Systemic Lupus Erythematosus
Conditions
Keywords
Efavaleukin Alfa, Systemic lupus erythematosus, Phase 1b
Brief summary
To evaluate the safety and tolerability of subcutaneous (SC) dose administrations of Efavaleukin Alfa in participants with systemic lupus erythematosus (SLE).
Interventions
DRUGPlacebo
The placebo will be administered by subcutaneous (SC) injection in the abdomen, thigh or upper arm.
DRUGEfavaleukin Alfa
Efavaleukin Alfa will be administered by subcutaneous (SC) injection in the abdomen, thigh or upper arm.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
This phase 1b study is a double-blind, placebo controlled multiple ascending dose (MAD) study to evaluate the safety and tolerability of Efavaleukin Alfa in participants with systemic lupus erythematosus (SLE) and to determine the recommended phase 2 dose(s). Participants will be treated for a total of 12 weeks followed by a 6 week follow-up period. Five dosing cohorts are planned for the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Participants are eligible to be included in the study only if all of the following criteria apply: * Participant has provided informed consent prior to initiation of any study specific activities/procedures. * Age ≥ 18 years to ≤ 70 years at screening. * Fulfills diagnostic criteria for SLE according to the Systemic Lupus International Collaborating Clinics (SLICC) criteria or by at least 4 of the 11 criteria of the 1997 American College of Rheumatology (ACR) classification criteria for SLE, with a history of at least one of the following: * Antinuclear antibody ≥ 1:80; or * Elevated anti-dsDNA antibodies * May be taking ≤ 3 systemic SLE treatments and the dose must be stable for ≥ 4 weeks prior to day 1. * Prednisone dose ≤ 20 mg daily (or other equivalent oral corticosteroid) with stable dose ≥ 2 weeks prior to day 1. * Normal or clinically acceptable 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 \[Td/Tdap\]), seasonal influenza (during flu season), and pneumococcal (polysaccharide) vaccinations\] up to date per local standards as determined by the investigator.
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply. Disease Related \- History of lupus nephritis requiring induction therapy and/or lupus cerebritis ≤ 1 year prior to screening. Other Medical Conditions * Diagnosis of inflammatory joint or skin disease other than SLE which would interfere with SLE disease assessment based on investigator judgement. * Diagnosis of fibromyalgia which would interfere with SLE assessment according to the investigator. * 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 worksheet provided by Amgen * documented 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. * Positive for hepatitis B surface antigen, hepatitis B core antibody (confirmed by hepatitis B DNA polymerase chain reaction \[PCR\] test) or detectable hepatitis C virus 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. * Positive for Human Immunodeficiency Virus (HIV) at screening, or known to be HIV positive. * 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 SLE (eg, RA). * Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within 5 years of screening. * Participants with a urine test positive for illicit drugs or alcohol at the screening visit. Prescription medications detected by the drug test are allowed if they are being taken under the direction of a physician. * History of alcohol or substance abuse within 6 months of screening. * 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, cigarettes, electronic cigarettes, pipes, or nicotine patches. * Participant 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. Prior/Concomitant Therapy * Currently receiving or had treatment with: cyclophosphamide, chlorambucil, nitrogen mustard, or any other alkylating agent ≤ 6 months prior to day 1 OR oral calcineurin inhibitors (eg, cyclosporine, tacrolimus, sirolimus) ≤ 4 weeks prior to day 1. * Current or previous treatment for SLE with a biologic agent as follows: rituximab \< 6 months prior to day 1, belimumab \< 3 months prior to day 1, abatacept \< 8 weeks prior to day 1. * Currently receiving or had treatment with T cell depleting agents (eg, antithymocyte globulin, Campath) or recombinant IL-2 (eg, Proleukin). * Participants who have received intra-articular or systemic corticosteroid injections within 4 weeks prior to day 1 or topical steroids within 2 weeks prior to day 1. * Administration of herbal supplements, vitamins, or nutritional supplements within 30 days prior to the first dose of investigational product, and continuing use, if applicable, will be reviewed by the Investigator and the Amgen Medical Monitor to determine acceptability. Written documentation of this review and Amgen acknowledgment is required for participant participation. Prior/Concurrent Clinical Study Experience * Currently receiving treatment in another investigational device or drug study, or less than 30 days at day 1 since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded. * Participant previously enrolled in this study may not be re-enrolled unless they fulfill the following criteria: * Have completed the study previously without any adverse events deemed related to study drug. * Have received the last dose of Efavaleukin Alfa/placebo \> 6 months prior to the screening visit. * Must not have tested positive for neutralizing antibodies against Efavaleukin Alfa at any time. Diagnostic Assessments * Presence of laboratory abnormalities at screening including the following: * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 1.5x upper limit of normal (ULN) * Serum total bilirubin (TBL) ≥ 1.5 mg/dL (≥ 26 μmol/L) * Hemoglobin \< 9.0 g/dL(\< 90 g/L) * Platelet count \< 100,000/mm\^3 (100 x 10\^9/L) * White blood cell count \< 2,000 cells/mm\^3 (2.0 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 participant from completing the study, will interfere with the interpretation of the study results, or might cause the study to be detrimental to the participant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) | A TEAE was defined as any adverse event (AE) starting on or after the first dose of investigational product through to the safety follow-up visit. Any clinically significant changes in physical examinations, vital signs, and clinical laboratory test results were recorded as AEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Concentration (Cmax) for AMG 592 | Day 1 (pre-dose) and 6 to 72 hours post-dose, and Days 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 | — |
| Time of Cmax (Tmax) for AMG 592 | Day 1 (pre-dose) and 6 to 72 hours post-dose, and Days 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 | — |
| Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for AMG 592 | Day 1 (pre-dose) and 6 to 72 hours post-dose, and Days 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 | — |
| Number of Participants With Anti-AMG 592 Binding Antibodies and Anti-Interleukin (IL-2) Binding Antibodies | Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) | Number of participants who tested positive for developing anti-AMG 592 or anti-IL-2 binding antibodies at 1 or more post-baseline time points, with a negative or no result at baseline, are reported. |
| Number of Participants With Anti-AMG 592 Neutralizing Antibodies and Anti-IL-2 Neutralizing Antibodies | Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) | Number of participants who tested positive for developing anti-AMG 592 or anti-IL-2 neutralizing antibodies at 1 or more post-baseline time points, with a negative or no result at baseline, are reported. |
Countries
France, Germany, Poland, United States
Participant flow
Recruitment details
Participants were enrolled at 10 centers in the United States, France, and Poland from 10 April 2018 to 12 October 2021.
Pre-assignment details
A total of 33 participants were randomized to AMG 592 or placebo in a 5:2 ratio (Cohorts 1, 2, and 3) or in a 1:3 ratio (Cohorts 4 and 5). Of those 33 participants, 2 were re-enrolled and re-randomized to subsequent cohorts upon completion. The total number of informed consent forms signed that led to randomization was 35.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo was administered by subcutaneous (SC) injection using dosing schedule A or B (A was less frequent than schedule B) for a total of 12 weeks.
Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to matching placebo in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified. | 10 |
| AMG 592 Cohort 1 A low dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks. | 5 |
| AMG 592 Cohort 2 A medium dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks. | 5 |
| AMG 592 Cohort 3 A medium dose of AMG 592 was administered by SC injection using dosing schedule B (more frequent than schedule A) for a total of 12 weeks. | 7 |
| AMG 592 Cohort 4 A medium/high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks. | 4 |
| AMG 592 Cohort 5 A high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.
Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to AMG 592 in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified. | 4 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Decision by sponsor | 1 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 2 | 3 | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | AMG 592 Cohort 1 | AMG 592 Cohort 2 | AMG 592 Cohort 3 | AMG 592 Cohort 4 | AMG 592 Cohort 5 | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 47.2 years STANDARD_DEVIATION 17.4 | 44.4 years STANDARD_DEVIATION 13.4 | 44.4 years STANDARD_DEVIATION 9.2 | 13.9 years STANDARD_DEVIATION 63 | 16.6 years STANDARD_DEVIATION 57 | 6.6 years STANDARD_DEVIATION 60 | 14.4 years STANDARD_DEVIATION 54 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 5 Participants | 5 Participants | 7 Participants | 4 Participants | 4 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized African and White | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants | 2 Participants | 12 Participants |
| Race/Ethnicity, Customized Black or African American and American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 5 Participants | 5 Participants | 4 Participants | 1 Participants | 2 Participants | 21 Participants |
| Sex: Female, Male Female | 8 Participants | 3 Participants | 5 Participants | 6 Participants | 4 Participants | 4 Participants | 30 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 5 | 0 / 5 | 0 / 7 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 7 / 10 | 5 / 5 | 5 / 5 | 7 / 7 | 3 / 4 | 4 / 4 |
| serious Total, serious adverse events | 0 / 10 | 0 / 5 | 1 / 5 | 0 / 7 | 0 / 4 | 1 / 4 |
Outcome results
Primary
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
A TEAE was defined as any adverse event (AE) starting on or after the first dose of investigational product through to the safety follow-up visit. Any clinically significant changes in physical examinations, vital signs, and clinical laboratory test results were recorded as AEs.
Time frame: Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up)
Population: The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 7 Participants |
| AMG 592 Cohort 1 | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 5 Participants |
| AMG 592 Cohort 2 | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 5 Participants |
| AMG 592 Cohort 3 | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 7 Participants |
| AMG 592 Cohort 4 | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 3 Participants |
| AMG 592 Cohort 5 | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 4 Participants |
Secondary
Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for AMG 592
Time frame: Day 1 (pre-dose) and 6 to 72 hours post-dose, and Days 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
Population: The PK Parameter Analysis Set: All participants who have received AMG 592 and for whom at least one PK parameter could be adequately estimated. Only participants with PK data available for analysis are presented. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for AMG 592 | First dose (Day 1) | 538 hour*ng/mL |
| Placebo | Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for AMG 592 | Last dose (Day 85) | 773 hour*ng/mL |
| AMG 592 Cohort 1 | Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for AMG 592 | Last dose (Day 85) | 1120 hour*ng/mL |
| AMG 592 Cohort 1 | Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for AMG 592 | First dose (Day 1) | 915 hour*ng/mL |
| AMG 592 Cohort 2 | Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for AMG 592 | First dose (Day 1) | 1560 hour*ng/mL |
| AMG 592 Cohort 2 | Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for AMG 592 | Last dose (Day 85) | 542 hour*ng/mL |
| AMG 592 Cohort 3 | Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for AMG 592 | First dose (Day 1) | 1960 hour*ng/mL |
| AMG 592 Cohort 3 | Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for AMG 592 | Last dose (Day 85) | 3260 hour*ng/mL |
| AMG 592 Cohort 4 | Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for AMG 592 | First dose (Day 1) | 3770 hour*ng/mL |
| AMG 592 Cohort 4 | Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for AMG 592 | Last dose (Day 85) | 3010 hour*ng/mL |
Secondary
Maximum Observed Concentration (Cmax) for AMG 592
Time frame: Day 1 (pre-dose) and 6 to 72 hours post-dose, and Days 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
Population: The Pharmacokinetic (PK) Parameter Analysis Set: All participants who have received AMG 592 and for whom at least one PK parameter could be adequately estimated. Only participants with PK data available for analysis are presented. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | Maximum Observed Concentration (Cmax) for AMG 592 | Last dose (Day 85) | 9.24 ng/mL |
| Placebo | Maximum Observed Concentration (Cmax) for AMG 592 | First dose (Day 1) | 7.92 ng/mL |
| AMG 592 Cohort 1 | Maximum Observed Concentration (Cmax) for AMG 592 | Last dose (Day 85) | 18.9 ng/mL |
| AMG 592 Cohort 1 | Maximum Observed Concentration (Cmax) for AMG 592 | First dose (Day 1) | 13.0 ng/mL |
| AMG 592 Cohort 2 | Maximum Observed Concentration (Cmax) for AMG 592 | Last dose (Day 85) | 10.0 ng/mL |
| AMG 592 Cohort 2 | Maximum Observed Concentration (Cmax) for AMG 592 | First dose (Day 1) | 25.7 ng/mL |
| AMG 592 Cohort 3 | Maximum Observed Concentration (Cmax) for AMG 592 | First dose (Day 1) | 30.7 ng/mL |
| AMG 592 Cohort 3 | Maximum Observed Concentration (Cmax) for AMG 592 | Last dose (Day 85) | 56.5 ng/mL |
| AMG 592 Cohort 4 | Maximum Observed Concentration (Cmax) for AMG 592 | Last dose (Day 85) | 51.6 ng/mL |
| AMG 592 Cohort 4 | Maximum Observed Concentration (Cmax) for AMG 592 | First dose (Day 1) | 44.3 ng/mL |
Secondary
Number of Participants With Anti-AMG 592 Binding Antibodies and Anti-Interleukin (IL-2) Binding Antibodies
Number of participants who tested positive for developing anti-AMG 592 or anti-IL-2 binding antibodies at 1 or more post-baseline time points, with a negative or no result at baseline, are reported.
Time frame: Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up)
Population: The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Only participants who tested positive for anti-AMG 592 antibodies at anytime (pre- or post-dose) were analyzed for presence of anti-IL-2 neutralizing antibodies, as pre-specified. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Anti-AMG 592 Binding Antibodies and Anti-Interleukin (IL-2) Binding Antibodies | Binding anti-AMG 592 antibody | 0 Participants |
| AMG 592 Cohort 1 | Number of Participants With Anti-AMG 592 Binding Antibodies and Anti-Interleukin (IL-2) Binding Antibodies | Binding anti-AMG 592 antibody | 3 Participants |
| AMG 592 Cohort 1 | Number of Participants With Anti-AMG 592 Binding Antibodies and Anti-Interleukin (IL-2) Binding Antibodies | Binding anti-IL-2 antibody | 1 Participants |
| AMG 592 Cohort 2 | Number of Participants With Anti-AMG 592 Binding Antibodies and Anti-Interleukin (IL-2) Binding Antibodies | Binding anti-IL-2 antibody | 2 Participants |
| AMG 592 Cohort 2 | Number of Participants With Anti-AMG 592 Binding Antibodies and Anti-Interleukin (IL-2) Binding Antibodies | Binding anti-AMG 592 antibody | 3 Participants |
| AMG 592 Cohort 3 | Number of Participants With Anti-AMG 592 Binding Antibodies and Anti-Interleukin (IL-2) Binding Antibodies | Binding anti-IL-2 antibody | 0 Participants |
| AMG 592 Cohort 3 | Number of Participants With Anti-AMG 592 Binding Antibodies and Anti-Interleukin (IL-2) Binding Antibodies | Binding anti-AMG 592 antibody | 6 Participants |
| AMG 592 Cohort 4 | Number of Participants With Anti-AMG 592 Binding Antibodies and Anti-Interleukin (IL-2) Binding Antibodies | Binding anti-AMG 592 antibody | 2 Participants |
| AMG 592 Cohort 4 | Number of Participants With Anti-AMG 592 Binding Antibodies and Anti-Interleukin (IL-2) Binding Antibodies | Binding anti-IL-2 antibody | 1 Participants |
| AMG 592 Cohort 5 | Number of Participants With Anti-AMG 592 Binding Antibodies and Anti-Interleukin (IL-2) Binding Antibodies | Binding anti-AMG 592 antibody | 4 Participants |
| AMG 592 Cohort 5 | Number of Participants With Anti-AMG 592 Binding Antibodies and Anti-Interleukin (IL-2) Binding Antibodies | Binding anti-IL-2 antibody | 0 Participants |
Secondary
Number of Participants With Anti-AMG 592 Neutralizing Antibodies and Anti-IL-2 Neutralizing Antibodies
Number of participants who tested positive for developing anti-AMG 592 or anti-IL-2 neutralizing antibodies at 1 or more post-baseline time points, with a negative or no result at baseline, are reported.
Time frame: Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up)
Population: The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Only participants who tested positive for anti-AMG 592 antibodies at anytime (pre- or post-dose) were analyzed for presence of anti-IL-2 neutralizing antibodies, as pre-specified. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Anti-AMG 592 Neutralizing Antibodies and Anti-IL-2 Neutralizing Antibodies | Neutralizing anti-AMG 592 antibody | 0 Participants |
| AMG 592 Cohort 1 | Number of Participants With Anti-AMG 592 Neutralizing Antibodies and Anti-IL-2 Neutralizing Antibodies | Neutralizing anti-AMG 592 antibody | 0 Participants |
| AMG 592 Cohort 1 | Number of Participants With Anti-AMG 592 Neutralizing Antibodies and Anti-IL-2 Neutralizing Antibodies | Neutralizing anti-IL-2 antibody | 0 Participants |
| AMG 592 Cohort 2 | Number of Participants With Anti-AMG 592 Neutralizing Antibodies and Anti-IL-2 Neutralizing Antibodies | Neutralizing anti-AMG 592 antibody | 2 Participants |
| AMG 592 Cohort 2 | Number of Participants With Anti-AMG 592 Neutralizing Antibodies and Anti-IL-2 Neutralizing Antibodies | Neutralizing anti-IL-2 antibody | 0 Participants |
| AMG 592 Cohort 3 | Number of Participants With Anti-AMG 592 Neutralizing Antibodies and Anti-IL-2 Neutralizing Antibodies | Neutralizing anti-IL-2 antibody | 0 Participants |
| AMG 592 Cohort 3 | Number of Participants With Anti-AMG 592 Neutralizing Antibodies and Anti-IL-2 Neutralizing Antibodies | Neutralizing anti-AMG 592 antibody | 1 Participants |
| AMG 592 Cohort 4 | Number of Participants With Anti-AMG 592 Neutralizing Antibodies and Anti-IL-2 Neutralizing Antibodies | Neutralizing anti-AMG 592 antibody | 0 Participants |
| AMG 592 Cohort 4 | Number of Participants With Anti-AMG 592 Neutralizing Antibodies and Anti-IL-2 Neutralizing Antibodies | Neutralizing anti-IL-2 antibody | 0 Participants |
| AMG 592 Cohort 5 | Number of Participants With Anti-AMG 592 Neutralizing Antibodies and Anti-IL-2 Neutralizing Antibodies | Neutralizing anti-IL-2 antibody | 0 Participants |
| AMG 592 Cohort 5 | Number of Participants With Anti-AMG 592 Neutralizing Antibodies and Anti-IL-2 Neutralizing Antibodies | Neutralizing anti-AMG 592 antibody | 2 Participants |
Secondary
Time of Cmax (Tmax) for AMG 592
Time frame: Day 1 (pre-dose) and 6 to 72 hours post-dose, and Days 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
Population: The PK Parameter Analysis Set: All participants who have received AMG 592 and for whom at least one PK parameter could be adequately estimated. Only participants with PK data available for analysis are presented. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time of Cmax (Tmax) for AMG 592 | First dose (Day 1) | 24.0 hours |
| Placebo | Time of Cmax (Tmax) for AMG 592 | Last dose (Day 85) | 25.2 hours |
| AMG 592 Cohort 1 | Time of Cmax (Tmax) for AMG 592 | Last dose (Day 85) | 26.2 hours |
| AMG 592 Cohort 1 | Time of Cmax (Tmax) for AMG 592 | First dose (Day 1) | 47.6 hours |
| AMG 592 Cohort 2 | Time of Cmax (Tmax) for AMG 592 | Last dose (Day 85) | 18.0 hours |
| AMG 592 Cohort 2 | Time of Cmax (Tmax) for AMG 592 | First dose (Day 1) | 24.1 hours |
| AMG 592 Cohort 3 | Time of Cmax (Tmax) for AMG 592 | First dose (Day 1) | 24.6 hours |
| AMG 592 Cohort 3 | Time of Cmax (Tmax) for AMG 592 | Last dose (Day 85) | 24.1 hours |
| AMG 592 Cohort 4 | Time of Cmax (Tmax) for AMG 592 | Last dose (Day 85) | 16.7 hours |
| AMG 592 Cohort 4 | Time of Cmax (Tmax) for AMG 592 | First dose (Day 1) | 17.8 hours |