## Protocol Section
### Identification Module
**NCT ID:** NCT02364479

**Brief Title:** Treatment of Axial Spondyloarthritis by Recombinant Human Tumor Necrosis Factor-α Receptor Ⅱ IgG Fc Fusion Protein

**Official Title:** Treatment of Active Axial Spondyloarthritis by Recombinant Human Tumor Necrosis Factor-α Receptor Ⅱ IgG Fc Fusion Protein Injection: a Randomized, Double-blind, Multicentral Clinical Trial to Investigate the Efficacy and Safety of Yisaipu®

#### Organization Study ID Info
**ID:** [2013]2-21
#### Organization
**Class:** OTHER
**Full Name:** Sun Yat-sen University
### Status Module
#### Completion Date
**Date:** 2016-08-28

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2019-12-19

**Type:** ACTUAL

**Last Update Submit Date:** 2019-12-17

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2016-07-28

**Type:** ACTUAL

#### Start Date
**Date:** 2014-02-10

**Type:** ACTUAL

**Status Verified Date:** 2019-12

#### Study First Post Date
**Date:** 2015-02-18
**Type:** ESTIMATED
**Study First Submit Date:** 2015-02-10
**Study First Submit QC Date:** 2015-02-10
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Sun Yat-sen University

#### Responsible Party

**Investigator Affiliation:** Sun Yat-sen University

**Investigator Full Name:** Gu Jieruo

**Investigator Title:** Division of Rheumatology of Third Affiliated Hospital of Sun Yat-sen University

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** This is a randomized, double-blind, multicentral clinical trial to investigate the efficacy and safety of Recombinant Human Tumor Necrosis Factor-α Receptor Ⅱ IgG Fc fusion protein injection (Yisaipu®) in the treatment of active axial spondyloarthritis(SpA). The primary purpose is to assess the different situations in maintaining treatment programme in SpA patients with controlled inflammation by Yisaipu®. And the second purpose is to assess the eficacy and safety of Yisaipu® in axial SpAs. The trial will include 150 patients with stable NSAIDs therapy, and at the first stage they will receive 24-week full-dose of Yisaipu®. Then at the second stage the patients who achieve low disease activity (LDA, ASDAS\<2.1) at 24th week will be randomizedly divided into three group: full-dose of Yisaipu® group, half-dose of Yisaipu® group and placebo group. And the blind stage will last for 48 weeks. Patients who complete the 72-week therapy or achieve disease-flare criteria during the blind stage would finish the study.

**Detailed Description:** This randomised controlled trial enrolled adult patients aged 18 years or older diagnosed with non-radiographic axial spondyloarthritis at 3 centres in China. Patients had to fulfil ASAS axial spondyloarthritis criteria but could not fulfil the modified New York radiologic criterion for ankylosing spondylitis,and had to have objective evidence of active inflammation or chronic structral change，such as bone erosion or fat metaplasia in the sacroiliac joints on MRI at screening. Active disease activity was defined as a disease activity score in ASDAS-CRP ≥2.1,or Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\] ≥4 on a numerical rating scale of 0-10, and an inadequate response to more than one non-steroidal anti-inflammatory drugs (NSAIDs) for 4 weeks at least, intolerance to NSAIDs, or contraindication for NSAIDs. No change in NSAIDs dose was required from 2 weeks before screening to the end of the study. Dose stability or discontinuation was required for 4 weeks before baseline for concomitant DMARDs or corticosteroids (prednisone or equivalent at a dose of less than 10 mg/day). Chinese herbal medicine, physical therapy, or live (attenuated) vaccine, or intravenous immunoglobulin IgG, was required for discontinuation and wash period for at least 4 weeks. Patients were excluded if they had previously taken or were taking biologic treatment, any biologic Dmards such as IL-6 or CD-20 inhibitors. Patients with latent tuberculosis infection were included only when local guidelines were followed for prophylactic treatment and if treatment was initiated before Yisaipu.

All patients provided written informed consent, and the study protocol was approved by an institutional review board or independent ethics committee at each study site. The study was conducted in accordance with applicable regulations and the ethical principles of Good Clinical Practice as defined by the International Conference on Harmonisation (ICH) and the Declaration of Helsinki.

A randomized envelope was used to enrol all patients at the baseline visit and to randomly assign qualifying patients in a 1:1:1 ratio to receive either blinded Yisaipu 50 mg subcutaneously every week or 25 mg subcutaneously every week or matching placebo at week 24. All study personnel, including the sponsor (with the exception of the Sanshengguojian drug supply management team), investigator, and study site personnel, and the patient remained blinded to treatment throughout the double-blinded period from week 24 through week 72 of the study. Investigational products were provided to maintain blinding.

In the initial open-label period, enrolled patients were given subcutaneous injections of 50 mg Yisaipu every week for 36 weeks. Participants were given the dose of NSAIDs they had been receiving at screening; a dose decrease or discontinuation was allowed when the patients were intolerance to NSAIDs, or contraindication for NSAIDs. Patients who achieved clinical remission, defined as achieving ASDAS inactive or moderate disease (ASDAS score \<2.1) at weeks 24, were randomly assigned to receive either blinded 50mg Yisaipu (continuation arm), 25mg Yisaipu(reduction arm) or matching placebo (withdrawal arm) for 48 weeks during the double-blind period, for a total of 72 weeks of treatment.

During the double-blind period, patients who experienced a flare (defined as an increase in BASDAI ≥2 points compare to the BASDAI score when randomization) were allocate to termination of this trial.

### Conditions Module

**Conditions:**

- Spondyloarthritis

**Keywords:**

- relapse

- Yisaipu

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 150

**Type:** ACTUAL

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Recombinant Human Tumor Necrosis Factor-α Receptor Ⅱ IgG Fc Fusion Protein Injection, 50mg per week, Subcutaneous injection

**Intervention Names:**

- Drug: 50mg Yisaipu

**Label:** 50mg etanercept

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Recombinant Human Tumor Necrosis Factor-α Receptor Ⅱ IgG Fc Fusion Protein Injectio, 25mg per week, Subcutaneous injection

**Intervention Names:**

- Drug: 25mg etanercept

**Label:** 25mg etanercept

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** Placebo, Subcutaneous injection per week

**Intervention Names:**

- Drug: Placebo

**Label:** Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- 50mg etanercept

**Description:** Recombinant Human Tumor Necrosis Factor-α Receptor Ⅱ IgG Fc Fusion Protein Injection, 50mg per week

**Name:** 50mg Yisaipu

**Other Names:**

- 50mg entanercept(Yisaipu)

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- 25mg etanercept

**Description:** Recombinant Human Tumor Necrosis Factor-α Receptor Ⅱ IgG Fc Fusion Protein Injection, 25mg per week

**Name:** 25mg etanercept

**Other Names:**

- 25mg entanercept(Yisaipu)

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Placebo

**Description:** The injection method and frequency of placebo is the same as the other arms.

**Name:** Placebo

**Other Names:**

- placebo arm

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period

**Measure:** proportion of patients achieving ASDAS<2.1

**Time Frame:** 72 week

#### Secondary Outcomes

**Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period

**Measure:** proportion of patients achieving ASDAS<1.3

**Time Frame:** 72 weeks

**Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period

**Measure:** proportion of ASDAS major improvement

**Time Frame:** 72 weeks

**Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period

**Measure:** proportion of ASDAS clinically important improvement

**Time Frame:** 72 weeks

**Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period

**Measure:** ASAS 20

**Time Frame:** 72 weeks

**Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period

**Measure:** ASAS 40

**Time Frame:** 72 weeks

**Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period

**Measure:** ASAS5/6

**Time Frame:** 72 weeks

**Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period

**Measure:** ASAS PR

**Time Frame:** 72 weeks

**Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period

**Measure:** BASDAI50

**Time Frame:** 72 weeks

**Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period

**Measure:** BASDAI

**Time Frame:** 72 weeks

**Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period

**Measure:** BASFI

**Time Frame:** 72 weeks

**Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period

**Measure:** BASMI

**Time Frame:** 72 weeks

**Description:** The unabbreviated scale title is VAS from 0 to 100mm. 100 mm mean the most severe pain

**Measure:** spinal pain score

**Time Frame:** 72 weeks

**Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period

**Measure:** patient global assessment(PGA) score

**Time Frame:** 72 weeks

**Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period

**Measure:** physician global assessment(PhGA) score

**Time Frame:** 72 weeks

**Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period

**Measure:** ESR

**Time Frame:** 72 weeks

**Description:** in the groups given 50 mg Yisaipu, 25mg Yisaipu compared to placebo in the double-blind period

**Measure:** CRP

**Time Frame:** 72 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Fulfill the 2009 ASAS criteria for axial spondyloarthritis(SpA), and without bilateral more than grave 2 or unilateral more than grave 3 sacroilitis on X ray plan
* Active disease phase of SpA, defined as BASDAI≥4 or ASDAS≥2.1
* Inadequate response to NSAID≥4 week
* Application of NSAID with stable dose for no less than 2 weeks
* Stable dose of prenisone for at least four weeks at ≤10mg per day if used at screening, or stop use for at least 4 weeks.
* Stable dose of any DMARD for at least four weeks if used at screening, or stop use for at least 4 weeks
* Stop and receiving washing out for at least 4 week if receiving Chinese traditional drug for AS, physical treatment, vaccication or IVIG.
* The lab exam should achieve the criteria as below: Hb≥85g/L, 3.5×109/L≤WBC count≤10×109/L, PLT≥ lower limit of normal range, ALT≤2 fold of upper limit of normal range, serum creatine ≤upper limit of normal range.
* Negative pregnacy test for female patients. And promise to carry out contraception during the trial and 6 weeks after the trial is ended.
* Sign the informed consent.

Exclusion criteria:

* Previous application of any biologic agents.
* Allergic to any element of Yisaipu®
* Intolerance to NASID.
* History of active tubercolosis, or radiographic evidence of present or previous history of pulmonary tubercolosis, or close contact with patients with tubercolosis, or with high risk of infection of tubercolosis such as immune suppression status, or strong positive of PPD skin test with diameter ≥10mm.
* Presence of acute infection or acute onset of chronic infection at screen.
* Invasive fungal infection or conditional infection within 6 months prior to screen.
* Present or history of serious liver disease.
* History of infection on artifitial joints.
* Organ transplantation surgery within 6 months prior to screen.
* Presence of other autoimmune diseases, including IBD, psoriasis, uveitis, SLE, multiple sclerosis, etc.
* History of congestive heart failure.
* History of malignancies within 5 years prior to screen, excluding complete resection of squamous cell carcinoma, or basal cell carcinoma or cervical carcinoma in situ.
* AIDS or HIV infection.
* History of lymphoma or lymphoproliferative disorders.
* Presence of serious disorder of important organs or system.
* Presence of factors which may influence the compliance.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Guangzhou

**Country:** China

**Facility:** Department of Rheumatology, the Third Affiliated Hospital of Sun Yat-sen University

**State:** Guangdong

**Zip:** 510060

#### Overall Officials

**Official 1:**

**Affiliation:** 3rd Affiliated Hospital of Sun Yat-sen University

**Name:** Jieruo Gu, Professor

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000010335

- Term: Pathologic Processes

- ID: D000001850

- Term: Bone Diseases, Infectious

- ID: D000007239

- Term: Infections

- ID: D000001847

- Term: Bone Diseases

- ID: D000009140

- Term: Musculoskeletal Diseases

- ID: D000013122

- Term: Spinal Diseases

- ID: D000001168

- Term: Arthritis

- ID: D000007592

- Term: Joint Diseases

- ID: D000025242

- Term: Spondylarthropathies

- ID: D000000844

- Term: Ankylosis

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: BC05

- Name: Musculoskeletal Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M15961

- Name: Spondylitis

- Relevance: HIGH

- As Found: Spondyloarthritis

- ID: M23035

- Name: Spondylarthritis

- Relevance: HIGH

- As Found: Spondyloarthritis

- ID: M12284

- Name: Necrosis

- Relevance: HIGH

- As Found: Necrosis

- ID: M2697

- Name: Axial Spondyloarthritis

- Relevance: HIGH

- As Found: Axial Spondyloarthritis

- ID: M10283

- Name: Infections

- Relevance: LOW

- As Found: Unknown

- ID: M6368

- Name: Communicable Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5126

- Name: Bone Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5129

- Name: Bone Diseases, Infectious

- Relevance: LOW

- As Found: Unknown

- ID: M12097

- Name: Musculoskeletal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15919

- Name: Spinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M4476

- Name: Arthritis

- Relevance: LOW

- As Found: Unknown

- ID: M10621

- Name: Joint Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M23036

- Name: Spondylarthropathies

- Relevance: LOW

- As Found: Unknown

- ID: M4170

- Name: Ankylosis

- Relevance: LOW

- As Found: Unknown

- ID: T5412

- Name: Spondylarthropathy

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000013166

- Term: Spondylitis

- ID: D000025241

- Term: Spondylarthritis

- ID: D000089183

- Term: Axial Spondyloarthritis

- ID: D000009336

- Term: Necrosis

### Intervention Browse Module - Ancestors

- ID: D000000894

- Term: Anti-Inflammatory Agents, Non-Steroidal

- ID: D000018712

- Term: Analgesics, Non-Narcotic

- ID: D000000700

- Term: Analgesics

- ID: D000018689

- Term: Sensory System Agents

- ID: D000018373

- Term: Peripheral Nervous System Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000000893

- Term: Anti-Inflammatory Agents

- ID: D000018501

- Term: Antirheumatic Agents

- ID: D000005765

- Term: Gastrointestinal Agents

- ID: D000007166

- Term: Immunosuppressive Agents

- ID: D000007155

- Term: Immunologic Factors

### Intervention Browse Module - Browse Branches

- Abbrev: Infl

- Name: Anti-Inflammatory Agents

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: Analg

- Name: Analgesics

- Abbrev: Gast

- Name: Gastrointestinal Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M311

- Name: Etanercept

- Relevance: HIGH

- As Found: Activation

- ID: M4217

- Name: Anti-Inflammatory Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4218

- Name: Anti-Inflammatory Agents, Non-Steroidal

- Relevance: LOW

- As Found: Unknown

- ID: M4032

- Name: Analgesics

- Relevance: LOW

- As Found: Unknown

- ID: M20786

- Name: Analgesics, Non-Narcotic

- Relevance: LOW

- As Found: Unknown

- ID: M20604

- Name: Antirheumatic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M8881

- Name: Gastrointestinal Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10212

- Name: Immunosuppressive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000068800

- Term: Etanercept

### Misc Info Module

- Version Holder: 2024-05-24
