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

Rheumatoid Arthritis Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02287922
• Other study ID #: ALX0061-C202
• Secondary ID: 2014-003012-36
• Status: Completed
• Phase: Phase 2
• Start date: March 2015
• Est. completion date: July 2016

Study information

• Verified date: August 2019
• Source: Ablynx
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 251
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• ALX-0061

• Placebo

• Tocilizumab

Locations

Country	Name	City	State
Belgium	Investigator Site	Brussels
Belgium	Investigator Site	Ghent
Belgium	Investigator Site	Liège
Bulgaria	Investigator Site	Burgas
Bulgaria	Investigator Site	Pleven
Bulgaria	Investigator Site 1	Plovdiv
Bulgaria	Investigator Site 2	Plovdiv
Bulgaria	Investigator Site 1	Ruse
Bulgaria	Investigator Site 2	Ruse
Bulgaria	Investigator Site	Sofia
Czechia	Investigator Site	Brno
Czechia	Investigator Site	Olomouc
Czechia	Investigator Site	Ostrava
Czechia	Investigator Site 1	Prague
Czechia	Investigator Site 2	Prague
Czechia	Investigator Site	Zlin
Georgia	Investigator Site	Tbilisi
Georgia	Investigator Site	Tbilisi
Georgia	Investigator Site	Tbilisi
Georgia	Investigator Site 1	Tbilisi
Georgia	Investigator Site 2	Tbilisi
Germany	Investigator Site	Berlin
Germany	Investigator Site	Frankfurt
Germany	Investigator Site	Hamburg
Hungary	Investigator Site	Baja
Hungary	Investigator Site	Budapest
Hungary	Investigator Site	Esztergom
Hungary	Investigator site	Gyula
Hungary	Investigator Site	Székesfehérvar
Hungary	Investigator Site	Szikszo
Hungary	Investigator Site	Szombathely
Hungary	Investigator Site	Veszprém
Mexico	Investigator Site	Culiacan
Mexico	Investigator Site	Leon
Mexico	Investigator Site 1	Mexico City
Mexico	Investigator Site 2	Mexico City
Mexico	Investigator Site	Mexico City 1
Mexico	Investigator Site 1	Monterrey
Mexico	Investigator Site 2	Monterrey
Moldova, Republic of	Investigator Site	Chisinau
Moldova, Republic of	Investigator Site	Chisinau
North Macedonia	Investigator Site 1	Skopje
North Macedonia	Investigator Site 2	Skopje
Poland	Investigator Site	Bydgoszcz
Poland	Investigator Site	Elblag
Poland	Investigator Site 2	Elblag
Poland	Investigator Site	Gdynia
Poland	Investigator Site	Grodzisk Mazowiecki
Poland	Investigator Site	Lublin
Poland	Investigator SIte	Poznan
Poland	Investigator Site	Sochaczew
Poland	Investigator Site	Torun
Poland	Investigator Site	Warszawa
Romania	Investigator Site	Bucharest
Romania	Investigator Site	Oradea
Romania	Investigator Site	Timisoara
Serbia	Investigator Site 1	Belgrade
Serbia	Investigator Site 2	Belgrade
Serbia	Investigator Site 3	Belgrade
Serbia	Investigator Site	Niska Banja
Spain	Investigator Site	Cordoba
Spain	Investigator Site	Madrid
Spain	Investigator Site	Santander
Spain	Investigator Site 2	Santander
Spain	Investigator Site 1	Santiago de Compostela
Spain	Investigator Site 2	Santiago de Compostela
United States	Investigator Site	Albuquerque	New Mexico
United States	Investigator Site	Birmingham	Alabama
United States	Investigator Site	Charleston	South Carolina
United States	Investigator Site	Hemet	California
United States	Investigator site	Hialeah	Florida
United States	Investigator Site	Homestead	Florida
United States	Investigator Site	La Palma	California
United States	Investigator site	Los Angeles	California
United States	Investigator Site	Los Angeles	California
United States	Investigator Site	Memphis	Tennessee
United States	Investigator Site	Mesquite	Texas
United States	Investigator Site	New York	New York
United States	Investigator Site	Orlando	Florida
United States	Investigator site	Overland Park	Kansas
United States	Investigator Site	Stockbridge	Georgia
United States	Investigator site	Ventura	California
United States	Investigator Site	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Ablynx

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Czechia,  Georgia,  Germany,  Hungary,  Mexico,  Moldova, Republic of,  North Macedonia,  Poland,  Romania,  Serbia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number and Percentage of Subjects With American College of Rheumatology 20 (ACR20) at 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	Number and Percentage of Subjects With ACR50 and ACR70 Response at 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
Secondary	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	DAS28(CRP) = (0.56 × vTJC28) + (0.28 × vSJC28) + (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
Secondary	Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Week 12	DAS28(ESR) = (0.56 × vTJC28) + (0.28 × vSJC28) + (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
Secondary	Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at 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
Secondary	Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at 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
Secondary	Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at 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
Secondary	Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Week 12	DAS28(ESR) = (0.56 × vTJC28) + (0.28 × vSJC28) + (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
Secondary	Number and Percentage of Subjects in Remission Using SDAI at 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
Secondary	Number and Percentage of Subjects in Remission Using CDAI at 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
Secondary	Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at 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
Secondary	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at 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
Secondary	Change From Baseline in Physical and Mental Component Scores of Short Form Health Survey (SF-36) at 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
Secondary	Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at 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
Secondary	Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R)	Values below the limit of quantification are imputed with the lower limit of quantification (LLOQ).	From baseline until Week 12
Secondary	Pharmacokinetics: ALX-0061 Concentration in Serum at Week 12		From baseline until Week 12
Secondary	Number and Percentage of Subjects With Development of a Treatment-emergent Antidrug Antibody Response		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)
Secondary	Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity		From baseline until Week 12
Secondary	Number of Treatment-emergent Adverse Event by Severity		From baseline until Week 12
Secondary	Number and Percentage of Subjects With a Treatment-related Treatment-emergent Adverse Event	treatment related = considered at least possibly related to study drug by the Investigator	From baseline until Week 12
Secondary	Number of Treatment-related Treatment-emergent Adverse Event	treatment related = considered at least possibly related to study drug by the Investigator	From baseline until Week 12