Trial Outcomes & Findings for A Study Evaluating the Safety and Efficacy of Rituximab in Patients With Myasthenia Gravis (NCT NCT02950155)

Last Updated: 2024-10-26

Results Overview

The Quantitative Myasthenia Gravis (QMG) score is a physician rated disease activity score that ranges from 0 to 39, where lower indicates better outcome. QMG was measured at 16 weeks under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors. Patients meeting the primary outcome had a QMG score of 4 or less whilst also requiring a daily oral Prednisolone dose of 10 mg or less.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

47 participants

Primary outcome timeframe

16 weeks

Results posted on

2024-10-26

Participant Flow

Between October 16th, 2016, and March 2nd, 2020, 87 potentially eligible patients were screened at 7 Swedish neurology clinics (5 university hospitals, 2 regional hospitals). 47 fulfilled inclusion and exclusion criteria and provided informed consent to participation.

All included participants received study drug

Participant milestones

Participant milestones
Measure	Rituximab A single intravenous infusion at a dose of 500 mg of Mabthera/Rituximab in Sodium Chloride solution.	Placebo A single intravenous infusion with sodium chloride solution in infusion bag matched to active treatment.
Overall Study STARTED	25	22
Overall Study COMPLETED	25	22
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab n=25 Participants A single infusion at a dose of 500 mg of Mabthera/Rituximab in Sodium Chloride solution.	Sodium Chloride Solution n=22 Participants A single infusion with sodium chloride solution in infusion bag matched to active treatment.	Total n=47 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=25 Participants	0 Participants n=22 Participants	0 Participants n=47 Participants
Age, Categorical Between 18 and 65 years	15 Participants n=25 Participants	14 Participants n=22 Participants	29 Participants n=47 Participants
Age, Categorical >=65 years	10 Participants n=25 Participants	8 Participants n=22 Participants	18 Participants n=47 Participants
Age, Continuous	67.4 years STANDARD_DEVIATION 13.4 • n=25 Participants	58.0 years STANDARD_DEVIATION 18.6 • n=22 Participants	63.0 years STANDARD_DEVIATION 16.6 • n=47 Participants
Sex: Female, Male Female	7 Participants n=25 Participants	7 Participants n=22 Participants	14 Participants n=47 Participants
Sex: Female, Male Male	18 Participants n=25 Participants	15 Participants n=22 Participants	33 Participants n=47 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Sweden	25 participants n=25 Participants	22 participants n=22 Participants	47 participants n=47 Participants
Body mass index	27.5 kg/m^2 STANDARD_DEVIATION 3.7 • n=25 Participants	27.6 kg/m^2 STANDARD_DEVIATION 5.7 • n=22 Participants	27.5 kg/m^2 STANDARD_DEVIATION 4.7 • n=47 Participants
Concentration of acetylcholine receptor antibodies	22.7 nmol/L STANDARD_DEVIATION 19.3 • n=25 Participants	70.7 nmol/L STANDARD_DEVIATION 117 • n=22 Participants	46.7 nmol/L STANDARD_DEVIATION 86.5 • n=47 Participants
Time since onset of generalized symptoms of myasthenia gravis	132.4 days STANDARD_DEVIATION 91.5 • n=25 Participants	143.0 days STANDARD_DEVIATION 93.3 • n=22 Participants	137.4 days STANDARD_DEVIATION 91.5 • n=47 Participants
Ocular symptoms prior to generalized symptoms of myasthenia gravis	4 participants n=25 Participants	2 participants n=22 Participants	6 participants n=47 Participants
Quantitative Myasthenia Gravis score	9.4 units on a scale STANDARD_DEVIATION 4.5 • n=25 Participants	9.3 units on a scale STANDARD_DEVIATION 4.5 • n=22 Participants	9.4 units on a scale STANDARD_DEVIATION 4.4 • n=47 Participants
Myasthenia Gravis Quality of Life questionnaire score	20.1 units on a scale STANDARD_DEVIATION 11.0 • n=25 Participants	22.2 units on a scale STANDARD_DEVIATION 12.8 • n=22 Participants	21.1 units on a scale STANDARD_DEVIATION 11.8 • n=47 Participants
Myasthenia Gravis Activities of Daily Living score	5.1 units on a scale STANDARD_DEVIATION 3.2 • n=25 Participants	4.5 units on a scale STANDARD_DEVIATION 2.7 • n=22 Participants	4.9 units on a scale STANDARD_DEVIATION 2.9 • n=47 Participants
Prednisolone	16 Participants n=25 Participants	12 Participants n=22 Participants	28 Participants n=47 Participants
Dose of Prednisolone (mg/day)	22.5 mg/day STANDARD_DEVIATION 10.8 • n=16 Participants • Average daily dose of Prednisolone for patients treated at baseline.	20.8 mg/day STANDARD_DEVIATION 9.0 • n=12 Participants • Average daily dose of Prednisolone for patients treated at baseline.	21.8 mg/day STANDARD_DEVIATION 9.9 • n=28 Participants • Average daily dose of Prednisolone for patients treated at baseline.
Intravenous immunoglobulins prior to baseline	8 Participants n=25 Participants	8 Participants n=22 Participants	16 Participants n=47 Participants
Plasmapheresis prior to baseline	1 Participants n=25 Participants	0 Participants n=22 Participants	1 Participants n=47 Participants
Early-onset myasthenia gravis	2 Participants n=25 Participants	7 Participants n=22 Participants	9 Participants n=47 Participants

PRIMARY outcome

Timeframe: 16 weeks

Population: Missing data, rituximab=1, placebo=1

Outcome measures

Outcome measures
Measure	Rituximab n=24 Participants A single infusion at a dose of 500 mg of Mabthera/Rituximab in Sodium Chloride solution.	Sodium Chloride Solution n=21 Participants A single infusion with sodium chloride solution in infusion bag matched to active treatment.
Percentage of Patients With Quantitative MG Score (QMG) Score ≤ 4 and a Daily Prednisolon Dose of ≤ 10mg at 16 Weeks After Administration of Study Drug/Placebo.	17 Participants	6 Participants

SECONDARY outcome

Timeframe: 24 weeks

Population: censured patients, rituximab=2, placebo=9

The Quantitative Myasthenia Gravis (QMG) score is a physician rated disease activity score that ranges from 0 to 39, where lower indicates better outcome. QMG was measured under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors. Change in QMG scores between the two time points was compared between groups.

Outcome measures

Outcome measures
Measure	Rituximab n=23 Participants A single infusion at a dose of 500 mg of Mabthera/Rituximab in Sodium Chloride solution.	Sodium Chloride Solution n=13 Participants A single infusion with sodium chloride solution in infusion bag matched to active treatment.
Change in QMG Score From Week 0 to Week 24 After Administration of Study Drug/Placebo.	-6.9 change in score points Standard Deviation 5.6	-5.8 change in score points Standard Deviation 4.6

SECONDARY outcome

Timeframe: 16 weeks

Population: censured patients, rituximab=3, placebo=7

The Myasthenia Gravis Activities of Daily Living (MG-ADL) score is a patient rated disease activity score that ranges from 0 to 24, where lower indicates better outcome. MG-ADL was assessed at 16 weeks under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors. Change in MG-ADL scores between the two time points was compared between groups.

Outcome measures

Outcome measures
Measure	Rituximab n=22 Participants A single infusion at a dose of 500 mg of Mabthera/Rituximab in Sodium Chloride solution.	Sodium Chloride Solution n=15 Participants A single infusion with sodium chloride solution in infusion bag matched to active treatment.
Change in Myasthenia Gravis Activities of Daily Living (MG-ADL) Score From Week 0 to Week 16 After Administration of Study Drug/Placebo	-1.7 change in score points Standard Deviation 2.5	-0.5 change in score points Standard Deviation 3.6

SECONDARY outcome

Timeframe: 16 weeks

Population: censured patients, rituximab=3, placebo=7

The Myasthenia Quality of Life (QoL) score is a patient rated quality of life score that ranges from 0 to 60, where lower indicates better outcome. Change in MG-QoL scores between the two time points was compared between groups. .

Outcome measures

Outcome measures
Measure	Rituximab n=22 Participants A single infusion at a dose of 500 mg of Mabthera/Rituximab in Sodium Chloride solution.	Sodium Chloride Solution n=15 Participants A single infusion with sodium chloride solution in infusion bag matched to active treatment.
Change in Myasthenia Gravis Quality of Life (QoL) Score From Week 0 to Week 16 After Administration of Study Drug/Placebo.	-9.2 change in score points Standard Deviation 9.2	-7.0 change in score points Standard Deviation 9.3

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 weeks

Population: missing data, rituximab=0, placebo=1

The Quantitative Myasthenia Gravis (QMG) score is a physician rated disease activity score that ranges from 0 to 39, where lower indicates better outcome. QMG was measured at 24 weeks under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors. Patients meeting the primary outcome had a QMG score of 4 or less whilst also requiring a daily oral Prednisolone dose of 10 mg or less.

Outcome measures

Outcome measures
Measure	Rituximab n=25 Participants A single infusion at a dose of 500 mg of Mabthera/Rituximab in Sodium Chloride solution.	Sodium Chloride Solution n=21 Participants A single infusion with sodium chloride solution in infusion bag matched to active treatment.
Percentage of Patients With Quantitative MG Ascore (QMG) Score ≤ 4 and a Daily Prednisolon Dose of ≤ 10mg at 24 Weeks After Administration of Study Drug/Placebo.	18 Participants	8 Participants

Adverse Events

Rituximab

Serious events: 5 serious events

Other events: 21 other events

Deaths: 1 deaths

Sodium Chloride Solution

Serious events: 4 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rituximab n=25 participants at risk A single infusion at a dose of 500 mg of Mabthera/Rituximab in Sodium Chloride solution.	Sodium Chloride Solution n=22 participants at risk A single infusion with sodium chloride solution in infusion bag matched to active treatment.
Blood and lymphatic system disorders Anemia	0.00% 0/25 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	4.5% 1/22 • Number of events 1 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Infections and infestations Pneumonia	0.00% 0/25 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	4.5% 1/22 • Number of events 1 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Infections and infestations Septicaemia	0.00% 0/25 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	4.5% 1/22 • Number of events 1 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Nervous system disorders Nausea	4.0% 1/25 • Number of events 1 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	0.00% 0/22 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Gastrointestinal disorders Ileus	4.0% 1/25 • Number of events 1 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	0.00% 0/22 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Cardiac disorders Chest pain	8.0% 2/25 • Number of events 2 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	0.00% 0/22 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Cardiac disorders Asystole	0.00% 0/25 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	4.5% 1/22 • Number of events 2 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Musculoskeletal and connective tissue disorders Vertebral compression fracture	4.0% 1/25 • Number of events 3 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	0.00% 0/22 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Cardiac disorders Syncope	4.0% 1/25 • Number of events 1 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	0.00% 0/22 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thymoma	0.00% 0/25 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	4.5% 1/22 • Number of events 1 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).

Other adverse events

Additional Information

Prof. Fredrik Piehl

Karolinska Institutet

Phone: +46 736718101

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Rituximab n=25 participants at risk A single infusion at a dose of 500 mg of Mabthera/Rituximab in Sodium Chloride solution.	Sodium Chloride Solution n=22 participants at risk A single infusion with sodium chloride solution in infusion bag matched to active treatment.
Skin and subcutaneous tissue disorders Rash	8.0% 2/25 • Number of events 2 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	18.2% 4/22 • Number of events 4 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Skin and subcutaneous tissue disorders Allergic reaction	12.0% 3/25 • Number of events 3 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	9.1% 2/22 • Number of events 2 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Gastrointestinal disorders Dry mouth	8.0% 2/25 • Number of events 2 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	0.00% 0/22 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Cardiac disorders Arrythmia	0.00% 0/25 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	9.1% 2/22 • Number of events 2 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Infections and infestations Upper respiratory infection	24.0% 6/25 • Number of events 7 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	36.4% 8/22 • Number of events 10 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Eye disorders Conjunctivitis	8.0% 2/25 • Number of events 2 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	0.00% 0/22 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Infections and infestations Fever of unknown cause	8.0% 2/25 • Number of events 2 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	0.00% 0/22 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Gastrointestinal disorders Nausea	8.0% 2/25 • Number of events 3 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	9.1% 2/22 • Number of events 2 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Gastrointestinal disorders Diarrhea	20.0% 5/25 • Number of events 5 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	9.1% 2/22 • Number of events 2 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Gastrointestinal disorders Rectal bleeding	8.0% 2/25 • Number of events 2 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	0.00% 0/22 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
General disorders Fatigue	8.0% 2/25 • Number of events 2 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	0.00% 0/22 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Blood and lymphatic system disorders Anemia	8.0% 2/25 • Number of events 2 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	0.00% 0/22 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Musculoskeletal and connective tissue disorders Muscle cramps	20.0% 5/25 • Number of events 5 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	4.5% 1/22 • Number of events 1 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Ear and labyrinth disorders Vertigo	8.0% 2/25 • Number of events 2 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	0.00% 0/22 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	32.0% 8/25 • Number of events 10 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	18.2% 4/22 • Number of events 4 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Renal and urinary disorders Urine leaks	8.0% 2/25 • Number of events 2 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	4.5% 1/22 • Number of events 1 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Renal and urinary disorders Kidney stone	0.00% 0/25 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	4.5% 1/22 • Number of events 2 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Renal and urinary disorders Urinary tract infection	8.0% 2/25 • Number of events 3 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	0.00% 0/22 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).
Injury, poisoning and procedural complications Bite from animal (dog)	8.0% 2/25 • Number of events 2 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).	0.00% 0/22 • 48 weeks, i.e. time from baseline to last follow up. The definitions described in clinicaltrials.gov are used with no exception. Information on potential adverse events was collected at each study visit (n=5) and telephone follow-ups (n=4).