Natrunix in Combination With Methotrexate for Rheumatoid Arthritis Treatment

NCT06590090 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: PT067
• Study Type: interventional
• Target: 108
• Locations: 0 countries
• Sites: N/A

Brief Summary

Approximately 108 subjects will be randomized in 2 arms in 2:1 ratio to receive weekly subcutaneous injections of either 400mg Natrunix + MTX weekly or placebo + MTX weekly for 14 weeks. At the week 14 visit subjects in both arms will undergo a safety follow up visit OR begin receiving biweekly subcutaneous injections of 400mg Natrunix for 14 weeks as part of an Open Label Extension (OLE). The study will last for a maximum of 33 weeks, including: a screening period of up to 4 weeks, a 14-week double-blinded treatment phase followed by a 14-week open label extension phase and one-week follow-up.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• ACR 20 response

  The American College of Rheumatology (ACR) response criteria for rheumatoid arthritis (RA) are used to measure how effective study drug is in this study.

  at 14 weeks from baseline

Secondary Outcomes (34)

• ACR 50 response rate

  at 14 weeks from baseline

• Mean change in number of swollen and tender joints based on 66/68-joint count

  at 14 weeks from baseline

• Mean change in NRS-pain score

  at 14 weeks from baseline

• ACR 70 response rate

  at 2, 4, 8, 12 and 14 weeks from baseline

• ACR 20 response rate

  at 2, 4, 8 and 12 weeks from baseline

Study Arms (2)

400mg Natrunix + MTX weekly

EXPERIMENTAL

Subjects will receive 400mg Natrunix and MTX weekly

Biological: Natrunix 400 mg; Drug: Methotrexate (MTX)

Placebo+ MTX weekly

EXPERIMENTAL

Subjects will receive placebo and MTX weekly

Drug: Placebo; Drug: Methotrexate (MTX)

Interventions

Natrunix 400 mg BIOLOGICAL

The active ingredient of Natrunix is an IgG4 monoclonal antibody indistinguishable from that naturally occurring in an IL-1a-immune healthy human. Natrunix is formulated as 200 mg/mL sterile liquid in a stabilizing isotonic formulation buffered to pH 7.0. The product is filled into a 2 mL glass pre-filled syringe suitable for subcutaneous injection. The drug product is formulated and buffered to a neutral body pH of 7.0.

Also known as: methotrexate

400mg Natrunix + MTX weekly

Placebo DRUG

Placebo is a sterile liquid solution filled into a 2 mL glass pre-filled syringe, suitable for subcutaneous injection, containing the exact same buffer matrix used for Natrunix drug product

Placebo+ MTX weekly

Methotrexate (MTX) DRUG

Methotrexate may be administered in pill form by mouth, as liquid by mouth, or by subcutaneous injection.Subjects enrolled in this study should be receiving a stable minimum weekly dose of 10mg. Weekly methotrexate should not exceed 25 mg/week.

400mg Natrunix + MTX weekly; Placebo+ MTX weekly

Eligibility Criteria

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

You may qualify if:

• Weight \> 40 kg
• Diagnosis of moderate to severe RA according to 2010 ACR/EULAR classification criteria.
• Patients must be methotrexate-inadequate responders.
• a. Persistent moderate to severe RA disease activity (i.e., criteria #2 above) despite ongoing treatment with MTX.
• 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 (Erythrocyte Sedimentation Rate) \> 3.2.
• Subject must be receiving MTX treatment at a dosage of 10-25 mg/week for a minimum of 12 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.
• Subjects must have discontinued all csDMARDs (excluding MTX) for at least 4 weeks or 5 half-lives prior to enrollment, whichever is longer.
• Subjects taking regular NSAIDs, Acetaminophen, oral corticosteroids (\<10mg/day prednisone equivalent), and inhaled corticosteroids must be on a stable dose for 2 weeks prior to enrollment.
• Subjects must have discontinued high potency opioids (oxycodone, fentanyl, etc.) for at least 4 weeks prior to enrollment.
• 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.
• Patients must provide at least 7 consecutive days of NRS-pain data in the subject's 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.
• 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).
• 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.
• 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.
• 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.

You may not qualify if:

• History of treatment with Natrunix for any reason.
• Any active, chronic, or recurrent infections. (e.g., ongoing bacterial, viral, or fungal infection).
• Comorbid severe psychiatric illness and/or complicated social situations that would limit compliance with study requirements.
• 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.
• Patients who have failed more than 1 conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) regimen (excluding Methotrexate monotherapy) due to inefficacy at any point prior to enrollment.
• Patients who have received any biological therapy including anakinra, rilonacept, canakinumab, adalimumab, certolizumab, etanercept, golimumab, infliximab, abatacept, tocilizumab, sarilumab, and biosimilars at any point prior to enrollment.
• Treatment with JAK inhibitors at any point prior to enrollment.
• Patients who have received treatment with Injectable corticosteroids within 8 weeks prior to enrollment.
• 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.
• Pregnant or breastfeeding patients.
• Patients with current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within a year prior to enrollment.
• 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.
• Clinically significant laboratory abnormalities, including:
• Hemoglobin \<9.0 g/dL
• White blood cell counts \< 4000/mm3

Sponsors & Collaborators

• XBiotech, Inc.: lead

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Haritha Pallapotu

CONTACT

512-386-2992; hpallapotu@xbiotech.com

Norma Gonzalez

CONTACT

ngonzalez@xbiotech.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2024
• First Posted: September 19, 2024
• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): July 15, 2027
• Last Updated: December 9, 2025

Record last verified: 2025-12