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

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Biological: SOL-116; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands
    • QPS Netherlands B.V.
  • Leiden, Netherlands
    • CHDR (Stichting Centre for Human Drug Research)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 exclusion criteria are only applicable for RA patients:

22. Intra-articular or systemic corticosteroid injection within 4 weeks prior to dosing.
23. Current or expected need of other immunosuppressant medication except MTX and/or intra-articular corticosteroid injections.
24. Known Gilbert's syndrome or Screening laboratory values indicating Gilbert's syndrome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SOL-116 single dose (Parts 1 and 2); multiple dose (Part 3) (SC administration)	Biological: SOL-116; Participants will receive SC injection in a double-blind manner
Placebo Comparator: Placebo single dose (Parts 1 and 2); multiple dose (Part 3) (SC administration)	Biological: Placebo; Participants will receive SC injection in a double-blind manner

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability: Adverse Events	Number of adverse events (AEs); (assessed as related and non-related)	From screening through study completion, day 90 (Cohorts 1-5 and 7) vs. day 169 (Cohort 6)
Safety and Tolerability: Injection Site Reactions	Number of injection site reactions (dryness, redness, swelling, pain/tenderness and itching)	From screening through study completion, day 90 (Cohorts 1-5 and 7) vs. day 169 (Cohort 6)
Safety and Tolerability: Clinical Laboratory Evaluations	Number of clinically significant laboratory abnormalities	From screening through study completion, day 90 (Cohorts 1-5 and 7) vs. day 169 (Cohort 6)
Safety and Tolerability: Immune Reactions	Number of immune reactions (hypersensitivity, cytokine release syndrome, immunogenicity)	From screening through study completion, day 90 (Cohorts 1-5 and 7) vs. day 169 (Cohort 6)
Safety and Tolerability: Electrocardiogram (ECG)	Number of clinically significant abnormal findings recorded by investigator based on HR, PR, QRS and QT values of ECG	From screening through study completion, day 90 (Cohorts 1-5 and 7) vs. day 169 (Cohort 6)
Safety and Tolerability: Vital Signs - Temporal Body Temperature	Number of clinically significant abnormal findings - 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
Safety and Tolerability: Vital Signs - Pulse Rate	Number of clinically significant abnormal findings - 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
Safety and Tolerability: Vital Signs - Blood Pressure	Number of clinically significant abnormal findings - 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK Parameters for SOL-116: AUC0-inf	Area under the concentration-time curve up to infinite time	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
PK Parameters for SOL-116: AUC0-t	Area under the concentration-time curve up to the last measurable concentration	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
PK Parameters for SOL-116: Cmax	Maximal observed concentration (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
PK Parameters for SOL-116: Tmax	Time to 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
PK Parameters for SOL-116: T1/2	Outcome measure: Terminal elimination half-life	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
PK Parameters for SOL-116: Vz/F	Apparent volume of distribution following extravascular administration	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
PK Parameters for SOL-116: CL/F	Apparent total body clearance following extravascular administration	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
Immunogenicity Parameters: ADA	Number of samples with detectable ADA (anti-drug antibodies)	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.

Collaborators and Investigators

• Sponsor: Lipum AB
• Collaborators: QPS Netherlands B.V.
• Investigators: Principal Investigator: Khalid Abd-Elaziz, MD, QPS Netherlands B.V.

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2022
• Primary Completion (Actual): November 28, 2024
• Study Completion (Actual): November 28, 2024

Study Registration Dates

• First Submitted: October 3, 2022
• First Submitted That Met QC Criteria: October 7, 2022
• First Posted (Actual): October 12, 2022

Study Record Updates

• Last Update Posted (Estimated): January 8, 2026
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Arthritis, Rheumatoid
• Other Study ID Numbers: LPM-116-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No