First in Human Study of a Monoclonal Antibody (SOL-116) Targeting BSSL (Bile Salt-Stimulated Lipase), Single and Multiple Dose Parts

A Randomized, Double-Blind, Placebo-Controlled, First-in-Human Phase I Study Evaluating Safety, Tolerability and Pharmacokinetics of Single Ascending Doses of SOL-116 in Healthy Subjects and Patients With Rheumatoid Arthritis

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05576012

Enrollment

Registered

2022-10-12

Start date

2022-10-13

Completion date

2024-11-28

Last updated

2026-01-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rheumatoid Arthritis

Brief summary

This is a randomized, double-blind, placebo-controlled, first-in-human phase I study. It consists of a single ascending dose part in healthy subjects (Part 1) and in patients with rheumatoid arthritis (Part 2) as well as a multiple dose part in healthy subjects (Part 3). The study will collect information on pharmacokinetics, safety and tolerability.

Interventions

BIOLOGICALSOL-116

Participants will receive SC injection in a double-blind manner

BIOLOGICALPlacebo

Participants will receive SC injection in a double-blind manner

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Intervention model description

Part 1 single dose: Dose escalation in healthy subjects (up to 6 cohorts). Within each cohort, subjects will be randomized in a 3:1 ratio to receive either SOL-116 (n=6) or matching placebo (n=2) in a double-blind manner. Part 2 single dose in patients with rheumatoid arthritis (1 cohort). The patients will be randomized in a 3:1 ratio to receive either SOL-116 (n=6) or matching placebo (n=2) in a double-blind manner. Part 3 multiple dose in healthy subjects (1 or 2 cohorts). The subjects will be randomized in a 3:1 ratio to receive either SOL-116 (n=6) or matching placebo (n=2) in a double-blind manner.

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Yes

Inclusion criteria

1. Willing and able to give written informed consent for participation in the study and is willing and able to abide by the study restrictions. 2. Males and females aged between 18 and 65 years (inclusive) at Screening. For patients in the RA cohort, an age interval between 18 and 70 years (inclusive). 3. Normal clinically physical findings, apart from RA specific findings (including deviating laboratory values e.g., mild anaemia or swollen joints) for RA patients, including pulse rate, blood pressure, electrocardiogram (ECG), physical examination, and laboratory values (haematological/clinical chemistry) as judged by the Investigator. Healthy subjects must be negative for anti-CCP and have Rheumatoid Factor \<1.5 ULN at Screening. 4. For Parts 1 and 3, body mass index (BMI) between 19.0 and 30.0 kg/m2 and body weight between 50 to 100 kg (inclusive) at Screening. For Part 2, body weight between 50 to 120 kg (inclusive) at Screening. 5. Sexually active male patients participating in the study must use a barrier method of contraception (condom) and refrain from sperm donation during the study and for at least 150 days after last dosing if their female sexual partner is of childbearing potential. Acceptable methods of birth control for female partners of male subjects are: hormonal contraceptives (oral contraceptives, implant or injection), intrauterine device (placed at least 1 month before the start of the study). Surgical sterilization of male patients can be accepted as a form of birth control if the sterilization procedure took place at least 6 months prior to the start of the study. 6. Females of childbearing potential must during the study and for at least 230 days after last dosing utilise a method of contraception that can achieve a failure rate of less than 1% per year when used consistently and correctly (defined in study protocol). 7. Females of non-childbearing potential must fulfil one of the following: * Irreversibly surgically sterile i.e., hysterectomy, bilateral salpingectomy, the fallopian tubes have been blocked or sealed (sterilization), and bilateral oophorectomy. * Spontaneous amenorrhoea during the last 12 months prior to enrolment, and having follicle stimulating hormone (FSH) levels in the postmenopausal range (i.e. ≥ 30 mIU/mL) at Screening. The following inclusion criterion is only applicable for RA patients: 8. Fulfilling the 2010 American College of Rheumatology (ACR)/European Union League Against Rheumatism (EULAR) classification criteria for RA \[8\]. * Treatment with MTX for at least 12 weeks prior to treatment start and planned to continue with MTX during the study; if the MTX dose was changed during the 12-week period, such a patient may be included in the study based on Investigator judgement. * Patients naïve to biological disease modifying anti-rheumatic drug (bDMARD) or who are washed out (at least 5 half-lives) from such therapy before study drug dosing. * Patients naïve to conventional/targeted synthetic disease modifying anti-rheumatic drug (csDMARD/tsDMARD), except for MTX, or who are washed out since at least 12 weeks from such therapy before study drug dosing. * Use of oral glucocorticosteroids is allowed if equivalent to ≤5 mg/day of prednisolone on a stable dose for a least 4 weeks prior to dosing (Day 1) and expected to remain on that dose level for at least 4 weeks after dosing (Day 1).

Exclusion criteria

1. History of any clinically significant acute inflammatory joint disease (for the RA cohort; other than RA). 2. Any chronic or long-lasting disease which may interfere with the study objectives or jeopardise the safety of the subjects/patients as judged by the Investigator or responsible physician (for the RA cohort; other than RA). 3. Ongoing infection on Day-1. 4. Serious infection treated with antibiotics and evaluated by physician in the past 14 days prior to Day -1. 5. Current treatment with heparin products. 6. Use of any prescription or non-prescription drugs (excluding paracetamol, hormonal contraceptives), antacids, herbal, and dietary supplements (including St John's Wort) within 14 days (or 28 days if the drug is a potential hepatic enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study drug for healthy subjects and within 4 weeks prior to the first dose of study drug for RA patients, unless in the opinion of the Investigator the medication will not interfere with the study procedures or compromise subject/patient safety. In RA patients, MTX and folic acid use are exempted. 7. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥ 2.0 times upper limit of normal (ULN); alkaline phosphatase and bilirubin ≥ 1.5 times the ULN at Screening or on Day -1. At screening, these assessments may be repeated once, at the discretion of the Investigator. 8. Serum creatinine \> 1.5 times the ULN or eGFR \<60 at Screening or on Day -1 (for Part 1 and Part 3). Estimated glomerular filtration rat (eGFR) \<60 at Screening or on Day -1 (for Part 2). At Screening, these assessments may be repeated once, at the discretion of the Investigator. 9. Subjects/patients who have experienced surgery within 6 months of the screening visit that could negatively impact on the subject's/patient's participation in the opinion of a Principal Investigator or responsible physician. 10. High blood pressure at Screening or on Day -1, judged as clinically relevant by a Principal Investigator or responsible physician. A repeat test may be performed. 11. Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (anti-HCV) at Screening. 12. Having evidence of active TB or latent TB at Screening as assessed by chest X-ray (RA patients only) and/or by QuantiFERON®-test. Applicable for RA patients only: in case of rescreening within three months after Screening, negative results from the initial chest X-ray and/or QuantiFERON®-test performed during Screening do not need to be repeated. 13. Subjects/patients who are currently enrolled in or have recently participated in another interventional clinical study defined as having received the last intervention within 90 days or 5 half-lives of the study drug (whichever is longer) prior to dosing (Parts 1 and 2) vs. prior to first dosing (Part 3) of the study drug. 14. History or known hypersensitivity or allergy, or any form of allergic reactions to any excipients in the study drug or to humanized or murine monoclonal antibodies (or immunoglobulins). 15. Receipt of a vaccine within 4 weeks (COVID-19 vaccine within 6 weeks) prior to dosing and/or the intention to receive a vaccine during the study. Deviation from this should be judged by the Investigator and in dialogue with the Sponsor. 16. Recent confirmed COVID-19 infection, with less than 6 weeks between recovery and dosing of study drug. 17. Blood or plasma donation within 3 months of enrolment. 18. Positive urine drug screen or alcohol test at Screening or on Day -1. 19. History of drug or alcohol abuse, at the discretion of the Investigator, within past 12 months prior to Screening. 20. The subject currently smokes or uses nicotine-containing products. Former smokers will be eligible, provided they have not smoked for at least 1 month prior to Screening. Positive cotinine test results at Screening or on Day -1 are reason for exclusion. Such positive test results can be repeated once to exclude environmental influence on the subject. 21. A positive pregnancy test or lactation at Screening or on Day -1. The following

Design outcomes

Primary

Measure	Time frame	Description
Safety and Tolerability: Vital Signs - Blood Pressure	From screening through study completion: screening, pre-dose, 1, 4, 24, 48, 72 hours and Days 14, 21, 49 and 90 (cohorts 1-5 and 7). For cohort 6: screening, pre-dose, 1, 4, 24, 72 hours and Days 8, 29, 57, 85, 86, 88, 92,169	Number of clinically significant abnormal findings - Blood pressure
Safety and Tolerability: Adverse Events	From screening through study completion, day 90 (Cohorts 1-5 and 7) vs. day 169 (Cohort 6)	Number of adverse events (AEs); (assessed as related and non-related)
Safety and Tolerability: Injection Site Reactions	From screening through study completion, day 90 (Cohorts 1-5 and 7) vs. day 169 (Cohort 6)	Number of injection site reactions (dryness, redness, swelling, pain/tenderness and itching)
Safety and Tolerability: Clinical Laboratory Evaluations	From screening through study completion, day 90 (Cohorts 1-5 and 7) vs. day 169 (Cohort 6)	Number of clinically significant laboratory abnormalities
Safety and Tolerability: Immune Reactions	From screening through study completion, day 90 (Cohorts 1-5 and 7) vs. day 169 (Cohort 6)	Number of immune reactions (hypersensitivity, cytokine release syndrome, immunogenicity)
Safety and Tolerability: Electrocardiogram (ECG)	From screening through study completion, day 90 (Cohorts 1-5 and 7) vs. day 169 (Cohort 6)	Number of clinically significant abnormal findings recorded by investigator based on HR, PR, QRS and QT values of ECG
Safety and Tolerability: Vital Signs - Temporal Body Temperature	From screening through study completion: screening, pre-dose, 1, 4, 24, 48, 72 hours and Days 14, 21, 49 and 90 (cohorts 1-5 and 7). For cohort 6: screening, pre-dose, 1, 4, 24, 72 hours and Days 8, 29, 57, 85, 86, 88, 92,169	Number of clinically significant abnormal findings - Temporal Body Temperature
Safety and Tolerability: Vital Signs - Pulse Rate	From screening through study completion: screening, pre-dose, 1, 4, 24, 48, 72 hours and Days 14, 21, 49 and 90 (cohorts 1-5 and 7). For cohort 6: screening, pre-dose, 1, 4, 24, 72 hours and Days 8, 29, 57, 85, 86, 88, 92,169	Number of clinically significant abnormal findings - Pulse rate

Secondary

Measure	Time frame	Description
PK Parameters for SOL-116: AUC0-inf	Cohorts 1-5 and 7: Pre-dose, 1h, 4h, 8h, days 2, 3, 4, 8, 14, 21, 35, 49, 63 and 90. Cohort 6: Pre-dose, 4h, days 2, 4, 8, 11, 15, 29, 57, 85, 86, 88, 92, 95, 99, 113, 140, 154, 169	Area under the concentration-time curve up to infinite time
PK Parameters for SOL-116: AUC0-t	Cohorts 1-5 and 7: Pre-dose, 1h, 4h, 8h, days 2, 3, 4, 8, 14, 21, 35, 49, 63 and 90. Cohort 6: Pre-dose, 4h, days 2, 4, 8, 11, 15, 29, 57, 85, 86, 88, 92, 95, 99, 113, 140, 154, 169	Area under the concentration-time curve up to the last measurable concentration
PK Parameters for SOL-116: Cmax	Cohorts 1-5 and 7: Pre-dose, 1h, 4h, 8h, days 2, 3, 4, 8, 14, 21, 35, 49, 63 and 90. Cohort 6: Pre-dose, 4h, days 2, 4, 8, 11, 15, 29, 57, 85, 86, 88, 92, 95, 99, 113, 140, 154, 169	Maximal observed concentration (Cmax)
PK Parameters for SOL-116: Tmax	Cohorts 1-5 and 7: Pre-dose, 1h, 4h, 8h, days 2, 3, 4, 8, 14, 21, 35, 49, 63 and 90. Cohort 6: Pre-dose, 4h, days 2, 4, 8, 11, 15, 29, 57, 85, 86, 88, 92, 95, 99, 113, 140, 154, 169	Time to Cmax
PK Parameters for SOL-116: T1/2	Cohorts 1-5 and 7: Pre-dose, 1h, 4h, 8h, days 2, 3, 4, 8, 14, 21, 35, 49, 63 and 90. Cohort 6: Pre-dose, 4h, days 2, 4, 8, 11, 15, 29, 57, 85, 86, 88, 92, 95, 99, 113, 140, 154, 169	Outcome measure: Terminal elimination half-life
PK Parameters for SOL-116: Vz/F	Cohorts 1-5 and 7: Pre-dose, 1h, 4h, 8h, days 2, 3, 4, 8, 14, 21, 35, 49, 63 and 90. Cohort 6: Pre-dose, 4h, days 2, 4, 8, 11, 15, 29, 57, 85, 86, 88, 92, 95, 99, 113, 140, 154, 169	Apparent volume of distribution following extravascular administration
PK Parameters for SOL-116: CL/F	Cohorts 1-5 and 7: Pre-dose, 1h, 4h, 8h, days 2, 3, 4, 8, 14, 21, 35, 49, 63 and 90. Cohort 6: Pre-dose, 4h, days 2, 4, 8, 11, 15, 29, 57, 85, 86, 88, 92, 95, 99, 113, 140, 154, 169	Apparent total body clearance following extravascular administration
Immunogenicity Parameters: ADA	Cohorts 1-5 and 7: Pre-dose, 4h, days 8, 21, 49 and 90. Cohort 6: Pre-dose, days 29, 57, 85, 113 and 169.	Number of samples with detectable ADA (anti-drug antibodies)

Countries

Netherlands

Participant flow

Pre-assignment details

This is a phase I study that covers three parts: ascending single doses in healthy subjects, single dose in patients and multiple doses in healthy subjects; each cohort is small 6 active + 2 placebo subjects. The complete results are found in the Clinical Study Report. In section Results Participant Flow, detailed design, dose levels, number of subjects are shown.

Participants by arm

Arm	Count
Cohort 1 (Single Dose) 0.075 mg/kg SOL-116 (healthy subjects)	6
Cohort 2 (Single Dose) 0.225 mg/kg SOL-116 (healthy subjects)	6
Cohort 3 (Single Dose) 0.675 mg/kg SOL-116 (healthy subjects)	6
Cohort 4 (Single Dose) 2.025 mg/kg SOL-116 (healthy subjects)	6
Cohort 5 (Single Dose) 6.075 mg/kg SOL-116 (healthy subjects)	6
Cohort 6 (Multiple Doses) 3.0 mg/kg SOL-116 x 4 (healthy subjects)	6
Cohort 7 (Single Dose) 2.025 mg/kg SOL-116 (patients with rheumatoid arthritis)	6
Placebo (Coh 1-5) Placebo (Cohorts 1-5)	10
Placebo (Cohort 6) Placebo (Cohorts 6)	2
Placebo (Cohort 7) Placebo (Cohorts 7)	2
Total	56

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009
Overall Study	Physician Decision	0	0	0	0	0	0	0	0	1	0

Baseline characteristics

Characteristic	Total	Cohort 1 (Single Dose)	Cohort 3 (Single Dose)	Cohort 4 (Single Dose)	Cohort 5 (Single Dose)	Cohort 2 (Single Dose)	Cohort 6 (Multiple Doses)	Cohort 7 (Single Dose)	Placebo (Coh 1-5)	Placebo (Cohort 6)	Placebo (Cohort 7)
Age, Continuous	50.0 years STANDARD_DEVIATION 14.4	46.7 years STANDARD_DEVIATION 19.2	42.8 years STANDARD_DEVIATION 18.3	44.2 years STANDARD_DEVIATION 14.4	45.5 years STANDARD_DEVIATION 10.7	44.8 years STANDARD_DEVIATION 17.1	58.2 years STANDARD_DEVIATION 3.7	58.2 years STANDARD_DEVIATION 11.5	52.0 years STANDARD_DEVIATION 14.3	57.5 years STANDARD_DEVIATION 0.7	63.5 years STANDARD_DEVIATION 0.7
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants	0 Participants	1 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	52 Participants	6 Participants	5 Participants	6 Participants	4 Participants	6 Participants	6 Participants	6 Participants	9 Participants	2 Participants	2 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	6 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants	2 Participants	1 Participants	0 Participants
Race (NIH/OMB) Black or African American	3 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	46 Participants	5 Participants	5 Participants	5 Participants	5 Participants	6 Participants	5 Participants	5 Participants	7 Participants	1 Participants	2 Participants
Region of Enrollment Netherlands	56 participants	6 participants	6 participants	6 participants	6 participants	6 participants	6 participants	6 participants	10 participants	2 participants	2 participants
Sex: Female, Male Female	23 Participants	2 Participants	1 Participants	2 Participants	4 Participants	3 Participants	4 Participants	3 Participants	3 Participants	0 Participants	1 Participants
Sex: Female, Male Male	33 Participants	4 Participants	5 Participants	4 Participants	2 Participants	3 Participants	2 Participants	3 Participants	7 Participants	2 Participants	1 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk
deaths Total, all-cause mortality	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 10	0 / 2	0 / 2
other Total, other adverse events	4 / 6	5 / 6	3 / 6	5 / 6	3 / 6	5 / 6	6 / 6	6 / 10	2 / 2	2 / 2
serious Total, serious adverse events	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 10	1 / 2	0 / 2

Outcome results

Primary

Safety and Tolerability: Adverse Events

Number of adverse events (AEs); (assessed as related and non-related)

Time frame: From screening through study completion, day 90 (Cohorts 1-5 and 7) vs. day 169 (Cohort 6)

Population: Safety set

Arm	Measure	Value (NUMBER)
Cohort 1 (Single Dose)	Safety and Tolerability: Adverse Events	7 number of events
Cohort 2 (Single Dose)	Safety and Tolerability: Adverse Events	9 number of events
Cohort 3 (Single Dose)	Safety and Tolerability: Adverse Events	8 number of events
Cohort 4 (Single Dose)	Safety and Tolerability: Adverse Events	8 number of events
Cohort 5 (Single Dose)	Safety and Tolerability: Adverse Events	4 number of events
Cohort 6 (Multiple Doses)	Safety and Tolerability: Adverse Events	24 number of events
Cohort 7 (Single Dose)	Safety and Tolerability: Adverse Events	28 number of events
Placebo (Cohorts 1-5)	Safety and Tolerability: Adverse Events	8 number of events
Placebo (Cohort 6)	Safety and Tolerability: Adverse Events	3 number of events
Placebo (Cohort 7)	Safety and Tolerability: Adverse Events	4 number of events

Primary

Safety and Tolerability: Clinical Laboratory Evaluations

Number of clinically significant laboratory abnormalities

Time frame: From screening through study completion, day 90 (Cohorts 1-5 and 7) vs. day 169 (Cohort 6)

Population: Safety set

Arm	Measure	Value (COUNT_OF_UNITS)
Cohort 1 (Single Dose)	Safety and Tolerability: Clinical Laboratory Evaluations	0 samples
Cohort 2 (Single Dose)	Safety and Tolerability: Clinical Laboratory Evaluations	0 samples
Cohort 3 (Single Dose)	Safety and Tolerability: Clinical Laboratory Evaluations	0 samples
Cohort 4 (Single Dose)	Safety and Tolerability: Clinical Laboratory Evaluations	0 samples
Cohort 5 (Single Dose)	Safety and Tolerability: Clinical Laboratory Evaluations	0 samples
Cohort 6 (Multiple Doses)	Safety and Tolerability: Clinical Laboratory Evaluations	0 samples
Cohort 7 (Single Dose)	Safety and Tolerability: Clinical Laboratory Evaluations	0 samples
Placebo (Cohorts 1-5)	Safety and Tolerability: Clinical Laboratory Evaluations	0 samples
Placebo (Cohort 6)	Safety and Tolerability: Clinical Laboratory Evaluations	0 samples
Placebo (Cohort 7)	Safety and Tolerability: Clinical Laboratory Evaluations	0 samples

Primary

Safety and Tolerability: Electrocardiogram (ECG)

Number of clinically significant abnormal findings recorded by investigator based on HR, PR, QRS and QT values of ECG

Time frame: From screening through study completion, day 90 (Cohorts 1-5 and 7) vs. day 169 (Cohort 6)

Population: Safety set

Arm	Measure	Value (NUMBER)
Cohort 1 (Single Dose)	Safety and Tolerability: Electrocardiogram (ECG)	0 events
Cohort 2 (Single Dose)	Safety and Tolerability: Electrocardiogram (ECG)	0 events
Cohort 3 (Single Dose)	Safety and Tolerability: Electrocardiogram (ECG)	0 events
Cohort 4 (Single Dose)	Safety and Tolerability: Electrocardiogram (ECG)	0 events
Cohort 5 (Single Dose)	Safety and Tolerability: Electrocardiogram (ECG)	0 events
Cohort 6 (Multiple Doses)	Safety and Tolerability: Electrocardiogram (ECG)	0 events
Cohort 7 (Single Dose)	Safety and Tolerability: Electrocardiogram (ECG)	0 events
Placebo (Cohorts 1-5)	Safety and Tolerability: Electrocardiogram (ECG)	0 events
Placebo (Cohort 6)	Safety and Tolerability: Electrocardiogram (ECG)	0 events
Placebo (Cohort 7)	Safety and Tolerability: Electrocardiogram (ECG)	0 events

Primary

Safety and Tolerability: Immune Reactions

Number of immune reactions (hypersensitivity, cytokine release syndrome, immunogenicity)

Time frame: From screening through study completion, day 90 (Cohorts 1-5 and 7) vs. day 169 (Cohort 6)

Population: Safety set

Arm	Measure	Value (NUMBER)
Cohort 1 (Single Dose)	Safety and Tolerability: Immune Reactions	0 events
Cohort 2 (Single Dose)	Safety and Tolerability: Immune Reactions	0 events
Cohort 3 (Single Dose)	Safety and Tolerability: Immune Reactions	0 events
Cohort 4 (Single Dose)	Safety and Tolerability: Immune Reactions	0 events
Cohort 5 (Single Dose)	Safety and Tolerability: Immune Reactions	0 events
Cohort 6 (Multiple Doses)	Safety and Tolerability: Immune Reactions	0 events
Cohort 7 (Single Dose)	Safety and Tolerability: Immune Reactions	0 events
Placebo (Cohorts 1-5)	Safety and Tolerability: Immune Reactions	0 events
Placebo (Cohort 6)	Safety and Tolerability: Immune Reactions	0 events
Placebo (Cohort 7)	Safety and Tolerability: Immune Reactions	0 events

Primary

Safety and Tolerability: Injection Site Reactions

Number of injection site reactions (dryness, redness, swelling, pain/tenderness and itching)

Time frame: From screening through study completion, day 90 (Cohorts 1-5 and 7) vs. day 169 (Cohort 6)

Population: Safety set

Arm	Measure	Value (NUMBER)
Cohort 1 (Single Dose)	Safety and Tolerability: Injection Site Reactions	0 number of events
Cohort 2 (Single Dose)	Safety and Tolerability: Injection Site Reactions	0 number of events
Cohort 3 (Single Dose)	Safety and Tolerability: Injection Site Reactions	1 number of events
Cohort 4 (Single Dose)	Safety and Tolerability: Injection Site Reactions	4 number of events
Cohort 5 (Single Dose)	Safety and Tolerability: Injection Site Reactions	3 number of events
Cohort 6 (Multiple Doses)	Safety and Tolerability: Injection Site Reactions	0 number of events
Cohort 7 (Single Dose)	Safety and Tolerability: Injection Site Reactions	3 number of events
Placebo (Cohorts 1-5)	Safety and Tolerability: Injection Site Reactions	2 number of events
Placebo (Cohort 6)	Safety and Tolerability: Injection Site Reactions	0 number of events
Placebo (Cohort 7)	Safety and Tolerability: Injection Site Reactions	0 number of events

Primary

Safety and Tolerability: Vital Signs - Blood Pressure

Number of clinically significant abnormal findings - Blood pressure

Time frame: From screening through study completion: screening, pre-dose, 1, 4, 24, 48, 72 hours and Days 14, 21, 49 and 90 (cohorts 1-5 and 7). For cohort 6: screening, pre-dose, 1, 4, 24, 72 hours and Days 8, 29, 57, 85, 86, 88, 92,169

Population: Safety set

Arm	Measure	Value (NUMBER)
Cohort 1 (Single Dose)	Safety and Tolerability: Vital Signs - Blood Pressure	0 events
Cohort 2 (Single Dose)	Safety and Tolerability: Vital Signs - Blood Pressure	0 events
Cohort 3 (Single Dose)	Safety and Tolerability: Vital Signs - Blood Pressure	0 events
Cohort 4 (Single Dose)	Safety and Tolerability: Vital Signs - Blood Pressure	0 events
Cohort 5 (Single Dose)	Safety and Tolerability: Vital Signs - Blood Pressure	0 events
Cohort 6 (Multiple Doses)	Safety and Tolerability: Vital Signs - Blood Pressure	0 events
Cohort 7 (Single Dose)	Safety and Tolerability: Vital Signs - Blood Pressure	0 events
Placebo (Cohorts 1-5)	Safety and Tolerability: Vital Signs - Blood Pressure	0 events
Placebo (Cohort 6)	Safety and Tolerability: Vital Signs - Blood Pressure	0 events
Placebo (Cohort 7)	Safety and Tolerability: Vital Signs - Blood Pressure	0 events

Primary

Safety and Tolerability: Vital Signs - Pulse Rate

Number of clinically significant abnormal findings - Pulse rate

Population: Safety set

Arm	Measure	Value (NUMBER)
Cohort 1 (Single Dose)	Safety and Tolerability: Vital Signs - Pulse Rate	0 events
Cohort 2 (Single Dose)	Safety and Tolerability: Vital Signs - Pulse Rate	0 events
Cohort 3 (Single Dose)	Safety and Tolerability: Vital Signs - Pulse Rate	0 events
Cohort 4 (Single Dose)	Safety and Tolerability: Vital Signs - Pulse Rate	0 events
Cohort 5 (Single Dose)	Safety and Tolerability: Vital Signs - Pulse Rate	0 events
Cohort 6 (Multiple Doses)	Safety and Tolerability: Vital Signs - Pulse Rate	0 events
Cohort 7 (Single Dose)	Safety and Tolerability: Vital Signs - Pulse Rate	0 events
Placebo (Cohorts 1-5)	Safety and Tolerability: Vital Signs - Pulse Rate	0 events
Placebo (Cohort 6)	Safety and Tolerability: Vital Signs - Pulse Rate	0 events
Placebo (Cohort 7)	Safety and Tolerability: Vital Signs - Pulse Rate	0 events

Primary

Safety and Tolerability: Vital Signs - Temporal Body Temperature

Number of clinically significant abnormal findings - Temporal Body Temperature

Population: Safety set

Arm	Measure	Value (NUMBER)
Cohort 1 (Single Dose)	Safety and Tolerability: Vital Signs - Temporal Body Temperature	0 events
Cohort 2 (Single Dose)	Safety and Tolerability: Vital Signs - Temporal Body Temperature	0 events
Cohort 3 (Single Dose)	Safety and Tolerability: Vital Signs - Temporal Body Temperature	0 events
Cohort 4 (Single Dose)	Safety and Tolerability: Vital Signs - Temporal Body Temperature	0 events
Cohort 5 (Single Dose)	Safety and Tolerability: Vital Signs - Temporal Body Temperature	0 events
Cohort 6 (Multiple Doses)	Safety and Tolerability: Vital Signs - Temporal Body Temperature	0 events
Cohort 7 (Single Dose)	Safety and Tolerability: Vital Signs - Temporal Body Temperature	0 events
Placebo (Cohorts 1-5)	Safety and Tolerability: Vital Signs - Temporal Body Temperature	0 events
Placebo (Cohort 6)	Safety and Tolerability: Vital Signs - Temporal Body Temperature	0 events
Placebo (Cohort 7)	Safety and Tolerability: Vital Signs - Temporal Body Temperature	0 events

Secondary

Immunogenicity Parameters: ADA

Number of samples with detectable ADA (anti-drug antibodies)

Time frame: Cohorts 1-5 and 7: Pre-dose, 4h, days 8, 21, 49 and 90. Cohort 6: Pre-dose, days 29, 57, 85, 113 and 169.

Population: Immunogenicity set

Arm	Measure	Value (NUMBER)
Cohort 1 (Single Dose)	Immunogenicity Parameters: ADA	0 number of samples
Cohort 2 (Single Dose)	Immunogenicity Parameters: ADA	0 number of samples
Cohort 3 (Single Dose)	Immunogenicity Parameters: ADA	0 number of samples
Cohort 4 (Single Dose)	Immunogenicity Parameters: ADA	0 number of samples
Cohort 5 (Single Dose)	Immunogenicity Parameters: ADA	0 number of samples
Cohort 6 (Multiple Doses)	Immunogenicity Parameters: ADA	0 number of samples
Cohort 7 (Single Dose)	Immunogenicity Parameters: ADA	1 number of samples
Placebo (Cohorts 1-5)	Immunogenicity Parameters: ADA	0 number of samples
Placebo (Cohort 6)	Immunogenicity Parameters: ADA	0 number of samples
Placebo (Cohort 7)	Immunogenicity Parameters: ADA	0 number of samples

Secondary