Single dosingPrimary objective:• To evaluate the safety and tolerability of single ascending doses of SOL-116 in healthy subjects and rheumatoid arthritis (RA) patients.Secondary objective:• To determine single dose pharmacokinetic (PK)…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Adverse events (type, frequency, severity, and relationship of adverse events
(AEs) to study drug treatment), clinical laboratory evaluations (including
blood haematology/plasma biochemistry analyses and urinalyses), immune
reactions, vital signs, electrocardiogram (ECG) and injection site reactions.
Secondary outcome
All parts
• PK of SOL-116 variables: area under the serum concentration-time from time
zero to infinity (AUC0-inf), AUC from time zero to time t of the last measured
concentration above the limit of quantification (AUC0-t), maximum observed
serum concentration (Cmax), time to Cmax (Tmax), terminal elimination half-life
(T1/2), apparent volume of distribution (Vz/F), apparent total body clearance
(CL/F) and dose proportionality after single dose (based on AUC and Cmax).
• Incidence and titre of anti-drug antibodies (ADA) to SOL-116.
Multiple dosing
• PK of SOL-116 variables for the last dose: area under the serum
concentration-time from time zero to the end of dosing interval (AUC0-tau),
maximum observed serum concentration (Cmax), time to Cmax (Tmax), minimum
observed serum concentration (Ctrough), average serum concentration (Cave),
apparent total body clearance at steady state (CLss/F), time to steady state,
accumulation ratio in Cmax and AUC0-tau
Background summary
RA is a chronic autoimmune inflammatory joint disease characterized by a
varying number of swollen, stiff and painful joints typically in hands and
feet, but any joint may be affected. With time, erosion of joints and bone
results in varying degree of disability and loss of quality of life.
The treatment of RA is still associated with high unmet medical need (4).
Synthetic disease-modifying antirheumatic drugs (sDMARDs) and steroids, which
are key in initial treatment of RA, are all associated with adverse effects
(AE) and thus intolerability (e.g., gastrointestinal, pulmonary, infectious and
hematologic AEs.
Given the preclinical data at hand (see below) and the new mechanism of action
targeting an alternative inflammatory pathway compared to the approved
products, it is believed that SOL-116 may demonstrate significant benefit in
patients not responding satisfactory, or responding transiently, to current
therapies, as well as those who suffer from serious adverse effects. The
candidate drug SOL-116 may be used as a standalone treatment, or in
combination with other treatments, including sDMARDs but also other bDMARDs to
reduce the risk of lost efficacy.
Study objective
Single dosing
Primary objective:
• To evaluate the safety and tolerability of single ascending doses of SOL-116
in healthy subjects and rheumatoid arthritis (RA) patients.
Secondary objective:
• To determine single dose pharmacokinetic (PK) characteristics of SOL-116 in
healthy subjects and RA patients.
• To assess the immunogenicity of SOL-116 after single SC doses in healthy
subjects and RA patients.
Multiple dosing
Primary objective:
• To evaluate the safety and tolerability of multiple dosing of SOL-116 in
healthy subjects.
Secondary objective:
• To determine multiple dose PK characteristics of SOL-116 in healthy subjects.
• To assess the immunogenicity of SOL-116 after multiple SC doses in healthy
subjects.
Study design
This is a randomised, double-blind, placebo-controlled phase 1, first-in-human
(FIH) study designed to evaluate the safety, tolerability and pharmacokinetics
(PK) of single subcutanous ascending doses of SOL-116 in healthy subjects and
adult patients with RA.
Intervention
SOL-116 (100 mg/mL) - subcutaneous administration or Matching placebo (saline
or vehicle) - subcutaneous administration
Study burden and risks
SOL-116 plasma concentrations in the planned single ascending dose (first in
human) study are predicted to be well below the levels where adverse effects
may start to develop. Patients participating in clinical trials must be closely
monitored for any adverse events, and laboratory, physical examination, ECG, or
vital signs abnormalities. As with all investigational compounds, the potential
exists for unanticipated serious or life threatening toxicities or adverse
events not predicted by the animal toxicology conducted to date. Investigators
should exercise vigilance in the monitoring of patients involved in this
clinical trial with SOL-116. The combined safety data from the pre-clinical
studies have not revealed any safety issues that would outweigh the expected
benefits. The planned study assessments are considered sufficient to meet the
scientific and medical goals for the study. Given the high medical need of
additional therapy with a novel mechanism of action it is therefore concluded
that the potential benefits from assessment of the scientific objectives in the
study outweigh the potential risks for the treated subjects.
Tvistevägen 48C
Umeå SE-907 36
SE
Tvistevägen 48C
Umeå SE-907 36
SE
Listed location countries
Age
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.
Such highly effective birth control methods include:
• combined (estrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation:
o oral
o intravaginal
o transdermal
• progestogen-only hormonal contraception associated with inhibition of
ovulation:
o oral
o injectable
o implantable
• intrauterine device (IUD)
• intrauterine hormone-releasing system (IUS)
• bilateral tubal occlusion
• vasectomized partner
• sexual abstinence
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2022-001489-37-NL |
| CCMO | NL81346.056.22 |