Rheumatoid ArthritisPhase 2NCT05363891
Natrunix or Placebo in Combination With Methotrexate in Rheumatoid Arthritis
A Phase 2 study testing Natrunix in people with Rheumatoid Arthritis, run by XBiotech, Inc. at 26 sites in United States.
Trial summary
Phase II, Double-Blind, Placebo-Controlled, Randomized Trial Examining Natrunix in Combination with MTX (+Folate) for the Treatment of Rheumatoid Arthritis Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Natrunix
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 243 participants
- Where
- 26 sitesUnited States
- Study dates
- 8 Aug 2023to 31 Oct 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients may be included in the study if they meet all of the following criteria:
- Weight > 40 kg
- Diagnosis of moderate to severe RA according to 2010 ACR/EULAR classification criteria.
- Patients must be methotrexate-inadequate responders.
- Persistent moderate to severe RA disease activity (ie. 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 > 3.2.
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- 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.
- 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 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.
- 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.
Who cannot join
- Patients with ANY of the following will be excluded from the study:
- 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 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.
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- Treatment with JAK inhibitors within 4 weeks (or 5 half-lives, whichever is longer) prior to randomization.
- 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 Day 0.
- 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
- Absolute neutrophil count (ANC) <1500/mm3
- Platelet count <100,000/mm3
- Absolute lymphocyte count (ALC) <500/mm3
- eGFR <60 mL/min
- Alanine Aminotransferase (ALT) >1.5x lab upper limit of normal (ULN)
- Aspartate Aminotransferase (AST) >1.5x lab upper limit of normal (ULN)
- Bilirubin >1.5x lab upper limit of normal (ULN)
- 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.
- Major surgery (including joint surgery) within 3 months of baseline.
- Patients who have suffered severe trauma or fracture within 4 weeks of baseline.
- Evidence of active hepatitis B, hepatitis C, or HIV infection.
- Patients positive for HBsAg and/or positive for anti-HBc antibody (regardless of anti-HBs antibody status) are excluded.
- 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.
- 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:
- Coexisting diseases which are contraindicated for MTX treatment.
- 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.
- Concurrent autoimmune disease with the exception of Sjogren's syndrome secondary to rheumatoid arthritis.
Trial locations and contacts
26 sites in 1 country.
26 sites in 1 country
United States26 sites
HARAC Research Corp
Avon Park, Florida, 33825
Overlake Arthritis and Osteoporosis Center
Bellevue, Washington, 98004
ClinRx Research Joseph INC
Carrollton, Texas, 75007
Medvin Clinical Research
Covina, California, 91722
Altoona Center for Clinical Research
Duncansville, Pennsylvania, 16635
T. Joseph Raoof MD, INC
Encino, California, 91436
Reliable Clinical Research, LLC
Hialeah, Florida, 33112
Accurate Clinical Management LLC
Houston, Texas, 77089
Accurate Clinical Research Inc
Houston, Texas, 77089
Pioneer Research Solutions, INC
Houston, Texas, 77099
Accurate Clinical Research Inc
Lake Charles, Louisiana, 70605
Southwest Rheumatology Research, LLC
Mesquite, Texas, 75150
Angels Clinical Research Institute
Miami, Florida, 33122
D&H National Research Centers
Miami, Florida, 33155
BioMed Research & Medical Center, LLC
Miami, Florida, 33156
Advanced Clinical Research of Orlando
Ocoee, Florida, 34761
Greater Chicago Specialty Physicians, LLC
Orland Park, Illinois, 60467
Desert Medical Advances
Rancho Mirage, California, 92270
Epic Medical Research, LLC
Red Oak, Texas, 75115
Accurate Clinical Management, LLC
Richmond, Texas, 77469
Medvin Clinical Research
Riverside, California, 92518
Greater Chicago Specialty Physicians, LLC
Schaumburg, Illinois, 60195
DH Tamarac Research Center
Tamarac, Florida, 33321
DM Clinical Research
Tomball, Texas, 77375
Medvin Clinical Research
Tujunga, California, 91042
Inland Rheumatology Clinical Trials, Inc.
Upland, California, 91786
About this study
Official title: Phase II, Double-blind, Placebo-Controlled, Randomized Trial Examining Natrunix in Combination With Methotrexate (+Folate) for the Treatment of Rheumatoid Arthritis
Phase II, Double-Blind, Placebo-Controlled, Randomized Trial Examining Natrunix in Combination with MTX (+Folate) for the Treatment of Rheumatoid Arthritis
Read the detailed description
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
- Rheumatoid Arthritis
- Being tested
- Natrunix, Placebo
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NatrunixDrug
Also called True Human IgG4 monoclonal antibody
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.
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Natrunix 200mg with MTX(+Folate) | Experimental | Natrunix 200mg, subcutaneous injection in combination with Methotrexate (+Folate).This arm will enroll 70 subjects. Receives: Drug: Natrunix |
| Natrunix 400mg with MTX(+Folate) | Experimental | Natrunix 400mg, subcutaneous injection in combination with Methotrexate (+Folate).This arm will enroll 70 subjects. Receives: Drug: Natrunix |
| Placebo with MTX(+Folate) | Placebo comparator | Placebo in combination with Methotrexate (+Folate).This arm will enroll 70 subjects. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
ACR 20 response rate at 12 weeks.
The ACR is a measure used in clinical practice and clinical trial to assess medication efficacy in patients with RA, by notating improvements in swelling and tenderness in designated joints, as well as improvements in at least 3 out of 5 other categories. The other categories assessed are patient global assessment of disease activity, physician global assessment of disease activity, patient reported pain scale, disability/functionality questionnaire response, and acute phase reactant levels (CRP and ESR).
Measured: At 12 weeks from baseline
Secondary outcomes (2)
ACR 50 response rate at 12 weeks.
The ACR is a measure used in clinical practice and clinical trial to assess medication efficacy in patients with RA, by notating improvements in swelling and tenderness in designated joints, as well as improvements in at least 3 out of 5 other categories. The other categories assessed are patient global assessment of disease activity, physician global assessment of disease activity, patient reported pain scale, disability/functionality questionnaire response, and acute phase reactant levels (CRP and ESR).
Measured: At 12 weeks from baseline
Mean change in NRS-pain at 12 weeks
Numerical rating scale (NRS) is a validated measure used to assess chronic and acute pain using a 10-point rating scale. The rating for no pain is "0" and "worst possible pain" is 10.
Measured: At 12 weeks from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2022
- Study start8 Aug 2023
- Primary completion31 Oct 2024
- Study completion31 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Arm 1- Natrunix 200mg with MTX(+Folate) Arm 2 - Natrunix 400mg with MTX(+Folate) Arm 3- Placebo with MTX(+Folate)
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 243 participants (actual)
Sponsor and investigators
- Lead sponsor
- XBiotech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05363891
- Sponsor's protocol ID
- 2021-PT055
- Status last verified
- Jan 2025
- First submitted
- 2 May 2022
- Last updated
- 16 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II, Double-blind, Placebo-Controlled, Randomized Trial Examining Natrunix in Combination With Methotrexate (+Folate) for the Treatment of Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT05363891
- Acronym / sponsor ID
- 2021-PT055
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 243 participants (actual)
- Lead sponsor
- XBiotech, Inc.Industry (pharma, biotech, devices)
- Study start
- 8 Aug 2023 (actual)
- Primary completion
- 31 Oct 2024 (actual)
- Study completion
- 31 Oct 2024 (actual)
- First posted
- 6 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase II, Double-Blind, Placebo-Controlled, Randomized Trial Examining Natrunix in Combination with MTX (+Folate) for the Treatment of Rheumatoid Arthritis
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Arm 1- Natrunix 200mg with MTX(+Folate) Arm 2 - Natrunix 400mg with MTX(+Folate) Arm 3- Placebo with MTX(+Folate)
| Arm | Type | Receives |
|---|---|---|
| Natrunix 200mg with MTX(+Folate) | Experimental | Drug: NatrunixNatrunix 200mg, subcutaneous injection in combination with Methotrexate (+Folate).This arm will enroll 70 subjects. |
| Natrunix 400mg with MTX(+Folate) | Experimental | Drug: NatrunixNatrunix 400mg, subcutaneous injection in combination with Methotrexate (+Folate).This arm will enroll 70 subjects. |
| Placebo with MTX(+Folate) | Placebo comparator | Drug: PlaceboPlacebo in combination with Methotrexate (+Folate).This arm will enroll 70 subjects. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Weight > 40 kg
- Diagnosis of moderate to severe RA according to 2010 ACR/EULAR classification criteria.
- Patients must be methotrexate-inadequate responders.
- 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.
- 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.
Key exclusion criteria (31 listed)
- 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 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NatrunixAlso: True Human IgG4 monoclonal antibodyNatrunix 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. | Drug | Natrunix 200mg with MTX(+Folate), Natrunix 400mg with MTX(+Folate) |
| PlaceboPlacebo | Drug | Placebo with MTX(+Folate) |
Primary outcome
ACR 20 response rate at 12 weeks.
Time frame: At 12 weeks from baseline
The ACR is a measure used in clinical practice and clinical trial to assess medication efficacy in patients with RA, by notating improvements in swelling and tenderness in designated joints, as well as improvements in at least 3 out of 5 other categories. The other categories assessed are patient global assessment of disease activity, physician global assessment of disease activity, patient reported pain scale, disability/functionality questionnaire response, and acute phase reactant levels (CRP and ESR).
2 secondary outcomes
ACR 50 response rate at 12 weeks.
Time frame: At 12 weeks from baseline
Mean change in NRS-pain at 12 weeks
Time frame: At 12 weeks from baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
26 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Natrunix in people with Rheumatoid Arthritis, run by XBiotech, Inc. at 26 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ACR 20 response rate at 12 weeks. (time frame: At 12 weeks from baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2025.