Clinical trial NCT02518620: An Open-Label Extension Study Assessing the Long-Term Efficacy and Safety of ALX-0061 in Subjects With Rheumatoid Arthritis
Official title: A Phase II Multicenter, Open-Label Extension Study Assessing the Long-Term Efficacy and Safety of Subcutaneous ALX-0061 in Subjects With Moderate to Severe Rheumatoid Arthritis Who Have Completed One of the Preceding Phase IIb Studies With ALX-0061
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Ablynx, a Sanofi company
Sponsor class: INDUSTRY
First posted: 2015-08-10
Enrollment: 406
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Detailed description: Eligible subjects received one of the following treatments during the preceding Phase IIb studies ALX0061-C201 and ALX0061-C202:

* Study ALX0061-C201:

  * Placebo (+ methotrexate \[MTX\]), or
  * ALX-0061 75 mg every 4 weeks (q4w) (+ MTX), or
  * ALX-0061 150 mg q4w (+ MTX), or
  * ALX-0061 150 mg every 2 weeks (q2w) (+ MTX), or
  * ALX-0061 225 mg q2w (+ MTX), for 24 weeks
* Study ALX0061-C202:

  * ALX-0061 150 mg q4w, or
  * ALX-0061 150 mg q2w, or
  * ALX-0061 225 mg q2w, for 12 weeks

At the Week 24 (ALX0061-C201) or Week 12 (ALX0061-C202) visit of the previous study, informed consent was obtained from all subjects who were deemed potentially eligible for the OLE study, according to the inclusion and exclusion criteria. This was marked as the Week 0 visit of the C203 study. Of note, the Baseline time point in the analyses of this study was defined the Baseline value of the parent study.

In this OLE study, eligible subjects received ALX-0061 150 mg s.c. injections, beginning at Week 0 and every 2 weeks thereafter, up to and including Week 102. Eligible subjects from the preceding study ALX0061-C201 also continued their MTX treatment.

Maintenance of the response (i.e., at least 20% improvement in both SJC and TJC compared to Baseline of the preceding study) was reassessed at the study visits at Weeks 12, 24, 36, 48, 60, 72, 84, and 96. Subjects who failed to maintain response and met the Efficacy Discontinuation Criteria were discontinued from this study.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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:

  1. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels ≥ 2 times the upper limit of normal (ULN).
  2. Hemoglobin levels ≤ 85 g/L (8.5 g/dL).
  3. Platelet count ≤ 75 x 109/L (75,000 cells/mm³).
  4. Absolute neutrophil count \< 1.5 x 109/L.
  5. Serum creatinine levels ≥ 1.5 mg/dL (133 μmol/L).
  6. Any other clinically significant abnormal laboratory result as evaluated by the Investigator.
  7. If no laboratory test results of the Week 22 Visit (for subjects participating in the preceding ALX0061-C201 study) or the Week 10 Visit (for subjects participating in the preceding ALX0061-C202 study) were available, then laboratory values of tests performed between Week 22 and 24 (for study ALX0061-C201) or Week 10 and 12 (for study ALX0061-C202) were taken into account for the exclusion criteria a to e listed above.

Primary outcomes:
measure: Number and Percentage of Subjects With American College of Rheumatology (ACR) 20 Response.
timeFrame: At Weeks 0, 12, 48, and 104
measure: Number and Percentage of Subjects With ACR50 Response.
timeFrame: At Weeks 0, 12, 48, and 104
measure: Number and Percentage of Subjects With ACR70 Response.
timeFrame: At Weeks 0, 12, 48, and 104
measure: ACR-N Index of Improvement
timeFrame: At Weeks 0, 12, 48, and 104
measure: 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)
timeFrame: At Weeks 0, 12, 48, and 104
measure: Number and Percentage of Subjects With DAS28 Using C-reactive Protein (CRP) < 2.6, Low, Moderate or High Disease Activity Based on DAS28(CRP)
timeFrame: At Weeks 0, 12, 48, and 104
Secondary outcomes:
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Investigator Site 1
city: Brussels
country: Belgium
facility: Investigator Site 2
city: Ghent
country: Belgium
facility: Investigator Site
city: Liège
country: Belgium
facility: Investigator Site
city: Burgas
country: Bulgaria
facility: Investigator Site
city: Pleven
country: Bulgaria
facility: Investigator site
city: Plovdiv
country: Bulgaria
facility: Investigator Site
city: Ruse
country: Bulgaria
facility: Investigator Site
city: Sofia
country: Bulgaria
facility: Investigator Site 1
city: Sofia
country: Bulgaria
facility: Investigator Site 2
city: Tbilisi
country: Georgia
facility: Investigator Site 1
city: Tbilisi
country: Georgia
facility: Investigator Site 2
city: Tbilisi
country: Georgia
facility: Investigator Site 3
city: Tbilisi
country: Georgia
facility: Investigator Site 4
city: Tbilisi
country: Georgia
facility: Investigator Site 5
city: Hamburg
country: Germany
facility: Investigator Site
city: Baja
country: Hungary
facility: Investigator Site
city: Balatonfüred
country: Hungary
facility: Investigator site
city: Bekescsaba
country: Hungary
facility: Investigator site
city: Gyula
country: Hungary
facility: Investigator Site
city: Szikszó
country: Hungary
facility: Investigator Site
city: Szombathely
country: Hungary
facility: Investigator Site
city: Székesfehérvar
country: Hungary
facility: Investigator Site
city: Veszprém
country: Hungary
facility: Investigator Site
city: Culiacán
country: Mexico
facility: Investigator site
city: León
country: Mexico
facility: Investigator site
city: Mexico City
country: Mexico
facility: Investigator site 1
city: Mexico City
country: Mexico
facility: Investigator site 2
city: Monclova
country: Mexico
facility: Investigator site
city: Monterrey
country: Mexico
facility: Investigator site 1
city: Monterrey
country: Mexico
facility: Investigator site 2
city: Mérida
country: Mexico
facility: Investigator site
city: Chisinau
country: Moldova, Republic of
facility: Investigator Site 1
city: Chisinau
country: Moldova, Republic of
facility: Investigator site 2
city: Skopje
country: North Macedonia
facility: Investigator Site 1
city: Skopje
country: North Macedonia
facility: Investigator Site 2
city: Bydgoszcz
country: Poland
facility: Investigator Site
city: Elbląg
country: Poland
facility: Investigator site 1
city: Elbląg
country: Poland
facility: Investigator site 2
city: Gdynia
country: Poland
facility: Investigator Site
city: Grodzisk
country: Poland
facility: Investigator Site
city: Katowice
country: Poland
facility: Investigator Site
city: Lublin
country: Poland
facility: Investigator Site
city: Poznan
country: Poland
facility: Investigator Site
city: Sochaczew
country: Poland
facility: Investigator Site
city: Torun
country: Poland
facility: Investigator Site
city: Warszawa
country: Poland
facility: Investigator Site 1
city: Warszawa
country: Poland
facility: Investigator Site 2
city: Galați
country: Romania
facility: Investigator site
city: Oradea
country: Romania
facility: Investigator site
city: Belgrade
country: Serbia
facility: Investigator Site 1
city: Belgrade
country: Serbia
facility: Investigator Site 2
city: Belgrade
country: Serbia
facility: Investigator site 3
city: Niska Banja
country: Serbia
facility: Investigator Site
city: Madrid
country: Spain
facility: Investigator site
city: Santander
country: Spain
facility: Investigator Site
city: Santiago de Compostela
country: Spain
facility: Investigator Site
Study officials:
affiliation: Ablynx NV
name: Medical Monitor
role: STUDY_DIRECTOR
References: