Sarcoidosis, Pulmonary
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled study with an open-label extension (OLE).
Detailed description
This is a randomized, double-blind, placebo-controlled study with an OLE. Participants will be randomized to receive namilumab or placebo in the 26-week Double-blind Treatment Period of the study. Namilumab, or placebo, will be administered subcutaneously (SC) every 4 weeks through Week 22 after the initial dosing period. All participants who complete the 26-week Double-blind Treatment Period, may be eligible to participate in the 28-week OLE. Further details are in the protocol.
Interventions
DRUGNamilumab
Namilumab administered subcutaneously
DRUGPlacebo
Placebo administered subcutaneously to match namilumab dosing
Sponsors
Kinevant Sciences GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Study drug will be provided in a blinded fashion and packaged and labeled to protect the blind.
Intervention model description
A double-blinded, randomized, placebo-controlled, parallel group design has been selected for the study. All participants, regardless of treatment assignment in the Double-blind Treatment Period, may participate in the Open Label Extension period of the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Male or female age ≥18 years * Able and willing to provide written informed consent, which includes compliance with study requirements and restrictions listed in the consent form * Greater than or equal to 6-month history of documented sarcoidosis including histological confirmation in the subject's medical records * Evidence of sarcoidosis as indicated by: a) HRCT consistent with Pulmonary Sarcoidosis AND; b) Medical Research Council Dyspnea scale \>1 (i.e., Grade 2 or more) AND; c) One or more of the following is present: i) Screening FDG-PET scan consistent with active pulmonary sarcoidosis AND SUVmax ≥ 3; ii) Recent history of worsening sarcoidosis; iii) Recent history that tapering OCS and/or ISTs resulted in an increase of pulmonary disease * Body Mass Index (BMI) ≤ 40 kg/m2 at Screening * Vaccinations for COVID-19 with completion of the primary series at least 2 weeks prior to randomization
Exclusion criteria
* Hospitalized for any respiratory illness ≤ 30 days prior to or during Screening * Greater than or equal to 20% fibrosis as indicated on HRCT-scan assessed by central read prior to randomization * Hemoglobin ≤ 9.5 g/dL * Participation in another interventional clinical trial (IP/Device) within 6 months prior to Screening, during screening and throughout the duration of the study * ECG abnormalities that warrant further clinical investigation or management at Screening * Systolic blood pressure (SBP) \<90 or \>180mm Hg; Diastolic blood pressure (DBP) \<60 or \>110 mm Hg at Screening * Has documented laboratory-confirmed SARS-CoV-2 infection with pulmonary involvement or signs/symptoms of long COVID as determined by approved testing ≤ 6 months prior to randomization * Other significant pulmonary disease or conditions that prevent subject from performing acceptable spirometry * Females who are pregnant or breastfeeding or intend to be during the course of the study * Any other acute or chronic medical condition, psychiatric condition, or laboratory abnormality, that in the judgment of the Investigator or Sponsor, may increase the risk associated with study participation or investigational product administration, or may interfere with the interpretation of study results, and would make the participant inappropriate for entry into this study * Subjects who are treatment naive Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Rescue Event During the DB Period | Baseline to Week 26 for participants continuing to OLE and up to Week 30 for participants not continuing to OLE, as rescue events occurring within 8 weeks of last dose were included in the analysis for participants not continuing to the OLE period. | Rescue events included: Participants with worsening sarcoidosis requiring rescue treatment; and participants failing to follow protocol defined concomitant sarcoidosis medication requirements (oral corticosteroids \[OCS\] taper/immunosuppressive therapy \[IST\] removal/prohibited medication). Participants with premature treatment discontinuation in the DB period without rescue event were considered as with missing rescue event status and excluded from analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 26 | Baseline, Week 26 | FVC is the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. Percent of predicted FVC = (actual FVC measurement)/(predicted value of FVC) \* 100. Least square (LS) mean and standard error (SE) were calculated using mixed model for repeated measure (MMRM). |
| Time to the First Rescue Event During the DB Period | Baseline to Week 26 for participants continuing to OLE and up to Week 30 for participants not continuing to OLE, as rescue events occurring within 8 weeks of last dose were included in the analysis for participants not continuing to the OLE period. | Time of first rescue event was defined as the time from randomization to the rescue event date. Rescue events included: Participants with worsening sarcoidosis requiring rescue treatment; and participants failing to follow protocol defined concomitant sarcoidosis medication requirements (OCS taper/IST removal/prohibited medication). Data was calculated using the Kaplan-Meier estimator. |
| Percentage of Participants Successfully Achieving OCS Taper Without Rescue Event During the DB Period | Baseline to Week 26 | Percentage of participants achieving OCS taper (achieving OCS dose ≤5 milligrams \[mg\] at end of Week 10 \[Day 77\] for participants with baseline OCS \>10 mg/day, achieving ≤ 5 mg at end of Week 6 \[Day 49\] for participants with baseline OCS \>5 to ≤10 mg/day) without any rescue event during the DB period for participants with OCS \>5 mg/day at baseline are reported. |
| Change From Baseline in the Kings Sarcoidosis Questionnaire (KSQ) Lung Domain Score at Week 26 | Baseline, Week 26 | The KSQ has 29 questions (items 1 to 16, and items 26-38). The KSQ Lung domain score was calculated based on items 11 to 16. Each item was answered on a 7-point scale where 1 means the participant experienced symptoms all the time and 7 means the participant did not experience the symptom at all. The raw item scores were first converted into item re-scores using the first conversion step. Then, the re-scores for the 6 items were totaled and the total converted into the logit 1 (worst symptom) - 100 (no symptom) score, where higher score indicating better health. LS mean and SE were calculated using MMRM. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the DB Period | Baseline up to Week 26 | An adverse event (AE) was any untoward medical occurrence in a participant administered the study drug and which did not necessarily have a causal relationship with this treatment. TEAEs are those AEs with start date on or after the start date of treatment through the earlier of 18-week post last dose during DB period or prior to first dose during OLE period, whichever was earlier. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
Countries
Belgium, France, Germany, Netherlands, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
The study included a double-blind (DB) period and an open-label extension (OLE) period.
Participants by arm
| Arm | Count |
|---|---|
| Namilumab Participants received namilumab SC on Day 1, Day 15 (Week 2), and then Q4W thereafter through Week 22. | 52 |
| Placebo Participants received placebo matched to namilumab dosing through Week 22. | 54 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-blind Period | Adverse Event | 4 | 0 | 0 | 0 |
| Double-blind Period | Noncompliance | 0 | 1 | 0 | 0 |
| Double-blind Period | Randomized, not treated | 1 | 0 | 0 | 0 |
| Open-label Extension | Adverse Event | 0 | 0 | 1 | 2 |
| Open-label Extension | Investigator decision | 0 | 0 | 1 | 0 |
| Open-label Extension | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Open-label Extension | Sponsor decision to terminate study | 0 | 0 | 13 | 15 |
| Open-label Extension | Use of prohibited medication | 0 | 0 | 1 | 0 |
| Open-label Extension | Withdrawal by Subject | 0 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | Namilumab |
|---|---|---|---|
| Age, Continuous | 54.1 years STANDARD_DEVIATION 10.35 | 52.9 years STANDARD_DEVIATION 11.27 | 51.7 years STANDARD_DEVIATION 12.13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants | 99 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 10 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 8 Participants | 3 Participants |
| Race (NIH/OMB) White | 45 Participants | 88 Participants | 43 Participants |
| Sex: Female, Male Female | 22 Participants | 45 Participants | 23 Participants |
| Sex: Female, Male Male | 32 Participants | 61 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 54 | 0 / 52 | 0 / 49 |
| other Total, other adverse events | 49 / 52 | 51 / 54 | 51 / 52 | 44 / 49 |
| serious Total, serious adverse events | 3 / 52 | 3 / 54 | 7 / 52 | 5 / 49 |
Outcome results
Primary
Percentage of Participants With a Rescue Event During the DB Period
Rescue events included: Participants with worsening sarcoidosis requiring rescue treatment; and participants failing to follow protocol defined concomitant sarcoidosis medication requirements (oral corticosteroids \[OCS\] taper/immunosuppressive therapy \[IST\] removal/prohibited medication). Participants with premature treatment discontinuation in the DB period without rescue event were considered as with missing rescue event status and excluded from analysis.
Time frame: Baseline to Week 26 for participants continuing to OLE and up to Week 30 for participants not continuing to OLE, as rescue events occurring within 8 weeks of last dose were included in the analysis for participants not continuing to the OLE period.
Population: mITT population included all randomized participants who received any amount of DB study treatment, excluding participants with a quality event. 'Overall number of participants analyzed' = participants with rescue event status.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Namilumab | Percentage of Participants With a Rescue Event During the DB Period | 37.5 percentage of participants |
| Placebo | Percentage of Participants With a Rescue Event During the DB Period | 23.5 percentage of participants |
p-value: 0.124490% CI: [-1, 29.2]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 26
FVC is the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. Percent of predicted FVC = (actual FVC measurement)/(predicted value of FVC) \* 100. Least square (LS) mean and standard error (SE) were calculated using mixed model for repeated measure (MMRM).
Time frame: Baseline, Week 26
Population: The mITT population included all randomized participants who received any amount of DB study treatment, excluding participants with a quality event. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Namilumab | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 26 | -3.28 percentage of predicted FVC | Standard Error 1.058 |
| Placebo | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 26 | -2.92 percentage of predicted FVC | Standard Error 0.967 |
Secondary
Change From Baseline in the Kings Sarcoidosis Questionnaire (KSQ) Lung Domain Score at Week 26
The KSQ has 29 questions (items 1 to 16, and items 26-38). The KSQ Lung domain score was calculated based on items 11 to 16. Each item was answered on a 7-point scale where 1 means the participant experienced symptoms all the time and 7 means the participant did not experience the symptom at all. The raw item scores were first converted into item re-scores using the first conversion step. Then, the re-scores for the 6 items were totaled and the total converted into the logit 1 (worst symptom) - 100 (no symptom) score, where higher score indicating better health. LS mean and SE were calculated using MMRM.
Time frame: Baseline, Week 26
Population: The mITT population included all randomized participants who received any amount of DB study treatment, excluding participants with a quality event. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Namilumab | Change From Baseline in the Kings Sarcoidosis Questionnaire (KSQ) Lung Domain Score at Week 26 | 1.61 units on a scale | Standard Error 1.866 |
| Placebo | Change From Baseline in the Kings Sarcoidosis Questionnaire (KSQ) Lung Domain Score at Week 26 | 3.47 units on a scale | Standard Error 1.771 |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the DB Period
An adverse event (AE) was any untoward medical occurrence in a participant administered the study drug and which did not necessarily have a causal relationship with this treatment. TEAEs are those AEs with start date on or after the start date of treatment through the earlier of 18-week post last dose during DB period or prior to first dose during OLE period, whichever was earlier. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time frame: Baseline up to Week 26
Population: Safety population included all randomized participants who received any amount of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Namilumab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the DB Period | 49 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the DB Period | 51 Participants |
Secondary
Percentage of Participants Successfully Achieving OCS Taper Without Rescue Event During the DB Period
Percentage of participants achieving OCS taper (achieving OCS dose ≤5 milligrams \[mg\] at end of Week 10 \[Day 77\] for participants with baseline OCS \>10 mg/day, achieving ≤ 5 mg at end of Week 6 \[Day 49\] for participants with baseline OCS \>5 to ≤10 mg/day) without any rescue event during the DB period for participants with OCS \>5 mg/day at baseline are reported.
Time frame: Baseline to Week 26
Population: The mITT population included all randomized participants who received any amount of DB study treatment, excluding participants with a quality event. 'Overall number of participants analyzed' = participants with OCS \>5 mg/day at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Namilumab | Percentage of Participants Successfully Achieving OCS Taper Without Rescue Event During the DB Period | 53.3 percentage of participants |
| Placebo | Percentage of Participants Successfully Achieving OCS Taper Without Rescue Event During the DB Period | 76.9 percentage of participants |
Secondary
Time to the First Rescue Event During the DB Period
Time of first rescue event was defined as the time from randomization to the rescue event date. Rescue events included: Participants with worsening sarcoidosis requiring rescue treatment; and participants failing to follow protocol defined concomitant sarcoidosis medication requirements (OCS taper/IST removal/prohibited medication). Data was calculated using the Kaplan-Meier estimator.
Time frame: Baseline to Week 26 for participants continuing to OLE and up to Week 30 for participants not continuing to OLE, as rescue events occurring within 8 weeks of last dose were included in the analysis for participants not continuing to the OLE period.
Population: mITT population included all randomized participants who received any amount of DB study treatment, excluding participants with a quality event.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Namilumab | Time to the First Rescue Event During the DB Period | 11.0 weeks |
| Placebo | Time to the First Rescue Event During the DB Period | 12.86 weeks |