Rheumatoid Arthritis RAPhase 1/2NCT03410056
Safety and Efficacy of Efavaleukin Alfa in Subjects With Active Rheumatoid Arthritis
A Phase 1/2 study testing Efavaleukin alfa in people with Rheumatoid Arthritis RA, run by Amgen at 15 sites in 5 countries.
Trial summary
Phase 1b. To evaluate the safety and tolerability of subcutaneous (SC) dose administrations of Efavaleukin alfa in subjects with active rheumatoid arthritis (RA). Phase 2a. To evaluate the efficacy of Efavaleukin alfa at week 12 as measured by the American College of Rheumatology 20 percent improvement criteria (ACR… Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Rheumatoid Arthritis RA
- What is being tested?
- Efavaleukin alfa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 15 sitesin 5 countries
- Study dates
- 22 May 2018to 13 May 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subject has provided informed consent prior to initiation of any study specific activities/procedures.
- Age ≥ 18 to ≤ 70 years of age at screening.
- A diagnosis of RA consistent with the 1987 or 2010 American College of Rheumatology (ACR)/European League Against Rheumatism classification criteria.
- Active RA defined as: Phase 1b: DAS-28-CRP > 2.6 at screening. The 28-joint count consists of the finger joints excluding the distal interphalangeal joints, the wrists, elbows, shoulders, and knees. Phase 2a: ≥ 6 swollen joints (based on 66-joint count) and ≥ 6 tender joints (based on 68-joint count) at screening and baseline. The distal interphalangeal joint should be evaluated but not included in the total count to determine eligibility. Additionally, C-reactive protein (CRP) must be greater than the upper limit of normal (ULN) per the central laboratory at screening.
- Receiving treatment with methotrexate for ≥ 12 weeks and on a stable dose ≥ 15 mg weekly for ≥ 8 weeks prior to day 1. A lower methotrexate dose is acceptable (but no lower than 10 mg weekly) if it is the highest tolerated dose and gastrointestinal or hematologic toxicity at doses ≥ 15 mg weekly is documented by the investigator.
- Receiving treatment with folic or folinic acid per investigator judgment or according to local standard of care.
Show all 10Show fewer
- Phase 1b only: Subject may be receiving a stable dose of leflunomide, sulfasalazine, hydroxychloroquine, minocycline in combination with methotrexate and the dose must be stable for ≥ 8 weeks prior to day 1.
- Subject may be receiving a stable dose of prednisone ≤ 10mg daily or other equivalent corticosteroid dose and the dose must be stable for ≥ 2 weeks prior today 1.
- Phase 1b only. Normal or clinically acceptable electrocardiogram (ECG) values (12-lead reporting ventricular rate and PR, QRS, QT and QTc interval) at screening and baseline based on opinion of the investigator.
- Immunizations (tetanus, diphtheria, pertussis, seasonal influenza [during flu season], and pneumococcal [polysaccharide] vaccinations) up to date per local standards as determined by the investigator.
Who cannot join
- Class IV RA according to ACR revised response criteria
- Diagnosis of Felty's Syndrome (RA, splenomegaly and granulocytopenia).
- Prosthetic joint infection within 3 years of screening or native joint infection within 1 year prior to screening.
- Active infection (including chronic or localized infections) for which anti-infectives were indicated within 4 weeks prior to day 1 OR presence of serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to day 1.
- Known history of active tuberculosis.
- Positive test for tuberculosis during screening defined as either: positive purified protein derivative (PPD) (≥ 5 mm of induration at 48 to 72 hours after test is placed) OR positive Quantiferon test: a positive PPD and a history of Bacillus Calmette-Guérin vaccination are allowed with a negative Quantiferon test and negative chest x ray; a positive PPD test (without a history of Bacillus Calmette-Guérin vaccination) or a positive or indeterminate Quantiferon test are allowed if they have ALL of the following at screening: no symptoms per tuberculosis or sheet provided by Amgen; document history of a completed course of adequate prophylaxis(completed treatment for latent tuberculosis per local standard of care prior to the start of investigational product); no known exposure to a case of active tuberculosis after most recent prophylaxis; negative chest X-ray.
Show all 57Show fewer
- Positive for hepatitis B surface antigen, hepatitis B core antibody (confirmed by hepatitis B deoxyribonucleic acid (DNA) polymerase chain reaction [PCR] test) or detectable hepatitis C virus ribonucleic acid (RNA) by PCR (screening is generally done by hepatitis C antibody [HepCAb], followed by hepatitis C virus RNA by PCR if HepCAb is positive). A history of hepatitis B vaccination without history of hepatitis B is allowed.
- Phase 1b only: Positive for Human Immunodeficiency Virus (HIV) at screening or known to be HIV positive. Phase 2a only: Known history of HIV
- Phase 1b only: Positive drug or alcohol urine test for illicit drugs at screening. Prescription medications detected by the drug test are allowed if they are being taken under the direction of a physician.
- Presence of one or more significant concurrent medical conditions per investigator judgment, including but not limited to the following: poorly controlled diabetes or hypertension; chronic kidney disease stage IIIb, IV, or V; symptomatic heart failure (New York Heart Association class II, III, or IV); myocardial infarction or unstable angina pectoris within the past 12 months prior to randomization; severe chronic pulmonary disease (eg, requiring oxygen therapy); multiple sclerosis or any other demyelinating disease; major chronic inflammatory disease or connective tissue disease other than RA (eg, systemic lupus erythematosus with the exception of secondary Sjögren's syndrome).
- Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years.
- History of alcohol or substance abuse within 6 months of screening
- Phase 1b only: Current smoker, and/or use of any nicotine or tobacco containing products within the last 6 months prior to day 1. These types of products include but are not limited to: snuff, chewing tobacco, cigars, electronic cigarettes, cigarettes, pipes, or nicotine patches.
- Phase 1b only: Subject unwilling to limit alcohol consumption to ≤ 1 drink of alcohol per day and ≤ 3 drinks per week for the duration of the study, where a drink is equivalent to 12 ounces of regular beer, 8 to 9 ounces of malt liquor, 5 ounces of wine, or 1.5 ounces of 80 proof distilled spirits. Phase 1b only: Unwilling or unable to abstain from alcohol consumption within 48 hours prior to each visit (including screening).
- Subjects who have received intra-articular or systemic corticosteroid injections for treatment of acute RA flare (not being part of a regular therapeutic regimen) within 4 weeks prior to screening.
- Currently receiving or had treatment with cyclophosphamide, chlorambucil, nitrogen mustard, or any other alkylating agent ≤ 6 months prior to day 1.
- Prior treatment with more than a total of 3 therapies that include biologic disease modifying anti-rheumatic drug (DMARDs) or oral synthetic DMARDs (such as tofacinitib, baricitinib). Prior treatment consists of at least 4 doses of a given therapy where the doses were given solely for treatment of RA disease. Prior therapies must not have been used within the following time periods:
- ≤ 4 weeks prior to day 1 for etanercept and anakinra
- ≤ 6 months for rituximab
- ≤ 2 weeks for oral janus kinase inhibitors
- ≤ 9 weeks prior to day 1 for all therapies not listed above
- Currently receiving or had treatment with any of the following ≤ 12 weeks prior to day 1:
- azathioprine
- cyclosporine
- gold
- mycophenolate mofetil
- Prosorba column
- Tacrolimus
- Phase 2a only: Currently receiving or had treatment with leflunomide ≤ 12 weeks prior to day 1 unless an active washout with cholestyramine has been performed.
- Phase 2a only: Currently receiving or had treatment with any of the following ≤ 4 weeks prior to day 1:
- hydroxychloroquine
- sulfasalazine
- minocycline
- oral janus kinase inhibitor (eg, tofacitinib, baricitinib)
- intra-articular, intramuscular or intravenous corticosteroids, including adrenocorticotropic hormone
- intra-articular hyaluronic acid injections
- live vaccines -- For Phase 2 only:
- Unstable dose of non-steroidal anti-inflammatory drugs (NSAID), acetaminophen, and/or analgesics which is taken on an unscheduled basis (ie, not daily or scheduled every certain number of hours) and/or initiated <4 weeks prior to day 1.
- Received the following within 12 hours prior to screening or day 1:
- acetaminophen, NSAIDs, tramadol, and/or any narcotic analgesics such as but not limited to hydrocodone, codeine, tramadol, propoxyphene and/or oxycodone (unless in the form of oxycontin). Subject has taken oxycontin within 24 hours prior to screening or day 1.
- Phase 1b only: Received any herbal medicines (eg St John's wort),or non-vitamin dietary supplements (eg, magnesium) with the exception of calcium within 4 weeks prior to day 1.
- Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.
- Presence of laboratory abnormalities at screening including the following:
- Aspartate aminotransferase (AST) or alanine amino transferase (ALT) at screening > 1.5X upper limit of normal (ULN)
- Serum total bilirubin (TBL) ≥ 1.5 mg/dL (≥ 26 μmol/L)
- Hemoglobin ≤ 10.5 g/dL(≤105 g/L)
- Platelet count < 100,000/mm^3 (<100 x 10^9/L)
- White blood cell count < 2,500 cells/mm^3 (2.5 x 10^9/L)
- Absolute neutrophil count (ANC) < 1,000/mm^3 (1.0 x 10^9/L)
- Calculated glomerular filtration rate of ≤ 50 mL/min/1.73 m^2 using the Modification of Diet in Renal Disease (MDRD) formula
- Any other laboratory abnormality, which, in the opinion of the investigator, poses a safety risk, will prevent the subject from completing the study, will interfere with the interpretation of the study results, or might cause the study to be detrimental to the subject.
- Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 6 weeks after the last dose of investigational product.
- Females of child-bearing potential with a positive pregnancy test (assessed by a serum pregnancy test at screening and a urine pregnancy test at baseline).
- Female subjects of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 6 weeks after the last dose of investigational product.
- Subject has known sensitivity to any of the products or components to be administered during dosing.
- Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments [COAs]) to the best of the subject and investigator's knowledge.
- History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
Trial locations and contacts
15 sites in 5 countries.
15 sites in 5 countries
Poland6 sites
Research Site
Józefów, 05-410
Research Site
Krakow, 30-348
Research Site
Poznan, 60-848
Research Site
Stalowa Wola, 37-450
Research Site
Świdnik, 21-040
Research Site
Wroclaw, 51-128
United States5 sites
Research Site
Anniston, Alabama, 36207
Research Site
Dallas, Texas, 75231
Research Site
Duncansville, Pennsylvania, 16635
Research Site
Lansing, Michigan, 48910
Research Site
Torrance, California, 90502
Germany2 sites
Research Site
Berlin, 10117
Research Site
Frankfurt am Main, 60590
About this study
Official title: A Phase 1b/2a Study to Evaluate the Safety and Efficacy of Efavaleukin Alfa in Subjects With Active Rheumatoid Arthritis With Inadequate Response to Standard of Care Therapy
Phase 1b. To evaluate the safety and tolerability of subcutaneous (SC) dose administrations of Efavaleukin alfa in subjects with active rheumatoid arthritis (RA).
Phase 2a. To evaluate the efficacy of Efavaleukin alfa at week 12 as measured by the American College of Rheumatology 20 percent improvement criteria (ACR 20) in adult subjects with moderate to severe RA.
- Conditions
- Rheumatoid Arthritis RA
- Being tested
- Efavaleukin alfa, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Efavaleukin alfaDrug
Also called AMG 592
Efavaleukin alfa administered as a subcutaneous injection.
PlaceboDrug
Placebo administered as a subcutaneous injection.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1b: Placebo | Placebo comparator | Matching placebo administered via subcutaneous injection for a total of up to 12 weeks. Participants received placebo in 1 of 2 dosing schedules (i.e. dosing schedule A [less frequent] or schedule B [more frequent]). Receives: Drug: Placebo |
| Phase 1b: Efavaleukin alfa Cohort 1 | Experimental | A low dose of Efavaleukin alfa administered via subcutaneous injection using dosing schedule A (less frequent than schedule B) for a total of up to 12 weeks. Receives: Drug: Efavaleukin alfa |
| Phase 1b: Efavaleukin alfa Cohort 2 | Experimental | A high dose of Efavaleukin alfa administered via subcutaneous injection using dosing schedule A (less frequent than schedule B) for a total of up to 12 weeks. Receives: Drug: Efavaleukin alfa |
| Phase 1b: Efavaleukin alfa Cohort 3 | Experimental | A medium dose of Efavaleukin alfa administered via subcutaneous injection using dosing schedule B (more frequent than schedule A) for a total of up to 12 weeks. Receives: Drug: Efavaleukin alfa |
| Phase 1b: Efavaleukin alfa Cohort 4 | Experimental | A medium/high dose of Efavaleukin alfa administered via subcutaneous injection using dosing schedule B (more frequent than schedule A) for a total of up to 12 weeks. Receives: Drug: Efavaleukin alfa |
| Phase 2a: Placebo | Placebo comparator | Matching placebo administered via subcutaneous injection, depending on the recommended phase 2 dose (RP2D) and dosing schedule as determined in phase 1b, for a total of up to 12 weeks. Receives: Drug: Placebo |
| Phase 2a: Efavaleukin alfa | Experimental | Efavaleukin alfa administered via subcutaneous injection depending on the RP2D and dosing schedule determined in phase 1b, for up to a total of up to 12 weeks. Receives: Drug: Efavaleukin alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1b: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
TEAEs were events with an onset after the administration of the first dose of study treatment.
TEAEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE).
Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limited age appropriate instrumental activities of daily life (ADL).
Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolonged hospitalization indicated; disabling; limited self care ADL.
Grade 4 Life-threatening consequences; urgent interventions indicated.
Serious adverse events (SAEs) were defined as meeting at least 1 of the following criteria:
- Results in death (fatal)
- Immediately life-threatening
- Requires in-patient hospitalization or prolongation of existing hospitalization
- Results in persistent or significant disability/incapacity
- Is a congenital anomaly/birth defect
- Other medically important serious event
Measured: Day 1 up to end of study, maximum of 18 weeks (12-weeks double-blind treatment, 6-weeks safety follow-up)
Phase 1b: Number of Participants Who Experienced a Clinically Significant Change in Vital Signs
Any changes in systolic/diastolic blood pressure, heart rate, respiratory rate, and temperature that were deemed as clinically significant by the Investigator were reported.
Measured: Baseline up to end of study, maximum of 18 weeks (12-weeks double-blind treatment, 6-weeks safety follow-up)
Phase 1b: Number of Participants Who Experienced a Clinically Significant Change in Laboratory Safety Tests
Laboratory safety tests included chemistry and hematology parameters. Clinically significant laboratory safety tests were any events assessed as CTCAE Grade ≥3 at any post-baseline visit.
Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolonged hospitalization indicated; disabling; limited self care ADL.
Grade 4 Life-threatening consequences; urgent interventions indicated.
Measured: Baseline up to end of study, maximum of 18 weeks (12-weeks double-blind treatment, 6-weeks safety follow-up)
Phase 1b: Number of Participants Who Experienced a Clinically Significant Change in Electrocardiograms (ECGs)
Any changes in ECG parameters that were deemed clinically significant by the investigator were reported.
Measured: Baseline up to end of treatment maximum of 12 weeks
Phase 2a: Number of Participants Who Achieved an American College of Rheumatology 20 Percent Improvement Criteria (ACR 20) at Week 12
ACR 20 response defined as at least 20 percent improvement from baseline in both tender and swollen joint counts, and a 20 percent improvement or more in at least 3 of the following 5 criteria:
- physician global assessment of disease activity (PGA)
- subject global assessment of disease activity (SGA)
- patient global assessment of joint pain
- subject self-assessment of disability (HAQ-DI)
- C-Reactive Protein (CRP)
Measured: Baseline and Week 12
Secondary outcomes (17)
Phase 1b: Efavaleukin Alfa Serum Concentrations
A summary of mean serum concentrations of Efavaleukin alfa over time is presented. Any results below the lower limit of quantification were set to 0.00.
Measured: Day 1 (pre-dose), 6 and 12 hours post-dose, and days 2, 3, 4, 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and Day 85 (pre-dose), 6 and 12 hours post-dose and days 86, 87, 88, 92, 99, 113 and 127
Phase 1b: Maximum Observed Serum Concentration (Cmax) of Efavaleukin Alfa
Measured: Day 1 (pre-dose) and 6 to 48 hours post-dose, and days 4, 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, Day 85 (pre-dose) and 6 to 72 hours post-dose, and days 92, 99, 113 and 127
Phase 1b: Time to Maximum Observed Serum Concentration (Tmax) of Efavaleukin Alfa
Measured: Day 1 (pre-dose) and 6 to 48 hours post-dose, and days 4, 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, Day 85 (pre-dose) and 6 to 72 hours post-dose, and days 92, 99, 113 and 127
Phase 1b: Area Under the Concentration-time Curve From Time 0 to 14 Days (AUC0-14) Post Dose
AUC0-14 was only assessed for the participants who received Efavaleukin alfa using dosing schedule A.
Measured: Day 1 (pre-dose) and 6 to 48 hours post-dose, and days 4, 8, 11 and 15, Day 85 (pre-dose) and 6 to 72 hours post-dose, and days 92 and 99
Phase 1b: Area Under the Concentration-time Curve From Time 0 to 7 Days (AUC0-7) Post Dose
AUC0-7 was only assessed for the participants who received Efavaleukin alfa using dosing schedule B.
Measured: Day 1 (pre-dose) and 6 to 48 hours post-dose, and days 4 and 8, Day 85 (pre-dose) and 6 to 72 hours post-dose, and Day 92
Phase 1b: Number of Participants With Anti-Efavaleukin Alfa Binding Antibodies and Anti-Interleukin (IL-2) Binding Antibodies
Number of participants who tested positive for anti-Efavaleukin alfa binding antibodies and number of those participants who cross-reacted with native human IL-2 (i.e. with anti-IL-2 binding antibodies) are reported.
Measured: Baseline up to end of study, maximum of 18 weeks (12-weeks double-blind treatment, 6-weeks safety follow-up)
Phase 1b: Number of Participants With Anti-Efavaleukin Alfa Neutralizing Antibodies and Anti-IL-2 Neutralizing Antibodies
The number of participants who tested positive for anti-Efavaleukin alfa neutralizing antibodies and number of participants with anti-IL2 neutralizing antibodies who tested negative or no result at baseline are reported.
Measured: Baseline up to end of study, maximum of 18 weeks (12-weeks double-blind treatment, 6-weeks safety follow-up)
Phase 2a: Number of Participants Who Achieved an American College of Rheumatology 50 Percent Improvement Criteria (ACR 50) or 70 Percent Improvement Criteria (ACR 70) at Week 12
ACR 50 and ACR 70 response defined as at least 50 percent or 70 percent improvement from baseline in both tender and swollen joint counts, and a 50 percent or 70 percent improvement or more in at least 3 of the following 5 criteria:
- physician global assessment of disease activity (PGA)
- subject global assessment of disease activity (SGA)
- patient global assessment of joint pain
- subject self-assessment of disability (HAQ-DI)
- C-Reactive Protein (CRP)
Measured: Baseline and Week 12
Phase 2a: Change From Baseline in Disease Activity Score (28 Joint) Calculated Using The Erythrocyte Sedimentation Rate Formula (DAS28-ESR) at Week 12
Change from baseline in DAS28-ER at Week 12. DAS28-ESR was to assess disease activity in patients with rheumatoid arthritis. DAS28-ESR is a composite score that includes 4 variables: tender joint count (TJC) (based on 28 joints); swollen joint count (SJC) (based on 28 joints); participant's global assessment of health activity using 100 mm VAS: range 0 (no pain) to 100 (maximum pain imaginable); marker of inflammation assessed by ESR in mm/h. DAS28-ESR total score range from 0-10, higher score indicates more disease activity.
Measured: Baseline and Week 12
Phase 2a: Change From Baseline in Disease Activity Score (28 Joint) Calculated Using the C-reactive Protein Formula (DAS-28-CRP) at Week 12
Change from baseline in DAS28-CRP at Week 12. 2. DAS28-CRP was to assess disease activity in patients with rheumatoid arthritis. DAS28-CRP is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); participant's global assessment of health activity using 100 mm VAS: range 0 (no pain) to 100 (maximum pain imaginable); marker of inflammation assessed by CRP in mg/L. DAS28-CRP total score range from 0-10, higher score indicates more disease activity.
Measured: Baseline and Week 12
Phase 2a: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
TEAEs were events with an onset after the administration of the first dose of study treatment.
TEAEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE).
Measured: Baseline up to end of study, maximum of 18 weeks (12-weeks double-blind treatment, 6-weeks safety follow-up)
Phase 2a: Number of Participants Who Experienced a Clinically Significant Change in Vital Signs
Any changes in systolic/diastolic blood pressure, heart rate, respiratory rate, and temperature that were deemed as clinically significant by the Investigator were reported.
Measured: Baseline up to Week 12
Phase 2a: Number of Participants Who Experienced a Clinically Significant Change in Laboratory Safety Tests
Laboratory safety tests included chemistry and hematology parameters. Clinically significant laboratory safety tests were any events assessed as CTCAE Grade ≥3 at any post-baseline visit.
Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolonged hospitalization indicated; disabling; limited self care ADL.
Grade 4 Life-threatening consequences; urgent interventions indicated.
Measured: Day 1 up to end of study, maximum of 18 weeks (12-weeks double-blind treatment, 6-weeks safety follow-up)
Phase 2a: Efavaleukin Alfa Serum Concentration
A summary of mean serum concentrations of Efavaleukin alfa over time.
Measured: Day 1 (pre-dose) and weeks 2, 4, 6, 8, 10 and 12
Phase 2a: Maximum Observed Serum Concentration (Cmax) of Efavaleukin Alfa
Measured: Day 1 (pre-dose) and weeks 2, 4, 6, 8, 10 and 12
Phase 2a: Time to Maximum Observed Serum Concentration (Tmax) of Efavaleukin Alfa
Measured: Day 1 (pre-dose) and weeks 2, 4, 6, 8, 10 and 12
Phase 2a: Area Under the Concentration-time Curve (AUC) of Efavaleukin Alfa
Measured: Day 1 (pre-dose) and weeks 2, 4, 6, 8, 10 and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2018
- Study start22 May 2018
- Primary completion10 Dec 2019
- Study completion13 May 2020
Why it stopped: Amgen made a business decision not to proceed with Phase 2.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Rheumatoid Arthritis RAStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03410056
- Sponsor's protocol ID
- 20170149
- Other IDs
- 2017-001944-36, 2017
- Status last verified
- Jun 2021
- First submitted
- 3 Jan 2018
- Last updated
- 22 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2a Study to Evaluate the Safety and Efficacy of Efavaleukin Alfa in Subjects With Active Rheumatoid Arthritis With Inadequate Response to Standard of Care Therapy
- ClinicalTrials.gov ID
- NCT03410056
- Acronym / sponsor ID
- 20170149
- Conditions
- Rheumatoid Arthritis RA
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Amgen made a business decision not to proceed with Phase 2.
- Enrolment
- 36 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 22 May 2018 (actual)
- Primary completion
- 10 Dec 2019 (actual)
- Study completion
- 13 May 2020 (actual)
- First posted
- 25 Jan 2018 (actual)
- Results
- Posted 4 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 1b. To evaluate the safety and tolerability of subcutaneous (SC) dose administrations of Efavaleukin alfa in subjects with active rheumatoid arthritis (RA).
Phase 2a. To evaluate the efficacy of Efavaleukin alfa at week 12 as measured by the American College of Rheumatology 20 percent improvement criteria (ACR 20) in adult subjects with moderate to severe RA.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Phase 1b: Placebo | Placebo comparator | Drug: PlaceboMatching placebo administered via subcutaneous injection for a total of up to 12 weeks. Participants received placebo in 1 of 2 dosing schedules (i.e. dosing schedule A [less frequent] or schedule B [more frequent]). |
| Phase 1b: Efavaleukin alfa Cohort 1 | Experimental | Drug: Efavaleukin alfaA low dose of Efavaleukin alfa administered via subcutaneous injection using dosing schedule A (less frequent than schedule B) for a total of up to 12 weeks. |
| Phase 1b: Efavaleukin alfa Cohort 2 | Experimental | Drug: Efavaleukin alfaA high dose of Efavaleukin alfa administered via subcutaneous injection using dosing schedule A (less frequent than schedule B) for a total of up to 12 weeks. |
| Phase 1b: Efavaleukin alfa Cohort 3 | Experimental | Drug: Efavaleukin alfaA medium dose of Efavaleukin alfa administered via subcutaneous injection using dosing schedule B (more frequent than schedule A) for a total of up to 12 weeks. |
| Phase 1b: Efavaleukin alfa Cohort 4 | Experimental | Drug: Efavaleukin alfaA medium/high dose of Efavaleukin alfa administered via subcutaneous injection using dosing schedule B (more frequent than schedule A) for a total of up to 12 weeks. |
| Phase 2a: Placebo | Placebo comparator | Drug: PlaceboMatching placebo administered via subcutaneous injection, depending on the recommended phase 2 dose (RP2D) and dosing schedule as determined in phase 1b, for a total of up to 12 weeks. |
| Phase 2a: Efavaleukin alfa | Experimental | Drug: Efavaleukin alfaEfavaleukin alfa administered via subcutaneous injection depending on the RP2D and dosing schedule determined in phase 1b, for up to a total of up to 12 weeks. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Subject has provided informed consent prior to initiation of any study specific activities/procedures.
- Age ≥ 18 to ≤ 70 years of age at screening.
- A diagnosis of RA consistent with the 1987 or 2010 American College of Rheumatology (ACR)/European League Against Rheumatism classification criteria.
- Active RA defined as: Phase 1b: DAS-28-CRP > 2.6 at screening. The 28-joint count consists of the finger joints excluding the distal interphalangeal joints, the wrists, elbows, shoulders, and knees. Phase 2a: ≥ 6 swollen joints (based on 66-joint count) and ≥ 6 tender joints (based on 68-joint count) at screening and baseline. The distal interphalangeal joint should be evaluated but not included in the total count to determine eligibility. Additionally, C-reactive protein (CRP) must be greater than the upper limit of normal (ULN) per the central laboratory at screening.
- Receiving treatment with methotrexate for ≥ 12 weeks and on a stable dose ≥ 15 mg weekly for ≥ 8 weeks prior to day 1. A lower methotrexate dose is acceptable (but no lower than 10 mg weekly) if it is the highest tolerated dose and gastrointestinal or hematologic toxicity at doses ≥ 15 mg weekly is documented by the investigator.
Key exclusion criteria (57 listed)
- Class IV RA according to ACR revised response criteria
- Diagnosis of Felty's Syndrome (RA, splenomegaly and granulocytopenia).
- Prosthetic joint infection within 3 years of screening or native joint infection within 1 year prior to screening.
- Active infection (including chronic or localized infections) for which anti-infectives were indicated within 4 weeks prior to day 1 OR presence of serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to day 1.
- Known history of active tuberculosis.
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 |
|---|---|---|
| Efavaleukin alfaAlso: AMG 592Efavaleukin alfa administered as a subcutaneous injection. | Drug | Phase 1b: Efavaleukin alfa Cohort 1, Phase 1b: Efavaleukin alfa Cohort 2, Phase 1b: Efavaleukin alfa Cohort 3, Phase 1b: Efavaleukin alfa Cohort 4, Phase 2a: Efavaleukin alfa |
| PlaceboPlacebo administered as a subcutaneous injection. | Drug | Phase 1b: Placebo, Phase 2a: Placebo |
Primary outcome
Phase 1b: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
Time frame: Day 1 up to end of study, maximum of 18 weeks (12-weeks double-blind treatment, 6-weeks safety follow-up)
TEAEs were events with an onset after the administration of the first dose of study treatment. TEAEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE). Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limited age appropriate instrumental activities of daily life (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolonged hospitalization indicated; disabling; limited self care ADL. Grade 4 Life-threatening consequences; urgent interventions indicated. Serious adverse events (SAEs) were defined as meeting at least 1 of the following criteria: * Results in death (fatal) * Immediately life-threatening * Requires in-patient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect * Other medically important serious event
Phase 1b: Number of Participants Who Experienced a Clinically Significant Change in Vital Signs
Time frame: Baseline up to end of study, maximum of 18 weeks (12-weeks double-blind treatment, 6-weeks safety follow-up)
Any changes in systolic/diastolic blood pressure, heart rate, respiratory rate, and temperature that were deemed as clinically significant by the Investigator were reported.
Phase 1b: Number of Participants Who Experienced a Clinically Significant Change in Laboratory Safety Tests
Time frame: Baseline up to end of study, maximum of 18 weeks (12-weeks double-blind treatment, 6-weeks safety follow-up)
Laboratory safety tests included chemistry and hematology parameters. Clinically significant laboratory safety tests were any events assessed as CTCAE Grade ≥3 at any post-baseline visit. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolonged hospitalization indicated; disabling; limited self care ADL. Grade 4 Life-threatening consequences; urgent interventions indicated.
Phase 1b: Number of Participants Who Experienced a Clinically Significant Change in Electrocardiograms (ECGs)
Time frame: Baseline up to end of treatment maximum of 12 weeks
Any changes in ECG parameters that were deemed clinically significant by the investigator were reported.
Phase 2a: Number of Participants Who Achieved an American College of Rheumatology 20 Percent Improvement Criteria (ACR 20) at Week 12
Time frame: Baseline and Week 12
ACR 20 response defined as at least 20 percent improvement from baseline in both tender and swollen joint counts, and a 20 percent improvement or more in at least 3 of the following 5 criteria: * physician global assessment of disease activity (PGA) * subject global assessment of disease activity (SGA) * patient global assessment of joint pain * subject self-assessment of disability (HAQ-DI) * C-Reactive Protein (CRP)
17 secondary outcomes
Phase 1b: Efavaleukin Alfa Serum Concentrations
Time frame: Day 1 (pre-dose), 6 and 12 hours post-dose, and days 2, 3, 4, 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and Day 85 (pre-dose), 6 and 12 hours post-dose and days 86, 87, 88, 92, 99, 113 and 127
Phase 1b: Maximum Observed Serum Concentration (Cmax) of Efavaleukin Alfa
Time frame: Day 1 (pre-dose) and 6 to 48 hours post-dose, and days 4, 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, Day 85 (pre-dose) and 6 to 72 hours post-dose, and days 92, 99, 113 and 127
Phase 1b: Time to Maximum Observed Serum Concentration (Tmax) of Efavaleukin Alfa
Time frame: Day 1 (pre-dose) and 6 to 48 hours post-dose, and days 4, 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, Day 85 (pre-dose) and 6 to 72 hours post-dose, and days 92, 99, 113 and 127
Phase 1b: Area Under the Concentration-time Curve From Time 0 to 14 Days (AUC0-14) Post Dose
Time frame: Day 1 (pre-dose) and 6 to 48 hours post-dose, and days 4, 8, 11 and 15, Day 85 (pre-dose) and 6 to 72 hours post-dose, and days 92 and 99
Phase 1b: Area Under the Concentration-time Curve From Time 0 to 7 Days (AUC0-7) Post Dose
Time frame: Day 1 (pre-dose) and 6 to 48 hours post-dose, and days 4 and 8, Day 85 (pre-dose) and 6 to 72 hours post-dose, and Day 92
Phase 1b: Number of Participants With Anti-Efavaleukin Alfa Binding Antibodies and Anti-Interleukin (IL-2) Binding Antibodies
Time frame: Baseline up to end of study, maximum of 18 weeks (12-weeks double-blind treatment, 6-weeks safety follow-up)
Phase 1b: Number of Participants With Anti-Efavaleukin Alfa Neutralizing Antibodies and Anti-IL-2 Neutralizing Antibodies
Time frame: Baseline up to end of study, maximum of 18 weeks (12-weeks double-blind treatment, 6-weeks safety follow-up)
Phase 2a: Number of Participants Who Achieved an American College of Rheumatology 50 Percent Improvement Criteria (ACR 50) or 70 Percent Improvement Criteria (ACR 70) at Week 12
Time frame: Baseline and Week 12
Phase 2a: Change From Baseline in Disease Activity Score (28 Joint) Calculated Using The Erythrocyte Sedimentation Rate Formula (DAS28-ESR) at Week 12
Time frame: Baseline and Week 12
Phase 2a: Change From Baseline in Disease Activity Score (28 Joint) Calculated Using the C-reactive Protein Formula (DAS-28-CRP) at Week 12
Time frame: Baseline and Week 12
Phase 2a: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
Time frame: Baseline up to end of study, maximum of 18 weeks (12-weeks double-blind treatment, 6-weeks safety follow-up)
Phase 2a: Number of Participants Who Experienced a Clinically Significant Change in Vital Signs
Time frame: Baseline up to Week 12
Phase 2a: Number of Participants Who Experienced a Clinically Significant Change in Laboratory Safety Tests
Time frame: Day 1 up to end of study, maximum of 18 weeks (12-weeks double-blind treatment, 6-weeks safety follow-up)
Phase 2a: Efavaleukin Alfa Serum Concentration
Time frame: Day 1 (pre-dose) and weeks 2, 4, 6, 8, 10 and 12
Phase 2a: Maximum Observed Serum Concentration (Cmax) of Efavaleukin Alfa
Time frame: Day 1 (pre-dose) and weeks 2, 4, 6, 8, 10 and 12
Phase 2a: Time to Maximum Observed Serum Concentration (Tmax) of Efavaleukin Alfa
Time frame: Day 1 (pre-dose) and weeks 2, 4, 6, 8, 10 and 12
Phase 2a: Area Under the Concentration-time Curve (AUC) of Efavaleukin Alfa
Time frame: Day 1 (pre-dose) and weeks 2, 4, 6, 8, 10 and 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Related trials for Rheumatoid Arthritis RA
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis and Systemic Lupus Erythematosus
Active, not recruitingObservational study
Overactive Bladder Symptoms and Urinary Incontinence In Women With Rheumatoid Arthritis
Rheumatoid Arthritis, Rheumatoid Arthritis (RA)
Recruiting
GenAI-Assisted Rheumatoid Arthritis Bone Erosion Risk Assessment and DMARD Selection
Rheumatoid Arthritis
Not yet recruitingObservational study
The Impact of Rheumatoid Arthritis Treatments on the Modulation of Extracellular Vesicles and Other Biomarkers Involved in the Development of Lung Cancer
Rheumatoid Arthritis (RA), Lung Neoplasms
Not yet recruiting
MYTP01 for Immune-Mediated Diseases
IgA Nephropathy, Kidney Transplant Recipients
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.
MD study director
Amgen
15 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Efavaleukin alfa in people with Rheumatoid Arthritis RA, run by Amgen at 15 sites in 5 countries.
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 10 inclusion and 57 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: stopped early, as of the sponsor's last update on 22 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Poland, United States, Germany, Bulgaria, Spain. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Yes. Results are posted in the registry (first posted 4 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Phase 1b: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) (time frame: Day 1 up to end of study, maximum of 18 weeks (12-weeks double-blind treatment, 6-weeks safety follow-up)). The study lists 5 primary outcomes in all. 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 22 Jun 2021.