Natrunix or Placebo in Combination With Methotrexate in Rheumatoid Arthritis

NCT ID: NCT05363891

Last Updated: 2025-01-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

243 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-08-08

Study Completion Date

2024-10-31

Brief Summary

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Phase II, Double-Blind, Placebo-Controlled, Randomized Trial Examining Natrunix in Combination with MTX (+Folate) for the Treatment of Rheumatoid Arthritis

Detailed Description

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Potential subjects will be consented and screened for study eligibility and the enrolled will be randomized in a 1:1:1 ratio to receive either: 200 mg Natrunix; 400mg Natrunix; or placebo. All subjects will enter the study on stable MTX dose. Subjects will receive once weekly injection of Natrunix or placebo in addition to MTX for 12 weeks. The study will conclude after 13 weeks.

Study Duration is 17 weeks (4-week maximum screening + 12-week treatment period = 1-week follow-up.

The primary objective is to determine the ACR 20 response rate in subjects receiving stable dose of MTX and after 12 weeks of treatment with either Natrunix or placebo. The study will also examine what impact the addition of Natrunix or placebo has on the scores of various rheumatological grading scales, including ACR 50, NRS-pain score, and 66/68-joint count, as well as safety. All subjects enrolled in the study will be taking concomitant methotrexate.

Conditions

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Rheumatoid Arthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Arm 1- Natrunix 200mg with MTX(+Folate) Arm 2 - Natrunix 400mg with MTX(+Folate) Arm 3- Placebo with MTX(+Folate)
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Double-blind study

Study Groups

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Natrunix 200mg with MTX(+Folate)

Natrunix 200mg, subcutaneous injection in combination with Methotrexate (+Folate).This arm will enroll 70 subjects.

Group Type EXPERIMENTAL

Natrunix

Intervention Type DRUG

Natrunix is a unique kind of drug-an immunoglobulin cloned from a naturally occurring immune response from a healthy human donor. Natrunix blocks inflammation in a unique way-it is the only therapeutic that exclusively neutralizes interleukin-1α (IL-1α), a crucial mediator of interleukin-1 inflammation. Targeting IL-1α directly using a natural human monoclonal antibody may provide a safer and more effective means of blocking interleukin-1 in rheumatoid arthritis.

Natrunix 400mg with MTX(+Folate)

Natrunix 400mg, subcutaneous injection in combination with Methotrexate (+Folate).This arm will enroll 70 subjects.

Group Type EXPERIMENTAL

Natrunix

Intervention Type DRUG

Natrunix is a unique kind of drug-an immunoglobulin cloned from a naturally occurring immune response from a healthy human donor. Natrunix blocks inflammation in a unique way-it is the only therapeutic that exclusively neutralizes interleukin-1α (IL-1α), a crucial mediator of interleukin-1 inflammation. Targeting IL-1α directly using a natural human monoclonal antibody may provide a safer and more effective means of blocking interleukin-1 in rheumatoid arthritis.

Placebo with MTX(+Folate)

Placebo in combination with Methotrexate (+Folate).This arm will enroll 70 subjects.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo

Interventions

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Natrunix

Natrunix is a unique kind of drug-an immunoglobulin cloned from a naturally occurring immune response from a healthy human donor. Natrunix blocks inflammation in a unique way-it is the only therapeutic that exclusively neutralizes interleukin-1α (IL-1α), a crucial mediator of interleukin-1 inflammation. Targeting IL-1α directly using a natural human monoclonal antibody may provide a safer and more effective means of blocking interleukin-1 in rheumatoid arthritis.

Intervention Type DRUG

Placebo

Placebo

Intervention Type DRUG

Other Intervention Names

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True Human IgG4 monoclonal antibody

Eligibility Criteria

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Inclusion Criteria

Patients may be included in the study if they meet all of the following criteria:

1. Weight \> 40 kg
2. Diagnosis of moderate to severe RA according to 2010 ACR/EULAR classification criteria.
3. Patients must be methotrexate-inadequate responders.

a. Persistent moderate to severe RA disease activity (ie. criteria #2 above) despite ongoing treatment with MTX.
4. Meets the following minimum disease activity criteria at screening: ≥6 swollen joints (based on DAS28) and ≥6 tender joints (based on DAS28) and DAS-ESR \> 3.2.
5. Subject must be receiving MTX treatment at a dosage of 15-25 mg/week for a minimum of12 weeks; and be receiving a stable dose of MTX for \>4 weeks preceding randomization.

Subjects must also be in principle agreement to remain at the pre-randomization stable dose of MTX for the entire duration of the study. Subjects must also be willing to take a minimum of 5 mg folic acid/folinic acid per week for the duration of the study.
6. Male or female, at least 18 years of age, willing to provide informed consent, able to attend all clinic visits,comply with study-related procedures and able to understand and complete study-related questionnaires.
7. Patients must provide at least 7 consecutive days of NRS-pain data in the subjects diary prior to the baseline visit. The NRS pain diary should ideally be completed for the 7 days immediately prior to Visit 1 (when the first dose of test drug is administered). Subjects may record more than 7 days of pain records in the diary for their baseline. At least seven consecutive days of pain diary are necessary to be eligible for enrollment in the study.
8. Peripheral blood CD19+ cell count recovery to \>10 cells/uL or \>1% of total lymphocyte count (Required only for subjects who have received a Rituximab (or anti-CD20 biosimilar) infusion within 12 months prior to enrollment).
9. Female patients of childbearing potential must consent to undergo a serum pregnancy test at enrollment, and urine pregnancy tests at each visit after screening. Women of non-childbearing potential include those considered to have a medical history that indicates that pregnancy is not a reasonable risk, including post-menopausal women and those with a history of hysterectomy or surgically sterilized.
10. In case of female patients of childbearing potential, willingness to use one method of contraception of high efficacy during the entire study period. These methods can include but not limited to hormonal contraceptives, intrauterine devices, condoms, diaphragms, etc.
11. Males participating in this clinical research study should not get a sexual partner pregnant during their participation in this research study as the effect of the study drug on sperm is not known. Male contraception methods can include but are not limited to mechanical methods (e.g., abstinence, non-vaginal intercourse), contemporary methods comprising barrier methods (e.g., spermicide, condom, sponge, diaphragm and cervical cap) and vasectomy.

Exclusion Criteria

Patients with ANY of the following will be excluded from the study:

1. History of treatment with Natrunix for any reason.
2. Any active, chronic, or recurrent infections. (e.g., ongoing bacterial, viral, or fungal infection).
3. Comorbid severe psychiatric illness and/or complicated social situations that would limit compliance with study requirements.
4. Patients with a positive result of TB test (QuantiFERON-TB Gold (QFT) at screening unless the patients can present a documentation of completion of TB treatment course by the local Health Department and a clear chest x-ray at enrollment.
5. Patients must not have received any biological therapy including anakinra, rilonacept, canakinumab, adalimumab, certolizumab, etanercept, golimumab, infliximab, abatacept, tocilizumab, sarilumab, and biosimilars within 8 weeks prior to randomization.
6. Treatment with JAK inhibitors within 4 weeks (or 5 half-lives, whichever is longer) prior to randomization.
7. Investigational therapy administered within a time interval less than at least 5 half-lives of the investigational agent prior to the first scheduled day of dosing in this study.
8. Pregnant or breastfeeding patients.
9. Patients with current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within a year prior to Day 0.
10. Uncontrolled heart disease, including NYHA Class III or IV congestive heart failure, ventricular arrhythmia, uncontrolled blood pressure (defined as ≥ 160/100 mm Hg), or unstable angina.
11. Clinically significant laboratory abnormalities, including:

1. Hemoglobin \<9.0 g/dL
2. White blood cell counts \< 4000/mm3
3. Absolute neutrophil count (ANC) \<1500/mm3
4. Platelet count \<100,000/mm3
5. Absolute lymphocyte count (ALC) \<500/mm3
6. eGFR \<60 mL/min
7. Alanine Aminotransferase (ALT) \>1.5x lab upper limit of normal (ULN)
8. Aspartate Aminotransferase (AST) \>1.5x lab upper limit of normal (ULN)
9. Bilirubin \>1.5x lab upper limit of normal (ULN)
10. GGT: Natrunix does not put any load on the liver. GGT levels are not assessed to determine potential risk of hepatoxicity. Rather GGT levels are used as an additional screening measure to assess for occult hepatobiliary disease that may be missed with more common liver enzyme assays given the requirement for concurrent treatment with therapeutic methotrexate throughout the study. Small excursions from normal values are acceptable based on Physician/Sponsor judgment.
12. Major surgery (including joint surgery) within 3 months of baseline.
13. Patients who have suffered severe trauma or fracture within 4 weeks of baseline.
14. Evidence of active hepatitis B, hepatitis C, or HIV infection.

1. Patients positive for HBsAg and/or positive for anti-HBc antibody (regardless of anti-HBs antibody status) are excluded.
2. Patients who are positive for Hepatitis C antibody and negative when the Hepatitis C RNA-PCR assay is performed on a subsequent sample will be eligible to participate. Patients who are positive for Hepatitis C antibody and have a positive result for the HCV when the Hepatitis C RNA-PCR assay is performed on the subsequent sample will not be eligible to participate.
15. Any other concomitant disease, disorder, or condition that could interfere with the interpretation of study endpoints, or the patient's ability to participate in and complete the study., including but not limited to:

1. Coexisting diseases which are contraindicated for MTX treatment.
2. Cardiovascular, renal, pulmonary, gastrointestinal, or nervous system disorders that, in the opinion of the principal investigator and/or study medical monitor, make the patient not suitable for enrollment.
3. Concurrent autoimmune disease with the exception of Sjogren's syndrome secondary to rheumatoid arthritis.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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XBiotech, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Medvin Clinical Research

Covina, California, United States

Site Status

T. Joseph Raoof MD, INC

Encino, California, United States

Site Status

Desert Medical Advances

Rancho Mirage, California, United States

Site Status

Medvin Clinical Research

Riverside, California, United States

Site Status

Medvin Clinical Research

Tujunga, California, United States

Site Status

Inland Rheumatology Clinical Trials, Inc.

Upland, California, United States

Site Status

HARAC Research Corp

Avon Park, Florida, United States

Site Status

Reliable Clinical Research, LLC

Hialeah, Florida, United States

Site Status

Angels Clinical Research Institute

Miami, Florida, United States

Site Status

D&H National Research Centers

Miami, Florida, United States

Site Status

BioMed Research & Medical Center, LLC

Miami, Florida, United States

Site Status

Advanced Clinical Research of Orlando

Ocoee, Florida, United States

Site Status

DH Tamarac Research Center

Tamarac, Florida, United States

Site Status

Greater Chicago Specialty Physicians, LLC

Orland Park, Illinois, United States

Site Status

Greater Chicago Specialty Physicians, LLC

Schaumburg, Illinois, United States

Site Status

Accurate Clinical Research Inc

Lake Charles, Louisiana, United States

Site Status

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

Site Status

ClinRx Research Joseph INC

Carrollton, Texas, United States

Site Status

Accurate Clinical Management LLC

Houston, Texas, United States

Site Status

Accurate Clinical Research Inc

Houston, Texas, United States

Site Status

Pioneer Research Solutions, INC

Houston, Texas, United States

Site Status

Southwest Rheumatology Research, LLC

Mesquite, Texas, United States

Site Status

Epic Medical Research, LLC

Red Oak, Texas, United States

Site Status

Accurate Clinical Management, LLC

Richmond, Texas, United States

Site Status

DM Clinical Research

Tomball, Texas, United States

Site Status

Overlake Arthritis and Osteoporosis Center

Bellevue, Washington, United States

Site Status

Countries

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United States

Other Identifiers

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2021-PT055

Identifier Type: -

Identifier Source: org_study_id

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