Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

The VOLTAIRE-X Trial Looks at the Effect of Switching Between Humira® and BI 695501 in Patients With Plaque Psoriasis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03210259
Recruitment Status : Completed
First Posted : July 6, 2017
Results First Posted : July 2, 2021
Last Update Posted : July 14, 2021
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Psoriasis
Interventions Drug: Humira®
Drug: BI 695501
Enrollment 259
Recruitment Details This was a 58-week, multiple-dose, active comparator trial of BI 695501 and US-licensed Humira in patients with moderate to severe chronic plaque psoriasis. The trial consisted of a single-arm run-in period of 14 weeks for all patients, followed by a randomized, double-blind, 2-arm period of 34 weeks. The total treatment period was 48 weeks followed by 10 weeks of safety follow up (SFU).
Pre-assignment Details

All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria.

Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Arm/Group Title Not Randomized Switching Arm (Post-Randomization Period) Continuous Humira (Post-Randomization Period)
Hide Arm/Group Description

Patients received US-licensed Humira during the run-in period. A loading dose of 80 milligrams (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. At the beginning of Week 14, patients who achieved at least a 50 percent reduction in Psoriasis Area and Severity Index (PASI50) response were randomized in a 1:1 ratio to either a continuous arm receiving 40mg of US-licensed Humira every other week until week 48 or in a switching arm separated in 3 periods.

Patients who participated in the run-in period but not being randomized after run-in period were included in this group.

Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up.

During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the switching arm were included in this group.

Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.

Period Title: 12-Week Run-in Period
Started [1] 21 118 120
Completed [2] 0 118 120
Not Completed 21 0 0
Reason Not Completed
Adverse Event             1             0             0
Death             1             0             0
Withdrawal by Subject             9             0             0
Lost to Follow-up             4             0             0
Lack of Efficacy             6             0             0
[1]
Enrolled
[2]
Completed the run-in period
Period Title: 48-Week Randomized Responder Period
Started [1] 0 118 120
Completed [2] 0 107 91
Not Completed 0 11 29
Reason Not Completed
Missed study visit             0             1             2
Lost to Follow-up             0             3             8
Pregnancy             0             1             0
Physician Decision             0             0             1
Withdrawal by Subject             0             5             17
Adverse Event             0             1             1
[1]
Randomization
[2]
Completed the trial
Arm/Group Title Switching Arm (Post-Randomization Period) Continuous Humira (Post-Randomization Period) Total
Hide Arm/Group Description

Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up.

During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the switching arm were included in this group.

Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.

Total of all reporting groups
Overall Number of Baseline Participants 118 120 238
Hide Baseline Analysis Population Description
Treated Set (TS) contained all randomized patients who received at least 1 dose of trial medication administered in the post-randomization period.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 118 participants 120 participants 238 participants
46.1  (13.95) 43.7  (13.69) 44.9  (13.84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 118 participants 120 participants 238 participants
Female
37
  31.4%
44
  36.7%
81
  34.0%
Male
81
  68.6%
76
  63.3%
157
  66.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 118 participants 120 participants 238 participants
Hispanic or Latino
18
  15.3%
18
  15.0%
36
  15.1%
Not Hispanic or Latino
100
  84.7%
102
  85.0%
202
  84.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 118 participants 120 participants 238 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   1.7%
0
   0.0%
2
   0.8%
Native Hawaiian or Other Pacific Islander
1
   0.8%
0
   0.0%
1
   0.4%
Black or African American
2
   1.7%
0
   0.0%
2
   0.8%
White
113
  95.8%
119
  99.2%
232
  97.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
1
   0.8%
1
   0.4%
1.Primary Outcome
Title Area Under the Plasma Concentration Time Curve Over the Dosing Interval of Week 30 to 32 (AUCτ, 30-32) for Adalimumab in Plasma
Hide Description Area Under the Plasma Concentration Time Curve Over the 2 weeks dosing Interval between Week 30 to 32 (AUCτ, 30-32) for Adalimumab in plasma was reported.
Time Frame Pre-dose at Week 30, at 72, 120, 168 and 240 hours after the Week 30 dosing, and pre-dose at Week 32.
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic (PK) Set (PKS) included all patients from the TS who provided at least 1 primary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK.
Arm/Group Title Switching Arm (Post-Randomization Period) Continuous Humira (Post-Randomization Period)
Hide Arm/Group Description:

Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up.

During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the switching arm were included in this group.

Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.

Overall Number of Participants Analyzed 102 93
Mean (Standard Deviation)
Unit of Measure: microgram * hours / milliliter
2040  (1420) 1980  (1600)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Switching Arm (Post-Randomization Period), Continuous Humira (Post-Randomization Period)
Comments The null hypothesis was that the ratio of expected means for Switching vs. Continuous Humira is less than 80.00% or more than 125.00%.
Type of Statistical Test Equivalence
Comments Equivalence was concluded if the confidence interval (CI) for the least squares (LS) means ratio was included in the pre-defined equivalence range of 80.00% to 125.00%.
Method of Estimation Estimation Parameter Least squares means ratio
Estimated Value 105.19
Confidence Interval (2-Sided) 90.2%
96.58 to 114.64
Estimation Comments The least squares means were from ANCOVA. Ratio was calculated with the switching arm in the numerator and the continuous arm in the denominator.
2.Primary Outcome
Title Maximum Observed Concentration During the Dosing Interval Week 30-32 (Cmax, 30-32) for Adalimumab in Plasma
Hide Description Maximum observed concentration during the 2 weeks dosing interval between Week 30 to 32 (Cmax, 30-32) for Adalimumab in plasma was reported.
Time Frame Pre-dose at Week 30, at 72, 120, 168 and 240 hours after the Week 30 dosing, and pre-dose at Week 32.
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Set (PKS) included all patients from the TS who provided at least 1 primary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK.
Arm/Group Title Switching Arm (Post-Randomization Period) Continuous Humira (Post-Randomization Period)
Hide Arm/Group Description:

Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up.

During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the switching arm were included in this group.

Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.

Overall Number of Participants Analyzed 104 99
Mean (Standard Deviation)
Unit of Measure: microgram / milliliter
7.13  (4.63) 7.14  (5.37)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Switching Arm (Post-Randomization Period), Continuous Humira (Post-Randomization Period)
Comments The null hypothesis was that the ratio of expected means for Switching vs. Continuous Humira is less than 80.00% or more than 125.00%.
Type of Statistical Test Equivalence
Comments Equivalence was concluded if the confidence interval (CI) for the LS means ratio was included in the pre-defined equivalence range of 80.00% to 125.00%.
Method of Estimation Estimation Parameter Least squares means ratio
Estimated Value 101.14
Confidence Interval (2-Sided) 90.2%
93.26 to 109.70
Estimation Comments The least squares means were from ANCOVA. Ratio was calculated with the switching arm in the numerator and the continuous arm in the denominator.
3.Secondary Outcome
Title Minimum Observed Concentration During the Dosing Interval of Week 30 to 32 (Cmin, 30-32) for Adalimumab in Plasma
Hide Description Minimum Observed Concentration During the 2 weeks Dosing Interval between Week 30 to 32 (Cmin, 30-32) for Adalimumab in plasma was reported.
Time Frame Pre-dose at Week 30, at 72, 120, 168 and 240 hours after the Week 30 dosing, and pre-dose at Week 32.
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Set (PKS) included all patients from the TS who provided at least 1 primary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK.
Arm/Group Title Switching Arm (Post-Randomization Period) Continuous Humira (Post-Randomization Period)
Hide Arm/Group Description:

Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up.

During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the switching arm were included in this group.

Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.

Overall Number of Participants Analyzed 104 98
Mean (Standard Deviation)
Unit of Measure: micogram / milliliter
5.04  (3.89) 4.66  (4.19)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Switching Arm (Post-Randomization Period), Continuous Humira (Post-Randomization Period)
Comments No hypothesis was defined and no statistical test was performed.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares means ratio
Estimated Value 107.31
Confidence Interval (2-Sided) 90.2%
97.33 to 118.43
Estimation Comments The least squares means were from ANCOVA. Ratio was calculated with the switching arm as numerator and the continuous arm as the denominator.
4.Secondary Outcome
Title Time to Maximum Observed Concentration During the Dosing Interval of Week 30 to 32 (Tmax, 30-32) for Adalimumab in Plasma
Hide Description Time to Maximum Observed Concentration During the 2 weeks Dosing Interval between Week 30 to 32 (tmax, 30-32) for Adalimumab in plasma was reported.
Time Frame Pre-dose at Week 30, at 72, 120, 168 and 240 hours after the Week 30 dosing, and pre-dose at Week 32.
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Set (PKS) included all patients from the TS who provided at least 1 primary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK.
Arm/Group Title Switching Arm (Post-Randomization Period) Continuous Humira (Post-Randomization Period)
Hide Arm/Group Description:

Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up.

During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the switching arm were included in this group.

Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.

Overall Number of Participants Analyzed 104 99
Median (Full Range)
Unit of Measure: hours
72.7
(66.0 to 336)
72.3
(46.8 to 240)
5.Secondary Outcome
Title Percentage of Patients With a 75% Reduction in Psoriasis Area and Severity Index (PASI75) Response at Week 32
Hide Description The PASI is an established measure of clinical efficacy for psoriasis medications. The PASI is a tool which provides a numeric scoring for patients' overall psoriasis disease state, with scores ranging from 0 to 72. It is a linear combination of percent of surface area of skin that is affected and the severity of erythema, induration, and desquamation over four body regions (head, trunk, upper extremities and lower extremities). Higher PASI scores indicate more severe psoriasis. PASI is generally summarized as a dichotomous outcome based on achieving over an X percent(%) reduction from baseline (or PASIX), where X is 50, 75, 90, and 100. Results are reported for percentage of patients with a PASI75 response at Week 32. Analysis was done on per-protocol analysis set (PPS).
Time Frame At week 32
Hide Outcome Measure Data
Hide Analysis Population Description
The PPS contained all patients from the TS who did not experience any important protocol violations relevant for efficacy. Missing data were imputed via non-responder imputation for patients who discontinued treatment early and multiple imputation (MI) for missing at random value. There were no cases where it was required to implement MI.
Arm/Group Title Switching Arm (Post-Randomization Period) Continuous Humira (Post-Randomization Period)
Hide Arm/Group Description:

Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up.

During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the switching arm were included in this group.

Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.

Overall Number of Participants Analyzed 118 119
Measure Type: Number
Unit of Measure: Percentage of patients
84.75 78.99
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Switching Arm (Post-Randomization Period), Continuous Humira (Post-Randomization Period)
Comments No hypothesis was tested.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 5.75
Confidence Interval (2-Sided) 90%
-2.45 to 13.96
Estimation Comments Risk difference was calculated as Switching arm minus Continuous Humira.
6.Secondary Outcome
Title Percentage of Patients With a Static Physician's Global Assessment (sPGA) Score ≤ 1 (Clear or Almost Clear) at Week 32
Hide Description The sPGA is a 5-point score ranging from 0 to 4, based on the physician's assessment of the average thickness, erythema, and scaling of all psoriatic lesions. The assessment is considered "static", which refers to the patient's disease state at the time of the assessments, without comparison to any of the patient's previous disease states (dynamic), whether at baseline or at a previous visit. A lower score indicates less body coverage and a higher score indicates more severe disease (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe). Results are reported for percentage of patients with a sPGA score of ≤ 1 (clear or almost clear) at Week 32. Analysis was done on per-protocol analysis set (PPS).
Time Frame At week 32
Hide Outcome Measure Data
Hide Analysis Population Description
The PPS contained all patients from the TS who did not experience any important protocol violations relevant for efficacy. Missing data were imputed via non-responder imputation for patients who discontinued treatment early and multiple imputation (MI) for missing at random value. There were no cases where it was required to implement MI.
Arm/Group Title Switching Arm (Post-Randomization Period) Continuous Humira (Post-Randomization Period)
Hide Arm/Group Description:

Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up.

During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the switching arm were included in this group.

Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.

Overall Number of Participants Analyzed 118 119
Measure Type: Number
Unit of Measure: Percentage of patients
70.34 64.71
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Switching Arm (Post-Randomization Period), Continuous Humira (Post-Randomization Period)
Comments No hypothesis was tested.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 5.63
Confidence Interval (2-Sided) 90%
-4.35 to 15.62
Estimation Comments Risk difference was calculated as Switching arm minus Continuous Humira.
7.Secondary Outcome
Title Number of Patients With Anti-drug Antibody (ADA) to Adalimumab at Week 32
Hide Description Number of patients with a confirmed positive anti-drug antibody (ADA) response to Adalimumab (BI 695501 or Humira) at Week 32. A participant was considered "ADA positive" if the blank normalized signal in the ADA screening assay was equal to or above the study specific ADA screening cut point factor of 1.06 and the signal inhibition by drug in the ADA confirmatory assay was equal to or above the study specific ADA confirmatory cut points (11.4% for signal inhibition with Humira and 12.0% for signal inhibition with BI 695501).
Time Frame Immunogenicity samples were collected pre-dose at Week 32.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients in the TS who had non-missing endpoints. The TS contained all randomized patients who received at least 1 dose of trial medication administered in the post-randomization period.
Arm/Group Title Switching Arm (Post-Randomization Period) Continuous Humira (Post-Randomization Period)
Hide Arm/Group Description:

Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up.

During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the switching arm were included in this group.

Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.

Overall Number of Participants Analyzed 112 112
Measure Type: Count of Participants
Unit of Measure: Participants
Negative
11
   9.8%
6
   5.4%
Positive
101
  90.2%
104
  92.9%
Total reportable
112
 100.0%
110
  98.2%
Not reportable
0
   0.0%
2
   1.8%
8.Secondary Outcome
Title Number of Patients With Neutralizing Antibody (nAb) to Adalimumab at Week 32
Hide Description Number of patients with a positive neutralizing anti-drug antibody (nAb) response to Adalimumab (BI 695501 or Humira) at Week 32. A participant was considered "nAb positive" if the blank normalized signal in the nAb screening assay was equal to or below the study specific nAb screening cut point factor of 0.836.
Time Frame Immunogenicity samples were collected pre-dose at Week 32.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients in the TS who had non-missing endpoints. The TS contained all randomized patients who received at least 1 dose of trial medication administered in the post-randomization period.
Arm/Group Title Switching Arm (Post-Randomization Period) Continuous Humira (Post-Randomization Period)
Hide Arm/Group Description:

Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up.

During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the switching arm were included in this group.

Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.

Overall Number of Participants Analyzed 112 112
Measure Type: Count of Participants
Unit of Measure: Participants
Negative
66
  58.9%
64
  57.1%
Positive
46
  41.1%
46
  41.1%
Total reportable
112
 100.0%
110
  98.2%
Not reportable
0
   0.0%
2
   1.8%
9.Secondary Outcome
Title Anti-drug Antibody (ADA) Titer of Patients With ADA at Week 32
Hide Description Anti-drug antibody (ADA) titer of patients with a confirmed positive ADA response to Adalimumab (BI 695501 or Humira) at Week 32.
Time Frame Immunogenicity samples were collected pre-dose at Week 32.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was on patients in the treated set (TS) with positive ADA at week 32. The TS contained all randomized patients who received at least 1 dose of trial medication administered in the post-randomization period.
Arm/Group Title Switching Arm (Post-Randomization Period) Continuous Humira (Post-Randomization Period)
Hide Arm/Group Description:

Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up.

During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the switching arm were included in this group.

Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.

Overall Number of Participants Analyzed 101 104
Median (Inter-Quartile Range)
Unit of Measure: Titer
64.0
(32.00 to 256.00)
128
(16.00 to 256.00)
10.Secondary Outcome
Title Neutralizing Anti-drug Antibody (nAb) Titer of Patients With nAb at Week 32
Hide Description Neutralizing anti-drug antibody (nAb) titer of patients with a positive nAb response to Adalimumab (BI 695501 or Humira) at Week 32.
Time Frame Immunogenicity samples were collected pre-dose at Week 32.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was on patients in the treated set (TS) with positive nAb at week 32. The TS contained all randomized patients who received at least 1 dose of trial medication administered in the post-randomization period.
Arm/Group Title Switching Arm (Post-Randomization Period) Continuous Humira (Post-Randomization Period)
Hide Arm/Group Description:

Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up.

During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the switching arm were included in this group.

Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.

Overall Number of Participants Analyzed 46 46
Median (Inter-Quartile Range)
Unit of Measure: Titer
2.0
(1.00 to 4.00)
2.0
(1.00 to 2.00)
11.Secondary Outcome
Title Percentage of Patients With Drug-related Adverse Events (AEs) During the Post-Randomization Period
Hide Description Analysis of AEs focused on treatment-emergent adverse events (TEAEs) and is presented here for the post-randomization period (Week 14 to 58). For the post-randomization period analysis, TEAEs were defined as AEs that started or worsened on or after the first dose of trial post-randomization medication and prior to the last dose of trial post-randomization medication + 10 weeks.
Time Frame From first dose of trial post-randomization medication until 10 weeks after last dose of trial post-randomization medication, up to 44 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The Treated Set (TS) contained all randomized patients who received at least 1 dose of trial medication administered in the post-randomization period.
Arm/Group Title Switching Arm (Post-Randomization Period) Continuous Humira (Post-Randomization Period)
Hide Arm/Group Description:

Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up.

During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the switching arm were included in this group.

Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.

Overall Number of Participants Analyzed 118 120
Measure Type: Number
Unit of Measure: Percentage of patients
11.9 18.3
Time Frame From first post-randomized trial medication until 10 weeks after last dose, up to 44 weeks (Post-Randomization Period). From first dose of Humira and prior to the first dose of post-randomization medication+10 weeks, up to 24 weeks (Run-In Period).
Adverse Event Reporting Description Safety analyses were performed based on the Treated Set (TS) and Run-in Treated Set (RTS). The TS contained all randomized patients who received at least 1 dose of trial medication administered in the post-randomization period. The RTS contained all enrolled patients treated with at least 1 dose of US-licensed Humira during the run-in period.
 
Arm/Group Title Humira Containing All RTS Subjects (Run-In Period) Switching Arm (Post-Randomization Period) Continuous Humira (Post-Randomization Period)
Hide Arm/Group Description

All patients received US-licensed Humira during the run-in period of 14 weeks (Period 1). Patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL).

All patients in the run-in period were in this group including those who were randomised and who did not being randomised after the run-in period.

Patients initially received US-licensed Humira during the run-in period (Period 1) of 14 weeks and were then randomized to the switching arm for the randomized treatment period (Period 2) of 34 weeks followed by 10 weeks of safety follow-up.

During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg BI 695501 at Week 14 and Week 16 (2 injections), followed by 40 mg US-licensed Humira at Week 18 and Week 20 (2 injections), and subsequently 40 mg BI 695501 every other week from Week 22 to Week 48 (14 injections). Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab or BI 695501 per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the switching arm were included in this group.

Patients initially received US-licensed Humira during the run-in period of 14 weeks (Period 1) and were then randomized to the continuous Humira arm for the randomized treatment period of 34 weeks (Period 2) followed by 10 weeks of safety follow-up. During Period 1, patients were administered with a loading dose of 80 milligram (mg) US-licensed Humira on Day 1 (Week 1), followed by 40 mg every other week from Week 2 to Week 12. During Period 2, patients received 40 mg US-licensed Humira every other week from Week 14 to Week 48 (18 injections).Trial medication were administered by subcutaneous (s.c.) injection providing in single-use pre-filled syringes (PFS) containing 40 mg of adalimumab per 0.8 milliliter (mL).

Patients who went through the run-in period and being randomised into the continuous Humira arm were included in this group.

All-Cause Mortality
Humira Containing All RTS Subjects (Run-In Period) Switching Arm (Post-Randomization Period) Continuous Humira (Post-Randomization Period)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/259 (0.39%)   0/118 (0.00%)   0/120 (0.00%) 
Hide Serious Adverse Events
Humira Containing All RTS Subjects (Run-In Period) Switching Arm (Post-Randomization Period) Continuous Humira (Post-Randomization Period)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/259 (2.32%)   5/118 (4.24%)   4/120 (3.33%) 
Blood and lymphatic system disorders       
Leukocytosis  1  1/259 (0.39%)  0/118 (0.00%)  0/120 (0.00%) 
Microcytic anaemia  1  0/259 (0.00%)  1/118 (0.85%)  0/120 (0.00%) 
Cardiac disorders       
Acute myocardial infarction  1  0/259 (0.00%)  0/118 (0.00%)  1/120 (0.83%) 
Atrial fibrillation  1  1/259 (0.39%)  0/118 (0.00%)  0/120 (0.00%) 
Sinus arrest  1  0/259 (0.00%)  0/118 (0.00%)  1/120 (0.83%) 
Gastrointestinal disorders       
Abdominal pain  1  0/259 (0.00%)  1/118 (0.85%)  0/120 (0.00%) 
Pancreatitis acute  1  1/259 (0.39%)  0/118 (0.00%)  0/120 (0.00%) 
General disorders       
Death  1  1/259 (0.39%)  0/118 (0.00%)  0/120 (0.00%) 
Infections and infestations       
Gastroenteritis  1  0/259 (0.00%)  1/118 (0.85%)  0/120 (0.00%) 
Influenza  1  0/259 (0.00%)  1/118 (0.85%)  0/120 (0.00%) 
Pneumonia chlamydial  1  0/259 (0.00%)  0/118 (0.00%)  1/120 (0.83%) 
Injury, poisoning and procedural complications       
Diffuse axonal injury  1  1/259 (0.39%)  0/118 (0.00%)  0/120 (0.00%) 
Joint dislocation  1  0/259 (0.00%)  1/118 (0.85%)  0/120 (0.00%) 
Ligament rupture  1  0/259 (0.00%)  0/118 (0.00%)  1/120 (0.83%) 
Thermal burn  1  1/259 (0.39%)  0/118 (0.00%)  0/120 (0.00%) 
Investigations       
Alanine aminotransferase increased  1  0/259 (0.00%)  1/118 (0.85%)  0/120 (0.00%) 
Aspartate aminotransferase increased  1  0/259 (0.00%)  1/118 (0.85%)  0/120 (0.00%) 
Musculoskeletal and connective tissue disorders       
Psoriatic arthropathy  1  1/259 (0.39%)  0/118 (0.00%)  0/120 (0.00%) 
Nervous system disorders       
Demyelination  1  1/259 (0.39%)  0/118 (0.00%)  0/120 (0.00%) 
Skin and subcutaneous tissue disorders       
Psoriasis  1  1/259 (0.39%)  0/118 (0.00%)  0/120 (0.00%) 
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Humira Containing All RTS Subjects (Run-In Period) Switching Arm (Post-Randomization Period) Continuous Humira (Post-Randomization Period)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   24/259 (9.27%)   17/118 (14.41%)   11/120 (9.17%) 
Infections and infestations       
Nasopharyngitis  1  16/259 (6.18%)  11/118 (9.32%)  5/120 (4.17%) 
Nervous system disorders       
Headache  1  10/259 (3.86%)  6/118 (5.08%)  6/120 (5.00%) 
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results.

Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days.

BI may request a delay of the publication in order to protect BI's intellectual property rights.

Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT03210259    
Other Study ID Numbers: 1297-0009
2016-002254-20 ( EudraCT Number )
First Submitted: July 5, 2017
First Posted: July 6, 2017
Results First Submitted: April 26, 2021
Results First Posted: July 2, 2021
Last Update Posted: July 14, 2021