 104 reported.

  At Weeks 0, 12, 48, and 104

• Number and Percentage of Subjects in Remission or With Low, Moderate or High Disease Activity Based on Disease Activity Score Using 28 Joint Counts (DAS28) Using Estimated Sedimentation Rate (ESR)

  DAS28(ESR) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.70 × ln\[ESR\]) +(0.014 × VASPA) * Remission = DAS28(ESR) \< 2.6 * Low disease activity = 2.6 ≤ DAS28 ≤ 3.2 * Moderate disease activity = 3.2 \< DAS28 ≤ 5.1 * High disease activity = DAS28 \> 5.1 Disease activity based on DAS28(ESR) was measured at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, and 104 and Weeks 0, 12, 48, and 104 reported.

  At Weeks 0, 12, 48, and 104

• Number and Percentage of Subjects With DAS28 Using C-reactive Protein (CRP) < 2.6, Low, Moderate or High Disease Activity Based on DAS28(CRP)

  DAS28(CRP) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.36 × ln\[CRP+1\]) + (0.014 × VASPA) + 0.96 * DAS28(CRP) \< 2.6 * Low disease activity = 2.6 ≤ DAS28 ≤ 3.2 * Moderate disease activity = 3.2 \< DAS28 ≤ 5.1 * High disease activity = DAS28 \> 5.1 Disease activity based on DAS28(CRP) was measured at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, and 104 and Weeks 0, 12, 48, and 104 reported.

  At Weeks 0, 12, 48, and 104

Study Arms (1)

ALX-0061 150 mg q2w (+ MTX)

EXPERIMENTAL

Biological: ALX-0061

Interventions

ALX-0061 BIOLOGICAL

Subjects received ALX-0061 150 mg s.c. injections, beginning at Week 0 and q2w thereafter, up to and including Week 102. Subjects from the preceding study ALX0061-C201 also continued their MTX treatment.

Also known as: Vobarilizumab

ALX-0061 150 mg q2w (+ MTX)

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have been eligible for one of the preceding Phase IIb studies with ALX-0061 (study ALX0061-C201 or ALX0061-C202), have been randomized to placebo or one of the ALX-0061 arms (subjects randomized to tocilizumab \[TCZ\] in study ALX0061-C202 were not eligible), and completed the entire treatment and assessment period of the preceding studies (i.e., 24 weeks for study ALX0061-C201 and 12 weeks for study ALX0061-C202).
• Must have reached at least 20% improvement in SJC and/or TJC (66/68 counts) compared to Week 0 at Week 24 for subjects participating in the preceding Phase IIb ALX0061 C201 study, or at Week 12 for subjects participating in the preceding Phase IIb ALX0061-C202 study
• Female subjects of childbearing potential (excluding postmenopausal women, sterilized, ovariectomized, and hysterectomized women) must agree to use 2 generally accepted adequate contraceptive methods of which 1 is a barrier method (e.g., hormonal contraception stabilized for at least 1 month \[oral, patch, depot, injectable, vaginal ring\] in combination with condom by partner) or should agree upon continuous abstinence from heterosexual contact from screening/baseline until at least 6 months after last dosing. Male subjects must use condoms for the duration of the study and for at least 6 months after last administration of study drug.
• Ability to comprehend and willingness to sign the informed consent form (ICF).
• An understanding of and ability and willingness to adhere to the study visit schedule and other protocol requirements.

You may not qualify if:

• Received TCZ during the previous Study ALX0061-C202.
• Received any prohibited treatment during the previous Phase IIb studies (ALX0061-C201 or ALX0061-C202.
• Diagnosis of or suspicion of a serious infection (requiring parental antibiotics and/or hospitalization) or tuberculosis during the preceding study.
• Diagnosis of malignancy or demyelinating disease during the preceding study.
• Any active or recurrent viral infection that made the subject unsuitable for the study based on the Investigator's clinical assessment, including recurrent/disseminated herpes zoster.
• Diagnosis of congestive heart failure class III or IV (as defined by the New York Heart Association), unstable angina pectoris, myocardial infarction, and/or cerebrovascular accident during the preceding study.
• Abnormality in laboratory test results observed at the Week 22 visit for subjects participating in the preceding Phase IIb ALX0061-C201 study, or observed at the Week 10 visit for subjects participating in the preceding Phase IIb ALX0061-C202 study:
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels ≥ 2 times the upper limit of normal (ULN).
• Hemoglobin levels ≤ 85 g/L (8.5 g/dL).
• Platelet count ≤ 75 x 109/L (75,000 cells/mm³).
• Absolute neutrophil count \< 1.5 x 109/L.
• Serum creatinine levels ≥ 1.5 mg/dL (133 μmol/L).
• Any other clinically significant abnormal laboratory result as evaluated by the Investigator.

Sponsors & Collaborators

• Ablynx, a Sanofi company: lead

Study Sites (57)

Investigator Site 1

Brussels, Belgium

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Investigator Site 2

Brussels, Belgium

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Ghent, Belgium

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Liège, Belgium

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Burgas, Bulgaria

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Pleven, Bulgaria

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Plovdiv, Bulgaria

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Rousse, Bulgaria

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Sofia, Bulgaria

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Sofia, Bulgaria

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Tbilisi, Georgia

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Tbilisi, Georgia

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Investigator Site 3

Tbilisi, Georgia

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Tbilisi, Georgia

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Investigator Site 5

Tbilisi, Georgia

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Hamburg, Germany

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Baja, Hungary

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Balatonfüred, Hungary

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Békéscsaba, Hungary

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Gyula, Hungary

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Székesfehérvar, Hungary

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Szikszó, Hungary

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Szombathely, Hungary

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Veszprém, Hungary

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Culiacán, Mexico

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León, Mexico

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Mexico City, Mexico

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Mexico City, Mexico

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Mérida, Mexico

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Monclova, Mexico

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Monterrey, Mexico

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Monterrey, Mexico

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Chisinau, Moldova

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Chisinau, Moldova

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Skopje, North Macedonia

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Skopje, North Macedonia

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Bydgoszcz, Poland

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Elblag, Poland

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Elblag, Poland

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Gdynia, Poland

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Grodzisk, Poland

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Katowice, Poland

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Lublin, Poland

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Poznan, Poland

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Sochaczew, Poland

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Torun, Poland

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Warsaw, Poland

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Warsaw, Poland

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Galați, Romania

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Oradea, Romania

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Belgrade, Serbia

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Belgrade, Serbia

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Investigator site 3

Belgrade, Serbia

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Niška Banja, Serbia

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Madrid, Spain

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Santander, Spain

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Santiago de Compostela, Spain

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MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

ALX-0061

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Medical Monitor
• Organization: Ablynx NV

clinicaltrials@ablynx.com

+32 (0)9 262 00 00

Study Officials

• Medical Monitor

  Ablynx NV

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2015
• First Posted: August 10, 2015
• Study Start: July 1, 2015
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: July 30, 2019
• Results First Posted: July 19, 2019

Record last verified: 2019-07

Locations

GE (5); MO (2); ME (8); NO (2); HU (8); SE (4); ES (3); BU (6); DE (1); PL (12); RO (2); BE (4)