Safety and Efficacy Study of RA101495 in Subjects With Generalized Myasthenia Gravis
Sponsor
Ra Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT03315130
Collaborator
(none)
45
30
3
37.3
1.5
0
Study Details
Study Description
Brief Summary
The purpose of the study is to evaluate the safety and efficacy of RA101495 in patients with generalized Myasthenia Gravis (gMG). Subjects will be randomized in a 1:1:1 ratio to receive daily SC doses of 0.1 mg/kg RA101495, 0.3 mg/kg RA101495, or matching placebo for 12 weeks.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
45 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of RA101495 in Subjects With Generalized Myasthenia Gravis
Actual Study Start Date
:
Oct 11, 2017
Actual Primary Completion Date
:
Dec 10, 2018
Actual Study Completion Date
:
Nov 19, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 0.1 mg/kg zilucoplan (RA101495)
|
Drug: zilucoplan (RA101495)
Daily subcutaneous (SC) injection
|
| Experimental: 0.3 mg/kg zilucoplan (RA101495)
|
Drug: zilucoplan (RA101495)
Daily subcutaneous (SC) injection
|
| Placebo Comparator: Placebo
|
Drug: Placebo
Daily subcutaneous (SC) injection
|
Outcome Measures
Primary Outcome Measures
- Main Portion: Change From Baseline to Week 12 in Quantitative Myasthenia Gravis (QMG) Score [From Baseline to Week 12]
The QMG is a standardized and validated quantitative strength scoring system that was developed specifically for myasthenia gravis (MG). The scale consists of 13 individual assessments, each scored on a 0-3 point scale (i.e., 0=none, 1=mild, 2=moderate, and 3=severe). The total score is the sum of the individual scores with a range of 0-39. Higher scores are representative of more severe impairment.
Secondary Outcome Measures
- Main Portion: Change From Baseline to Week 12 in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) Scale [From Baseline to Week 12]
The MG-ADL is a brief 8-item survey designed to evaluate MG symptom severity. The scale consists of 8 items each scored on a 0-3 point scale (i.e., 0=none, 1=mild, 2=moderate, and 3=severe). The total score is the sum of the 8 individual scores with range of 0-24. Higher scores are associated with more severe symptoms of MG.
- Main Portion: Change From Baseline to Week 12 in the Myasthenia Gravis - Quality of Life 15r (MG-QOL15r) Survey [From Baseline to Week 12]
The MG-QOL15r is a 15-item survey that was designed to assess quality of life in participants with MG. The survey consisted of 15 questions and the corresponding responses were each scored on a 0-2 point scale (0=Not much at all, 1=Somewhat, 2=Very Much). The total score is the sum of the 15 individual item scores with a range of 0-30. Higher scores indicate more severe impact of the disease on aspects of the participant's life.
- Main Portion: Change From Baseline to Week 12 in the MG Composite Scale Total Score [From Baseline to Week 12]
The MG Composite is a 10-item scale that has been used to measure the clinical status of participants with MG, in order to evaluate treatment response. It consists of 10 items which included ptosis (score range=0 to 3), double vision on lateral gaze left/right/both (score range=0 to 4), eye closure (score range=0 to 2), talking (score range=0 to 6), chewing (score range=0 to 6), swallowing (score range=0 to 6), breathing (score range=0 to 9), neck flexion or extension (score range=0 to 4), shoulder abduction (score range=0 to 5) and hip flexion (score range= 0 to 5). The total score is the sum of the 10 individual scores with a range of 0-50. Higher scores in the MG Composite indicate more severe impairment due to the disease.
- Main Portion: Percentage of Participants With >= 3-point Reduction in QMG Total Score at Week 12 [Week 12]
The QMG is a standardized and validated quantitative strength scoring system that was developed specifically for MG. The scale consists of 13 individual assessments, each scored on a 0-3 point scale (i.e., 0=none, 1=mild, 2=moderate, and 3=severe). The total score is the sum of the individual scores with a range of 0-39. Higher scores are representative of more severe impairment.
- Main Portion: Percentage of Participants Who Required Rescue Therapy Over the 12-week Treatment Period [Up to Week 12]
Percentage of participants who used at least 1 dose of rescue medication were reported.
- Main Portion: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [From Baseline to Week 12]
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A serious adverse event (SAE) is any untoward medical occurrence that at any dose resulted in death, life-threatening, significant or persistent disability/incapacity, congenital anomaly/birth defect, important medical event, initial inpatient hospitalization or prolongation of hospitalization.
- Main Portion: Change From Baseline in Sheep Red Blood Cell (sRBC) Lysis Assay at Week 12 (Pre-dose) [Baseline and Week 12 (Pre-dose)]
A BioTek ELx800 automated microplate reader is used to measure the optical density at 415 nanometer (nm) of human plasma samples to calculate the percent lysis of sheep erythrocytes that has occurred as a result of total complement activity. The measure of complement activity is determined by the degree of hemolysis of the erythrocytes.
- Main Portion: Change From Baseline in C5 Levels at Week 12 (Pre-dose) [Baseline and Week 12 (Pre-dose)]
Blood samples were collected from participants to assess Complement Component 5C levels.
- Main Portion: Plasma Concentration of RA101495 and Its Major Metabolites [1, 3 and 6 hours postdose on Day 1; Pre-dose on Week 1, 2, 4, 8 and 12]
RA102758 and RA103488 are the metabolites of RA101495.
- Main Portion: Maximum Plasma Concentration (Cmax) on Day 1 [Pre-dose, 1, 3 and 6 hours postdose on Day 1]
Cmax is defined as the maximum observed plasma concentration.
- Main Portion: Time Corresponding to Cmax (Tmax) on Day 1 [Pre-dose, 1, 3 and 6 hours postdose on Day 1]
Tmax is defined as the time to observe maximum plasma concentration.
- Main Portion: Metabolites (RA102758 and RA103488) to Parent Ratio [Pre-dose, 1, 3 and 6 hours postdose on Day 1; Pre-dose on Week 1, 2, 4, 8 and 12]
RA102758 and RA103488 are the metabolites of RA101495.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 85 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Diagnosis of gMG [Myasthenia Gravis Foundation of America (MGFA) Class II-IVa] at Screening
-
Positive serology for acetylcholine receptor (AChR) autoantibodies
-
QMG score ≥ 12 at Screening and Randomization
-
No change in corticosteroid dose for at least 30 days prior to Randomization or anticipated to occur during the 12-week Treatment Period
-
No change in immunosuppressive therapy, including dose, for at least 30 days prior to Randomization or anticipated to occur during the 12-week Treatment Period
Exclusion Criteria:
-
Thymectomy within 6 months prior to Randomization or scheduled to occur during the 12 week Treatment Period
-
History of meningococcal disease
-
Current or recent systemic infection within 2 weeks prior to Randomization or infection requiring intravenous (IV) antibiotics within 4 weeks prior to Randomization
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Diagnostic and Medical Clinic - Mobile | Mobile | Alabama | United States | 36604 |
| 2 | The Research Center of Southern California | Carlsbad | California | United States | 92011 |
| 3 | UCLA Medical Center | Los Angeles | California | United States | 90095 |
| 4 | University of California Irvine Health ALS and Neuromuscular Center | Orange | California | United States | 92868 |
| 5 | Yale University | New Haven | Connecticut | United States | 06520 |
| 6 | George Washington University | Washington | District of Columbia | United States | 20052 |
| 7 | University of Florida | Jacksonville | Florida | United States | 32209 |
| 8 | University of South Florida | Tampa | Florida | United States | 33620 |
| 9 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
| 10 | University of Kansas Medical Center | Kansas City | Kansas | United States | 66160 |
| 11 | University of Maryland | Baltimore | Maryland | United States | 21201 |
| 12 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 13 | Lahey Hospital and Medical Center | Burlington | Massachusetts | United States | 01805 |
| 14 | Wayne State University | Detroit | Michigan | United States | 48202 |
| 15 | Michigan State University | East Lansing | Michigan | United States | 48864 |
| 16 | University of Buffalo | Buffalo | New York | United States | 14260 |
| 17 | Hospital for Special Surgery | New York | New York | United States | 10021 |
| 18 | Mount Sinai Hospital | New York | New York | United States | 10029 |
| 19 | University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | United States | 27599 |
| 20 | Ohio State University | Columbus | Ohio | United States | 43210 |
| 21 | Allegheny Neurological Associates | Pittsburgh | Pennsylvania | United States | 15212 |
| 22 | Wesley Neurology Clinic | Cordova | Tennessee | United States | 38018 |
| 23 | University of Texas Southwestern | Dallas | Texas | United States | 75390 |
| 24 | University of Utah | Salt Lake City | Utah | United States | 84132 |
| 25 | University of Vermont | Burlington | Vermont | United States | 05405 |
| 26 | Center for Neurological Disorders | Milwaukee | Wisconsin | United States | 53215 |
| 27 | University of Alberta Hospital | Edmonton | Alberta | Canada | T6G 2B7 |
| 28 | London Health Sciences Centre University Hospital | London | Ontario | Canada | N6A 5A5 |
| 29 | Toronto General Hospital | Toronto | Ontario | Canada | M5G 2C4 |
| 30 | Montreal Neurological Institute and Hospital | Montreal | Quebec | Canada | H3A 2B4 |
Sponsors and Collaborators
- Ra Pharmaceuticals
Investigators
- Study Director: UCB Cares, 001 844 599 2273 (UCB)
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Ra Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT03315130
Other Study ID Numbers:
- RA101495-02.201
First Posted:
Oct 19, 2017
Last Update Posted:
Jul 27, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study started to enroll participants in October 2017 and concluded in November 2020. |
|---|---|
| Pre-assignment Detail | The Participant flow refers to the Intent-to-treat Set for the main portion and Safety Set for the extension portion. |
| Arm/Group Title | RA101495 0.1 mg/kg | RA101495 0.3 mg/kg | Placebo | RA101495 0.1 mg/kg (Before Switch) to 0.3 mg/kg (After Switch) |
|---|---|---|---|---|
| Arm/Group Description | Participants received RA101495 0.1 milligram/kilogram (mg/kg) as a subcutaneous injection once daily for 12 weeks in the main portion. Participants who completed main portion and were eligible to enter in the extension portion, continued receiving RA101495 0.1 mg/kg up to 48 weeks (until protocol amendment v3.0) in the extension portion (EP). | Participants received RA101495 0.3 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. At the end of the treatment period in the main portion, participants received the same dose of study drug in the extension portion until RA101495 is approved and available in the territory, or the sponsor terminates development of RA101495 for generalized myasthenia gravis (gMG). In countries where RA101495 is not approved or marketed, but in which sponsored clinical studies had been conducted, participants received RA101495 through a compassionate use pathway in the extension portion (up to 122 weeks). | Participants received placebo matched to RA101495 as a subcutaneous injection once daily for 12 weeks in the main portion. At the end of the treatment period in the main portion, participants were randomized to receive either RA101495 0.1 mg/kg (up to 48 weeks) or RA101495 0.3 mg/kg (up to 122 weeks) in the extension portion, as a subcutaneous injection once daily. | Following implementation of protocol amendment v3.0, and upon appropriate reconsent, all study participants ongoing in the extension portion who had previously received the RA101495 0.1mg/kg/day dose switched to receive the RA101495 0.3mg/kg/day until RA101495 is approved and available in the territory, or the sponsor terminates development of RA101495 for gMG. In countries where RA101495 is not approved or marketed, but in which sponsored clinical studies had been conducted, participants received RA101495 through a compassionate use pathway in the extension portion (up to 122 weeks). |
| Period Title: Main Portion (12 Weeks) | ||||
| STARTED | 15 | 15 | 15 | 0 |
| COMPLETED | 15 | 13 | 15 | 0 |
| NOT COMPLETED | 0 | 2 | 0 | 0 |
| Period Title: Main Portion (12 Weeks) | ||||
| STARTED | 22 | 21 | 0 | 0 |
| COMPLETED | 21 | 21 | 0 | 0 |
| NOT COMPLETED | 1 | 0 | 0 | 0 |
| Period Title: Main Portion (12 Weeks) | ||||
| STARTED | 0 | 21 | 0 | 21 |
| COMPLETED | 0 | 17 | 0 | 20 |
| NOT COMPLETED | 0 | 4 | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | RA101495 0.1 mg/kg | RA101495 0.3 mg/kg | Placebo | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants received RA101495 0.1 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants who completed main portion and were eligible to enter in the extension period, continued receiving RA101495 0.1 mg/kg up to 48 weeks (until protocol amendment v3.0) in the extension portion. | Participants received RA101495 0.3 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. At the end of the treatment period in the main portion, participants received the same dose of study drug in the extension portion until RA101495 is approved and available in the territory, or the sponsor terminates development of RA101495 for generalized myasthenia gravis (gMG). In countries where RA101495 is not approved or marketed, but in which sponsored clinical studies had been conducted, participants received RA101495 through a compassionate use pathway in the extension portion (up to 122 weeks). | Participants received placebo matched to RA101495 as a subcutaneous injection once daily for 12 weeks in the main portion. At the end of the treatment period in the main portion, participants were randomized to receive either RA101495 0.1 mg/kg (up to 48 weeks) or RA101495 0.3 mg/kg (up to 122 weeks) in the extension portion, as a subcutaneous injection once daily. | Total of all reporting groups |
| Overall Participants | 15 | 15 | 15 | 45 |
| Age (Count of Participants) | ||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
14
93.3%
|
11
73.3%
|
13
86.7%
|
38
84.4%
|
| >=65 years |
1
6.7%
|
4
26.7%
|
2
13.3%
|
7
15.6%
|
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
45.5
(15.6)
|
54.5
(14.9)
|
48.4
(15.7)
|
49.5
(15.5)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
8
53.3%
|
5
33.3%
|
11
73.3%
|
24
53.3%
|
| Male |
7
46.7%
|
10
66.7%
|
4
26.7%
|
21
46.7%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Asian |
0
0%
|
1
6.7%
|
1
6.7%
|
2
4.4%
|
| Black or African American |
2
13.3%
|
3
20%
|
2
13.3%
|
7
15.6%
|
| White |
13
86.7%
|
11
73.3%
|
12
80%
|
36
80%
|
Outcome Measures
| Title | Main Portion: Change From Baseline to Week 12 in Quantitative Myasthenia Gravis (QMG) Score |
|---|---|
| Description | The QMG is a standardized and validated quantitative strength scoring system that was developed specifically for myasthenia gravis (MG). The scale consists of 13 individual assessments, each scored on a 0-3 point scale (i.e., 0=none, 1=mild, 2=moderate, and 3=severe). The total score is the sum of the individual scores with a range of 0-39. Higher scores are representative of more severe impairment. |
| Time Frame | From Baseline to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The modified ITT (mITT) population included all participants in the ITT population who had received at least 1 dose of study drug. |
| Arm/Group Title | RA101495 0.1 mg/kg (mITT) | RA101495 0.3 mg/kg (mITT) | Placebo (mITT) |
|---|---|---|---|
| Arm/Group Description | Participants received RA101495 0.1 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the mITT population which included all participants in the ITT population who had received at least 1 dose of study drug. | Participants received RA101495 0.3 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the mITT population which included all participants in the ITT population who had received at least 1 dose of study drug. | Participants received placebo matched to RA101495 as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the mITT population which included all participants in the ITT population who had received at least 1 dose of study drug. |
| Measure Participants | 15 | 14 | 15 |
| Least Squares Mean (Standard Error) [score on a scale] |
-5.5
(1.2)
|
-6.0
(1.2)
|
-3.2
(1.2)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | RA101495 0.1 mg/kg (mITT), Placebo (mITT) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.0941 |
| Comments | 1-sided p-value is presented for each active treatment arm compared to the Placebo treatment arm. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -2.3 | |
| Confidence Interval |
(2-Sided) 80% -4.5 to -0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.7 |
|
| Estimation Comments | LS mean difference and associated confidence interval are presented for each active treatment arm compared to the Placebo treatment arm. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | RA101495 0.3 mg/kg (mITT), Placebo (mITT) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.0538 |
| Comments | 1-sided p-value is presented for each active treatment arm compared to the Placebo treatment arm. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -2.8 | |
| Confidence Interval |
(2-Sided) 80% -5.1 to -0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.7 |
|
| Estimation Comments | LS mean difference and associated confidence interval are presented for each active treatment arm compared to the Placebo treatment arm. | |
| Title | Main Portion: Change From Baseline to Week 12 in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) Scale |
|---|---|
| Description | The MG-ADL is a brief 8-item survey designed to evaluate MG symptom severity. The scale consists of 8 items each scored on a 0-3 point scale (i.e., 0=none, 1=mild, 2=moderate, and 3=severe). The total score is the sum of the 8 individual scores with range of 0-24. Higher scores are associated with more severe symptoms of MG. |
| Time Frame | From Baseline to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The mITT population included all participants in the ITT population who had received at least 1 dose of study drug. |
| Arm/Group Title | RA101495 0.1 mg/kg (mITT) | RA101495 0.3 mg/kg (mITT) | Placebo (mITT) |
|---|---|---|---|
| Arm/Group Description | Participants received RA101495 0.1 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the mITT population which included all participants in the ITT population who had received at least 1 dose of study drug. | Participants received RA101495 0.3 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the mITT population which included all participants in the ITT population who had received at least 1 dose of study drug. | Participants received placebo matched to RA101495 as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the mITT population which included all participants in the ITT population who had received at least 1 dose of study drug. |
| Measure Participants | 15 | 14 | 15 |
| Least Squares Mean (Standard Error) [score on a scale] |
-3.3
(0.9)
|
-3.4
(0.9)
|
-1.1
(0.9)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | RA101495 0.1 mg/kg (mITT), Placebo (mITT) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.0470 |
| Comments | 1-sided p-value is presented for each active treatment arm compared to the Placebo treatment arm. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -2.2 | |
| Confidence Interval |
(2-Sided) 80% -3.9 to -0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.3 |
|
| Estimation Comments | LS mean difference and associated confidence interval are presented for each active treatment arm compared to the Placebo treatment arm. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | RA101495 0.3 mg/kg (mITT), Placebo (mITT) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.0392 |
| Comments | 1-sided p-value is presented for each active treatment arm compared to the Placebo treatment arm. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -2.3 | |
| Confidence Interval |
(2-Sided) 80% -4.0 to -0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.3 |
|
| Estimation Comments | LS mean difference and associated confidence interval are presented for each active treatment arm compared to the Placebo treatment arm. | |
| Title | Main Portion: Change From Baseline to Week 12 in the Myasthenia Gravis - Quality of Life 15r (MG-QOL15r) Survey |
|---|---|
| Description | The MG-QOL15r is a 15-item survey that was designed to assess quality of life in participants with MG. The survey consisted of 15 questions and the corresponding responses were each scored on a 0-2 point scale (0=Not much at all, 1=Somewhat, 2=Very Much). The total score is the sum of the 15 individual item scores with a range of 0-30. Higher scores indicate more severe impact of the disease on aspects of the participant's life. |
| Time Frame | From Baseline to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The mITT population included all participants in the ITT population who had received at least 1 dose of study drug. |
| Arm/Group Title | RA101495 0.1 mg/kg (mITT) | RA101495 0.3 mg/kg (mITT) | Placebo (mITT) |
|---|---|---|---|
| Arm/Group Description | Participants received RA101495 0.1 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the mITT population which included all participants in the ITT population who had received at least 1 dose of study drug. | Participants received RA101495 0.3 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the mITT population which included all participants in the ITT population who had received at least 1 dose of study drug. | Participants received placebo matched to RA101495 as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the mITT population which included all participants in the ITT population who had received at least 1 dose of study drug. |
| Measure Participants | 15 | 14 | 15 |
| Least Squares Mean (Standard Error) [score on a scale] |
-7.4
(1.7)
|
-5.9
(1.7)
|
-2.1
(1.7)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | RA101495 0.1 mg/kg (mITT), Placebo (mITT) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.0170 |
| Comments | 1-sided p-value is presented for each active treatment arm compared to the Placebo treatment arm. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -5.3 | |
| Confidence Interval |
(2-Sided) 80% -8.4 to -2.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.4 |
|
| Estimation Comments | LS mean difference and associated confidence interval are presented for each active treatment arm compared to the Placebo treatment arm. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | RA101495 0.3 mg/kg (mITT), Placebo (mITT) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.0624 |
| Comments | 1-sided p-value is presented for each active treatment arm compared to the Placebo treatment arm. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -3.7 | |
| Confidence Interval |
(2-Sided) 80% -6.9 to -0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.4 |
|
| Estimation Comments | LS mean difference and associated confidence interval are presented for each active treatment arm compared to the Placebo treatment arm. | |
| Title | Main Portion: Change From Baseline to Week 12 in the MG Composite Scale Total Score |
|---|---|
| Description | The MG Composite is a 10-item scale that has been used to measure the clinical status of participants with MG, in order to evaluate treatment response. It consists of 10 items which included ptosis (score range=0 to 3), double vision on lateral gaze left/right/both (score range=0 to 4), eye closure (score range=0 to 2), talking (score range=0 to 6), chewing (score range=0 to 6), swallowing (score range=0 to 6), breathing (score range=0 to 9), neck flexion or extension (score range=0 to 4), shoulder abduction (score range=0 to 5) and hip flexion (score range= 0 to 5). The total score is the sum of the 10 individual scores with a range of 0-50. Higher scores in the MG Composite indicate more severe impairment due to the disease. |
| Time Frame | From Baseline to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The mITT population included all participants in the ITT population who had received at least 1 dose of study drug. |
| Arm/Group Title | RA101495 0.1 mg/kg (mITT) | RA101495 0.3 mg/kg (mITT) | Placebo (mITT) |
|---|---|---|---|
| Arm/Group Description | Participants received RA101495 0.1 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the mITT population which included all participants in the ITT population who had received at least 1 dose of study drug. | Participants received RA101495 0.3 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the mITT population which included all participants in the ITT population who had received at least 1 dose of study drug. | Participants received placebo matched to RA101495 as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the mITT population which included all participants in the ITT population who had received at least 1 dose of study drug. |
| Measure Participants | 15 | 14 | 15 |
| Least Squares Mean (Standard Error) [score on a scale] |
-5.3
(1.5)
|
-7.4
(1.6)
|
-3.3
(1.6)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | RA101495 0.1 mg/kg (mITT), Placebo (mITT) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.1866 |
| Comments | 1-sided p-value is presented for each active treatment arm compared to the Placebo treatment arm. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -2.0 | |
| Confidence Interval |
(2-Sided) 80% -4.9 to 0.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.2 |
|
| Estimation Comments | LS mean difference and associated confidence interval are presented for each active treatment arm compared to the Placebo treatment arm. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | RA101495 0.3 mg/kg (mITT), Placebo (mITT) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.0391 |
| Comments | 1-sided p-value is presented for each active treatment arm compared to the Placebo treatment arm. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -4.1 | |
| Confidence Interval |
(2-Sided) 80% -7.0 to -1.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.2 |
|
| Estimation Comments | LS mean difference and associated confidence interval are presented for each active treatment arm compared to the Placebo treatment arm. | |
| Title | Main Portion: Percentage of Participants With >= 3-point Reduction in QMG Total Score at Week 12 |
|---|---|
| Description | The QMG is a standardized and validated quantitative strength scoring system that was developed specifically for MG. The scale consists of 13 individual assessments, each scored on a 0-3 point scale (i.e., 0=none, 1=mild, 2=moderate, and 3=severe). The total score is the sum of the individual scores with a range of 0-39. Higher scores are representative of more severe impairment. |
| Time Frame | Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The mITT population included all participants in the ITT population who had received at least 1 dose of study drug. |
| Arm/Group Title | RA101495 0.1 mg/kg (mITT) | RA101495 0.3 mg/kg (mITT) | Placebo (mITT) |
|---|---|---|---|
| Arm/Group Description | Participants received RA101495 0.1 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the mITT population which included all participants in the ITT population who had received at least 1 dose of study drug. | Participants received RA101495 0.3 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the mITT population which included all participants in the ITT population who had received at least 1 dose of study drug. | Participants received placebo matched to RA101495 as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the mITT population which included all participants in the ITT population who had received at least 1 dose of study drug. |
| Measure Participants | 15 | 14 | 15 |
| Number [percentage of participants] |
66.7
444.7%
|
71.4
476%
|
53.3
355.3%
|
| Title | Main Portion: Percentage of Participants Who Required Rescue Therapy Over the 12-week Treatment Period |
|---|---|
| Description | Percentage of participants who used at least 1 dose of rescue medication were reported. |
| Time Frame | Up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The mITT population included all participants in the ITT population who had received at least 1 dose of study drug. |
| Arm/Group Title | RA101495 0.1 mg/kg (mITT) | RA101495 0.3 mg/kg (mITT) | Placebo (mITT) |
|---|---|---|---|
| Arm/Group Description | Participants received RA101495 0.1 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the mITT population which included all participants in the ITT population who had received at least 1 dose of study drug. | Participants received RA101495 0.3 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the mITT population which included all participants in the ITT population who had received at least 1 dose of study drug. | Participants received placebo matched to RA101495 as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the mITT population which included all participants in the ITT population who had received at least 1 dose of study drug. |
| Measure Participants | 15 | 14 | 15 |
| Number [percentage of participants] |
6.7
44.7%
|
0
0%
|
20.0
133.3%
|
| Title | Main Portion: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
|---|---|
| Description | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A serious adverse event (SAE) is any untoward medical occurrence that at any dose resulted in death, life-threatening, significant or persistent disability/incapacity, congenital anomaly/birth defect, important medical event, initial inpatient hospitalization or prolongation of hospitalization. |
| Time Frame | From Baseline to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population included all participants who had received at least 1 dose of study drug (i.e., mITT Population), with participants to be analyzed based on the actual treatment received. |
| Arm/Group Title | RA101495 0.1 mg/kg (SS) | RA101495 0.3 mg/kg (SS) | Placebo (SS) |
|---|---|---|---|
| Arm/Group Description | Participants received RA101495 0.1 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the safety set (SS) population which included all participants who had received at least 1 dose of study drug (i.e., mITT Population), with participants to be analyzed based on the actual treatment received. | Participants received RA101495 0.3 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the SS population which included all participants who had received at least 1 dose of study drug (i.e., mITT Population), with participants to be analyzed based on the actual treatment received. | Participants received placebo matched to RA101495 as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the SS population which included all participants who had received at least 1 dose of study drug (i.e., mITT Population), with participants to be analyzed based on the actual treatment received. |
| Measure Participants | 15 | 14 | 15 |
| AEs |
15
100%
|
12
80%
|
14
93.3%
|
| SAEs |
0
0%
|
5
33.3%
|
3
20%
|
| Title | Main Portion: Change From Baseline in Sheep Red Blood Cell (sRBC) Lysis Assay at Week 12 (Pre-dose) |
|---|---|
| Description | A BioTek ELx800 automated microplate reader is used to measure the optical density at 415 nanometer (nm) of human plasma samples to calculate the percent lysis of sheep erythrocytes that has occurred as a result of total complement activity. The measure of complement activity is determined by the degree of hemolysis of the erythrocytes. |
| Time Frame | Baseline and Week 12 (Pre-dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacodynamic (PD) population included all participants in mITT Population who had at least 1 evaluable PD assessment. |
| Arm/Group Title | RA101495 0.1 mg/kg (PD) | RA101495 0.3 mg/kg (PD) | Placebo (PD) |
|---|---|---|---|
| Arm/Group Description | Participants received RA101495 0.1 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed PD population which included all participants in mITT population who had at least 1 evaluable PD assessment. | Participants received RA101495 0.3 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed PD population which included all participants in mITT population who had at least 1 evaluable PD assessment. | Participants received placebo matched to RA101495 as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed PD population which included all participants in mITT population who had at least 1 evaluable PD assessment. |
| Measure Participants | 15 | 14 | 15 |
| Least Squares Mean (Standard Error) [percent lysis of sheep erythrocytes] |
-81.822
(2.469)
|
-94.914
(2.908)
|
0.775
(2.571)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | RA101495 0.1 mg/kg (mITT), Placebo (mITT) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 1-sided p-value is presented for each active treatment arm compared to the Placebo treatment arm. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -82.597 | |
| Confidence Interval |
(2-Sided) 80% -87.249 to -77.946 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.563 |
|
| Estimation Comments | LS mean difference and associated confidence interval are presented for each active treatment arm compared to the Placebo treatment arm. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | RA101495 0.3 mg/kg (mITT), Placebo (mITT) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 1-sided p-value is presented for each active treatment arm compared to the Placebo treatment arm. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -95.689 | |
| Confidence Interval |
(2-Sided) 80% -100.794 to -90.585 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.910 |
|
| Estimation Comments | LS mean difference and associated confidence interval are presented for each active treatment arm compared to the Placebo treatment arm. | |
| Title | Main Portion: Change From Baseline in C5 Levels at Week 12 (Pre-dose) |
|---|---|
| Description | Blood samples were collected from participants to assess Complement Component 5C levels. |
| Time Frame | Baseline and Week 12 (Pre-dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD population included all participants in mITT Population who had at least 1 evaluable PD assessment. |
| Arm/Group Title | RA101495 0.1 mg/kg (PD) | RA101495 0.3 mg/kg (PD) | Placebo (PD) |
|---|---|---|---|
| Arm/Group Description | Participants received RA101495 0.1 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed PD population which included all participants in mITT population who had at least 1 evaluable PD assessment. | Participants received RA101495 0.3 mg/kg as a subcutaneous injection once daily for 12 weeks in main portion. Participants formed PD population which included all participants in mITT population who had at least 1 evaluable PD assessment. | Participants received placebo matched to RA101495 as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed PD population which included all participants in mITT population who had at least 1 evaluable PD assessment. |
| Measure Participants | 15 | 14 | 15 |
| Least Squares Mean (Standard Error) [micrograms/milliliter (ug/mL)] |
57.349
(7.057)
|
54.302
(6.804)
|
-2.774
(6.237)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | RA101495 0.1 mg/kg (mITT), Placebo (mITT) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 1-sided p-value is presented for each active treatment arm compared to the Placebo treatment arm. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 60.123 | |
| Confidence Interval |
(2-Sided) 80% 47.839 to 72.408 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 9.394 |
|
| Estimation Comments | LS mean difference and associated confidence interval are presented for each active treatment arm compared to the Placebo treatment arm. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | RA101495 0.3 mg/kg (mITT), Placebo (mITT) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 1-sided p-value is presented for each active treatment arm compared to the Placebo treatment arm. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 57.076 | |
| Confidence Interval |
(2-Sided) 80% 44.955 to 69.197 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 9.269 |
|
| Estimation Comments | LS mean difference and associated confidence interval are presented for each active treatment arm compared to the Placebo treatment arm. | |
| Title | Main Portion: Plasma Concentration of RA101495 and Its Major Metabolites |
|---|---|
| Description | RA102758 and RA103488 are the metabolites of RA101495. |
| Time Frame | 1, 3 and 6 hours postdose on Day 1; Pre-dose on Week 1, 2, 4, 8 and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacokinetic (PK) population included all participants in mITT population who had at least 1 evaluable PK assessment. Here "Number Analyzed" signifies number of participants who were evaluable at specified time points. 1 Participant (who was randomized to Placebo) mistakenly received Zilucoplan on Day 1 following a dispensing error (which was documented as a minor PD). Due to data confidentiality reasons, the results have not been reported for the placebo arm. |
| Arm/Group Title | RA101495 0.1 mg/kg (PK) | RA101495 0.3 mg/kg (PK) |
|---|---|---|
| Arm/Group Description | Participants received RA101495 0.1 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the PK population which included all participants in mITT population who had at least 1 evaluable PK assessment. | Participants received RA101495 0.3 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the PK population which included all participants in mITT population who had at least 1 evaluable PK assessment. |
| Measure Participants | 15 | 14 |
| RA101495- Day 1: 1 hour postdose |
652.136
(354.652)
|
2272.257
(1246.128)
|
| RA101495- Day 1: 3 hours postdose |
1691.267
(469.766)
|
4176.000
(1211.166)
|
| RA101495- Day 1: 6 hours postdose |
1925.357
(330.335)
|
4636.000
(809.804)
|
| RA101495- Week 1: Pre-dose |
4571.214
(719.566)
|
9223.786
(2365.168)
|
| RA101495- Week 2: Pre-dose |
4914.200
(743.215)
|
10222.846
(1662.869)
|
| RA101495- Week 4: Pre-dose |
5100.286
(859.767)
|
10265.917
(1604.004)
|
| RA101495- Week 8: Pre-dose |
5222.067
(688.427)
|
10075.000
(1872.400)
|
| RA101495- Week 12: Pre-dose |
5281.333
(1122.372)
|
10284.846
(1771.586)
|
| RA102758- Day 1: 1 hour postdose |
NA
(NA)
|
NA
(NA)
|
| RA102758- Day 1: 3 hours postdose |
NA
(NA)
|
NA
(NA)
|
| RA102758- Day 1: 6 hours postdose |
NA
(NA)
|
NA
(NA)
|
| RA102758- Week 1: Pre-dose |
252.693
(78.909)
|
849.743
(273.388)
|
| RA102758- Week 2: Pre-dose |
408.847
(94.773)
|
1473.431
(440.496)
|
| RA102758- Week 4: Pre-dose |
462.486
(180.098)
|
1567.692
(557.745)
|
| RA102758- Week 8: Pre-dose |
474.073
(157.549)
|
1432.808
(530.377)
|
| RA102758- Week 12: Pre-dose |
465.665
(195.227)
|
1459.062
(451.013)
|
| RA103488- Day 1: 1 hour postdose |
NA
(NA)
|
NA
(NA)
|
| RA103488- Day 1: 3 hours postdose |
NA
(NA)
|
NA
(NA)
|
| RA103488- Day 1: 6 hours postdose |
NA
(NA)
|
85.832
(257.664)
|
| RA103488- Week 1: Pre-dose |
356.186
(162.209)
|
838.907
(255.419)
|
| RA103488- Week 2: Pre-dose |
501.847
(218.467)
|
1135.731
(270.004)
|
| RA103488- Week 4: Pre-dose |
536.266
(275.013)
|
1191.783
(251.853)
|
| RA103488- Week 8: Pre-dose |
615.740
(229.359)
|
1234.708
(201.055)
|
| RA103488- Week 12: Pre-dose |
621.813
(241.354)
|
1307.492
(331.553)
|
| Title | Main Portion: Maximum Plasma Concentration (Cmax) on Day 1 |
|---|---|
| Description | Cmax is defined as the maximum observed plasma concentration. |
| Time Frame | Pre-dose, 1, 3 and 6 hours postdose on Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK Population included all participants in mITT population who had at least 1 evaluable PK assessment. 1 Participant (who was randomized to Placebo) mistakenly received Zilucoplan on Day 1 following a dispensing error (which was documented as a minor PD). Due to data confidentiality reasons, the results have not been reported for the placebo arm. |
| Arm/Group Title | RA101495 0.1 mg/kg (PK) | RA101495 0.3 mg/kg (PK) |
|---|---|---|
| Arm/Group Description | Participants received RA101495 0.1 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the PK population which included all participants in mITT population who had at least 1 evaluable PK assessment. | Participants received RA101495 0.3 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the PK population which included all participants in mITT population who had at least 1 evaluable PK assessment. |
| Measure Participants | 15 | 14 |
| Mean (Standard Deviation) [ng/mL] |
1945.467
(407.273)
|
4858.643
(1004.457)
|
| Title | Main Portion: Time Corresponding to Cmax (Tmax) on Day 1 |
|---|---|
| Description | Tmax is defined as the time to observe maximum plasma concentration. |
| Time Frame | Pre-dose, 1, 3 and 6 hours postdose on Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK Population included all participants in mITT population who had at least 1 evaluable PK assessment. 1 Participant (who was randomized to Placebo) mistakenly received Zilucoplan on Day 1 following a dispensing error (which was documented as a minor PD). Due to data confidentiality reasons, the results have not been reported for the placebo arm. |
| Arm/Group Title | RA101495 0.1 mg/kg (PK) | RA101495 0.3 mg/kg (PK) |
|---|---|---|
| Arm/Group Description | Participants received RA101495 0.1 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the PK population which included all participants in mITT population who had at least 1 evaluable PK assessment. | Participants received RA101495 0.3 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the PK population which included all participants in mITT population who had at least 1 evaluable PK assessment. |
| Measure Participants | 15 | 14 |
| Median (Full Range) [hours] |
4.550
|
4.700
|
| Title | Main Portion: Metabolites (RA102758 and RA103488) to Parent Ratio |
|---|---|
| Description | RA102758 and RA103488 are the metabolites of RA101495. |
| Time Frame | Pre-dose, 1, 3 and 6 hours postdose on Day 1; Pre-dose on Week 1, 2, 4, 8 and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK Population included all participants in mITT population who had at least 1 evaluable PK assessment. Here "Number Analyzed" signifies number of participants who were evaluable at specified time points. 1 Participant (who was randomized to Placebo) mistakenly received Zilucoplan on Day 1 following a dispensing error (which was documented as a minor PD). Due to data confidentiality reasons, the results have not been reported for the placebo arm. |
| Arm/Group Title | RA101495 0.1 mg/kg (PK) | RA101495 0.3 mg/kg (PK) |
|---|---|---|
| Arm/Group Description | Participants received RA101495 0.1 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the PK population which included all participants in mITT population who had at least 1 evaluable PK assessment. | Participants received RA101495 0.3 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants formed the PK population which included all participants in mITT population who had at least 1 evaluable PK assessment. |
| Measure Participants | 15 | 14 |
| RA102758/RA101495- Day 1: Pre-dose |
NA
(NA)
|
NA
(NA)
|
| RA102758/RA101495- Day 1: 1 hour postdose |
0.000
(0.000)
|
0.000
(0.000)
|
| RA102758/RA101495- Day 1: 3 hours postdose |
0.000
(0.000)
|
0.000
(0.000)
|
| RA102758/RA101495- Day 1: 6 hours postdose |
0.000
(0.000)
|
0.013
(0.044)
|
| RA102758/RA101495- Week 1: Pre-dose |
0.121
(0.033)
|
0.202
(0.038)
|
| RA102758/RA101495- Week 2: Pre-dose |
0.182
(0.038)
|
0.307
(0.057)
|
| RA102758/RA101495- Week 4: Pre-dose |
0.197
(0.072)
|
0.323
(0.072)
|
| RA102758/RA101495- Week 8: Pre-dose |
0.195
(0.057)
|
0.301
(0.070)
|
| RA102758/RA101495- Week 12: Pre-dose |
0.184
(0.065)
|
0.303
(0.061)
|
| RA103488/RA101495- Day 1: Pre-dose |
NA
(NA)
|
NA
(NA)
|
| RA103488/RA101495- Day 1: 1 hour postdose |
0.000
(0.000)
|
0.000
(0.000)
|
| RA103488/RA101495- Day 1: 3 hours postdose |
0.000
(0.000)
|
0.001
(0.001)
|
| RA103488/RA101495- Day 1: 6 hours postdose |
0.000
(0.000)
|
0.015
(0.045)
|
| RA103488/RA101495- Week 1: Pre-dose |
0.079
(0.037)
|
0.099
(0.044)
|
| RA103488/RA101495- Week 2: Pre-dose |
0.104
(0.044)
|
0.114
(0.037)
|
| RA103488/RA101495- Week 4: Pre-dose |
0.106
(0.046)
|
0.119
(0.038)
|
| RA103488/RA101495- Week 8: Pre-dose |
0.118
(0.044)
|
0.127
(0.040)
|
| RA103488/RA101495- Week 12: Pre-dose |
0.116
(0.035)
|
0.131
(0.041)
|
Adverse Events
| Time Frame | From Baseline up to Week 122 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Treatment emergent adverse events (TEAEs) are defined as an AE that occurs after a treatment start date or an AE that increases in severity after treatment start date. In this study, AEs were planned to be reported for Main portion and Main + Extension portion only. | |||||||||||
| Arm/Group Title | Main Portion: RA101495 0.1 mg/kg | Main Portion: RA101495 0.3 mg/kg | Main Portion: Placebo | Main and Extension Portion: RA101495 0.1 mg/kg Before Switch to 0.3 mg/kg | Main and Extension Portion: RA101495 0.1 mg/kg After Switch to 0.3 mg/kg | Main and Extension Portion: RA101495 0.3 mg/kg | ||||||
| Arm/Group Description | Participants received RA101495 0.1 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. | Participants received RA101495 0.3 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion | Participants received placebo matched to RA101495 as a subcutaneous injection once daily for 12 weeks in the main portion. | Participants received RA101495 0.1 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants who completed main portion and were eligible to enter in the extension period, continued receiving RA101495 0.1 mg/kg up to 48 weeks (until protocol amendment v3.0) in the extension portion. | Participants received RA101495 0.1 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. Participants who completed main portion and were eligible to enter in the extension period, continued receiving RA101495 0.1 mg/kg up to Week 48 (until protocol amendment v3.0). Following implementation of protocol amendment v3.0, and upon appropriate reconsent, all study participants ongoing in the extension portion who had previously received the RA101495 0.1mg/kg/day dose switched to receive the RA101495 0.3mg/kg/day until RA101495 is approved and available in the territory, or the sponsor terminates development of RA101495 for gMG. In countries where RA101495 is not approved or marketed, but in which sponsored clinical studies had been conducted, participants received RA101495 through a compassionate use pathway in the extension portion (up to 122 weeks). | Participants received RA101495 0.3 mg/kg as a subcutaneous injection once daily for 12 weeks in the main portion. At the end of the treatment period in the main portion, participants received the same dose of study drug in the extension portion until RA101495 is approved and available in the territory, or the sponsor terminates development of RA101495 for gMG. In countries where RA101495 is not approved or marketed, but in which sponsored clinical studies had been conducted, participants received RA101495 through a compassionate use pathway in the extension portion (up to 122 weeks). | ||||||
All Cause Mortality |
||||||||||||
| Main Portion: RA101495 0.1 mg/kg | Main Portion: RA101495 0.3 mg/kg | Main Portion: Placebo | Main and Extension Portion: RA101495 0.1 mg/kg Before Switch to 0.3 mg/kg | Main and Extension Portion: RA101495 0.1 mg/kg After Switch to 0.3 mg/kg | Main and Extension Portion: RA101495 0.3 mg/kg | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/15 (0%) | 0/14 (0%) | 0/15 (0%) | 1/22 (4.5%) | 0/21 (0%) | 2/21 (9.5%) | ||||||
Serious Adverse Events |
||||||||||||
| Main Portion: RA101495 0.1 mg/kg | Main Portion: RA101495 0.3 mg/kg | Main Portion: Placebo | Main and Extension Portion: RA101495 0.1 mg/kg Before Switch to 0.3 mg/kg | Main and Extension Portion: RA101495 0.1 mg/kg After Switch to 0.3 mg/kg | Main and Extension Portion: RA101495 0.3 mg/kg | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/15 (0%) | 5/14 (35.7%) | 3/15 (20%) | 5/22 (22.7%) | 4/21 (19%) | 11/21 (52.4%) | ||||||
| Cardiac disorders | ||||||||||||
| Atrial fibrillation | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 2 |
| Atrial flutter | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Bradycardia | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 |
| Cardiac arrest | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Myocardial infarction | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Gastrointestinal disorders | ||||||||||||
| Pancreatic cyst | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Pancreatitis acute | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Abdominal pain | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 |
| Gastric ulcer | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 |
| Intra-abdominal fluid collection | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| General disorders | ||||||||||||
| Systemic inflammatory response syndrome | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Non-cardiac chest pain | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Hepatobiliary disorders | ||||||||||||
| Cholecystitis | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
| Infections and infestations | ||||||||||||
| Cellulitis | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Abdominal abscess | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Diverticulitis | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Pneumonia | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 2/22 (9.1%) | 2 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 |
| Pancreas infection | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
| Gastrointestinal infection | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Liver abscess | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Sepsis | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 |
| Staphylococcal bacteraemia | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| COVID-19 | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||
| Post procedural complication | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
| Postoperative hypertension | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Spinal fracture | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Investigations | ||||||||||||
| Blood culture positive | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Fibrin D dimer increased | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Back pain | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Rapidly progressive osteoarthritis | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Musculoskeletal chest pain | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
| Pancreatic carcinoma | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Nervous system disorders | ||||||||||||
| Worsening of Myasthenia Gravis | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 3/15 (20%) | 3 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Syncope | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Renal and urinary disorders | ||||||||||||
| Nephrolithiasis | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 1/21 (4.8%) | 2 | 0/21 (0%) | 0 |
| Ureterolithiasis | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Respiratory failure | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||||
| Main Portion: RA101495 0.1 mg/kg | Main Portion: RA101495 0.3 mg/kg | Main Portion: Placebo | Main and Extension Portion: RA101495 0.1 mg/kg Before Switch to 0.3 mg/kg | Main and Extension Portion: RA101495 0.1 mg/kg After Switch to 0.3 mg/kg | Main and Extension Portion: RA101495 0.3 mg/kg | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 15/15 (100%) | 12/14 (85.7%) | 14/15 (93.3%) | 22/22 (100%) | 17/21 (81%) | 21/21 (100%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Iron deficiency anaemia | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 | 1/22 (4.5%) | 2 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 |
| Anaemia | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
| Increased tendency to bruise | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Lymphadenopathy | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 2 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Cardiac disorders | ||||||||||||
| Palpitations | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Ear and labyrinth disorders | ||||||||||||
| Vertigo | 0/15 (0%) | 0 | 1/14 (7.1%) | 2 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 2/21 (9.5%) | 3 |
| Eye disorders | ||||||||||||
| Cataract | 1/15 (6.7%) | 2 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 2 | 1/21 (4.8%) | 2 | 2/21 (9.5%) | 2 |
| Eyelid ptosis | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 2 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||
| Nausea | 2/15 (13.3%) | 3 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 4/22 (18.2%) | 7 | 1/21 (4.8%) | 1 | 5/21 (23.8%) | 8 |
| Vomiting | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 2/22 (9.1%) | 3 | 2/21 (9.5%) | 2 | 3/21 (14.3%) | 4 |
| Abdominal discomfort | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 |
| Abdominal pain upper | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
| Diarrhoea | 1/15 (6.7%) | 1 | 1/14 (7.1%) | 1 | 1/15 (6.7%) | 1 | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 5/21 (23.8%) | 6 |
| Constipation | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Dysphagia | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
| Dry mouth | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Lip dry | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Abdominal distension | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
| Mouth ulceration | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| General disorders | ||||||||||||
| Injection site bruising | 2/15 (13.3%) | 2 | 0/14 (0%) | 0 | 2/15 (13.3%) | 2 | 6/22 (27.3%) | 13 | 0/21 (0%) | 0 | 3/21 (14.3%) | 3 |
| Injection site scab | 3/15 (20%) | 4 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 3/22 (13.6%) | 4 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Injection site nodule | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 2/21 (9.5%) | 2 | 1/21 (4.8%) | 1 |
| Oedema peripheral | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 1/21 (4.8%) | 1 | 3/21 (14.3%) | 3 |
| Fatigue | 2/15 (13.3%) | 2 | 1/14 (7.1%) | 1 | 1/15 (6.7%) | 1 | 2/22 (9.1%) | 2 | 1/21 (4.8%) | 1 | 2/21 (9.5%) | 3 |
| Influenza like illness | 1/15 (6.7%) | 2 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 2/22 (9.1%) | 3 | 0/21 (0%) | 0 | 1/21 (4.8%) | 2 |
| Chills | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 |
| Pyrexia | 1/15 (6.7%) | 2 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 3 | 1/21 (4.8%) | 1 | 2/21 (9.5%) | 2 |
| Injection site pain | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 2 |
| Injection site discomfort | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 3 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Injection site haemorrhage | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Peripheral swelling | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 2 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Swelling face | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Pain | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Hepatobiliary disorders | ||||||||||||
| Biliary colic | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Infections and infestations | ||||||||||||
| Nasopharyngitis | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 6/22 (27.3%) | 9 | 5/21 (23.8%) | 6 | 8/21 (38.1%) | 8 |
| Upper respiratory tract infection | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 3/22 (13.6%) | 3 | 2/21 (9.5%) | 3 | 4/21 (19%) | 5 |
| Urinary tract infection | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 3/22 (13.6%) | 3 | 2/21 (9.5%) | 2 | 1/21 (4.8%) | 2 |
| Sinusitis | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 3/21 (14.3%) | 3 |
| Pharyngitis | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Viral upper respiratory tract infection | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 1/15 (6.7%) | 1 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
| Viral infection | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Bronchitis | 1/15 (6.7%) | 1 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 3/22 (13.6%) | 3 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
| Pneumonia | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Herpes zoster | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Localised infection | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Escherichia urinary tract infection | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Vaginal infection | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 2 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 3 |
| Injury, poisoning and procedural complications | ||||||||||||
| Contusion | 1/15 (6.7%) | 1 | 1/14 (7.1%) | 1 | 1/15 (6.7%) | 1 | 2/22 (9.1%) | 3 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Animal bite | 1/15 (6.7%) | 1 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Fall | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 2/21 (9.5%) | 2 | 0/21 (0%) | 0 |
| Foot fracture | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 2 |
| Limb injury | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Burns second degree | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Investigations | ||||||||||||
| Amylase increased | 0/15 (0%) | 0 | 2/14 (14.3%) | 2 | 1/15 (6.7%) | 1 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
| Lipase increased | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 2/15 (13.3%) | 3 | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Weight decreased | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Urine analysis abnormal | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Metabolism and nutrition disorders | ||||||||||||
| Dehydration | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 1/15 (6.7%) | 1 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
| Hyperglycaemia | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Glucose tolerance impaired | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Hypokalaemia | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Weight fluctuation | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Hypoglycaemia | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Muscle spasms | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 4/21 (19%) | 4 |
| Myalgia | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 4/21 (19%) | 4 |
| Muscular weakness | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 | 1/22 (4.5%) | 2 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 |
| Muscle twitching | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
| Back pain | 1/15 (6.7%) | 1 | 1/14 (7.1%) | 1 | 1/15 (6.7%) | 1 | 2/22 (9.1%) | 4 | 0/21 (0%) | 0 | 5/21 (23.8%) | 6 |
| Pain in extremity | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 2/21 (9.5%) | 2 | 1/21 (4.8%) | 3 |
| Arthralgia | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 | 2/22 (9.1%) | 2 | 1/21 (4.8%) | 1 | 3/21 (14.3%) | 5 |
| Tendonitis | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 |
| Musculoskeletal chest pain | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Neck pain | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Joint swelling | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 2/15 (13.3%) | 2 | 1/22 (4.5%) | 1 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 |
| Bursitis | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
| Squamous cell carcinoma | 0/15 (0%) | 0 | 2/14 (14.3%) | 2 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
| Basal cell carcinoma | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
| Nervous system disorders | ||||||||||||
| Headache | 6/15 (40%) | 6 | 3/14 (21.4%) | 3 | 4/15 (26.7%) | 5 | 10/22 (45.5%) | 13 | 3/21 (14.3%) | 4 | 4/21 (19%) | 10 |
| Dizziness | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 4/15 (26.7%) | 4 | 4/22 (18.2%) | 4 | 3/21 (14.3%) | 3 | 3/21 (14.3%) | 3 |
| Paraesthesia | 1/15 (6.7%) | 1 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 1/22 (4.5%) | 3 | 0/21 (0%) | 0 | 3/21 (14.3%) | 3 |
| Hypoaesthesia | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 2/22 (9.1%) | 3 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
| Worsening of Myasthenia Gravis | 2/15 (13.3%) | 2 | 1/14 (7.1%) | 1 | 2/15 (13.3%) | 2 | 4/22 (18.2%) | 6 | 0/21 (0%) | 0 | 3/21 (14.3%) | 3 |
| Migraine with aura | 0/15 (0%) | 0 | 1/14 (7.1%) | 4 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 4 |
| Somnolence | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Tremor | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Migraine | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
| Psychiatric disorders | ||||||||||||
| Insomnia | 1/15 (6.7%) | 1 | 1/14 (7.1%) | 1 | 1/15 (6.7%) | 1 | 2/22 (9.1%) | 2 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 |
| Depression | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 3/21 (14.3%) | 3 |
| Initial insomnia | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Sleep disorder | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 1/15 (6.7%) | 1 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Renal and urinary disorders | ||||||||||||
| Nephrolithiasis | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 3/21 (14.3%) | 3 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Cough | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 3/22 (13.6%) | 3 | 1/21 (4.8%) | 1 | 5/21 (23.8%) | 7 |
| Dyspnoea | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 2/15 (13.3%) | 2 | 1/22 (4.5%) | 2 | 2/21 (9.5%) | 2 | 1/21 (4.8%) | 2 |
| Nasal congestion | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 1/22 (4.5%) | 2 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
| Sleep apnoea syndrome | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Sinus congestion | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Pleurisy | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||
| Dermatitis contact | 1/15 (6.7%) | 1 | 2/14 (14.3%) | 2 | 1/15 (6.7%) | 1 | 2/22 (9.1%) | 4 | 0/21 (0%) | 0 | 3/21 (14.3%) | 3 |
| Rash | 1/15 (6.7%) | 1 | 1/14 (7.1%) | 2 | 0/15 (0%) | 0 | 1/22 (4.5%) | 2 | 0/21 (0%) | 0 | 2/21 (9.5%) | 8 |
| Miliaria | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 3/21 (14.3%) | 3 |
| Pruritus | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 2/15 (13.3%) | 2 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Cold sweat | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Nail discolouration | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Nail disorder | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Onychoclasis | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Actinic keratosis | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
| Erythema | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Skin exfoliation | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Skin mass | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 |
| Vascular disorders | ||||||||||||
| Hot flush | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 1/15 (6.7%) | 1 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Cyanosis | 0/15 (0%) | 0 | 1/14 (7.1%) | 1 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 |
| Peripheral venous disease | 1/15 (6.7%) | 1 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/22 (4.5%) | 1 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 |
| Hypotension | 0/15 (0%) | 0 | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | UCB |
|---|---|
| Organization | Cares |
| Phone | 001-844-599-2273 |
| UCBCares@ucb.com |
Responsible Party:
Ra Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT03315130
Other Study ID Numbers:
- RA101495-02.201
First Posted:
Oct 19, 2017
Last Update Posted:
Jul 27, 2022
Last Verified:
Jul 1, 2022