Primary Objective:1. To evaluate the efficacy of sonelokimab at 2 different dose levels (120 mg, 240 mg) compared with placebo in the treatment of participants withactive moderate to severe hidradenitis suppurativa.Secondary Objectives:1. To…
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Percentage of participants achieving Hidradenitis Suppurativa Clinical
Response (HiSCR) 75 at Week 12, where HiSCR75 is defined as at
least a 75% reduction from baseline in abscess and inflammatory nodule (AN)
count, with no increase from baseline in abscess or draining fistula
count.
Secondary outcome
1. Proportion of participants achieving HiSCR50 at Week 12.
2. Change from baseline in International Hidradenitis Suppurativa Severity
Score System (IHS4) at Week 12;
3. Proportion of participants achieving a Dermatology Life Quality Index (DLQI)
total score of <=5 at Week 12.
4. Proportion of participants achieving at least 30% reduction and at least
1-unit reduction from baseline in Numerical Rating Scale (NRS) 30
in Patient's Global Assessment of Skin Pain (PGA) of Skin Pain at Week 12 among
subjects with baseline NRS >=3.
Background summary
Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent
debilitating skin disease that usually presents in early adulthood.
Predisposing risk factors include family history, with ~34% of first-degree
relatives affected, in addition to smoking and obesity. HS manifests as painful
inflammatory skin lesions in the axillary, inguinal, gluteal, and perianal
regions and is characterized by inflammatory nodules and abscesses complicated
by the formation of pusdischarging dermal tunnels, also known as sinus tracts
or fistulas. Dermal tunnels are a unique morphologic feature of HS, recognized
as a source of inflammation and an active mediator of disease pathogenesis.
Clinically, tunnels cause significant pain and morbidity for patients, and are
predictors of poor prognosis and a more aggressive disease course.
Over time, chronic, uncontrolled, and inadequately treated inflammation results
in irreversible tissue destruction and scarring, which is not susceptible to
medical therapy. Severe scarring is associated with further debilitating
complications, including contractures, limitations in limb mobility, and
lymphedema. Once fibrotic architectural changes occur, surgery is the only
recommended therapeutic option to reduce the volume of fibrotic tissue and
symptom burden; however, recurrence rates following surgery are significant.
Therefore, targeting the
inflammatory phase of HS and reducing inflammatory lesion burden should be a
core element of disease management to prevent irreversible tissue destruction
and debilitation.
The high symptom burden of HS (chronic pain, large amounts of purulent
secretions, malodor, and fatigue) has a profound impact on patient quality of
life and contributes to a significant deterioration in physical and mental
health. People with HS suffer from greater pain and associated psychologic
comorbidities, including depression, anxiety, disability, and impairments in
quality of life, compared with those with other dermatologic conditions.
Management of HS requires a multifaceted approach, which may include lifestyle
modifications, pain management, topical therapies (antibiotics, antiseptics,
and intralesional corticosteroids), systemic therapies (antibiotics, retinoids,
and biologics), and invasive surgical treatments (incision and drainage of
active lesions, deroofing procedures, and radical excision) The only approved
biologic treatment option for patients with moderate to severe HS is the
anti-tumor necrosis factor (TNF) inhibitor adalimumab (Humira®).
Sonelokimab
Sonelokimab is a tri-specific nanobody that selectively inhibitsIL-17A and
IL-17F. The central moiety binds to serum albumin to extend the half-life in
vivo. Sonelokimab is expressed in the yeast *Pichia pastoris* and is composed
of 378 amino acids. It is around a quarter of the size of conventional
monoclonal antibodies.
In conjunction with selective inhibition of IL-17A and IL-17F, potential
advantages that can differentiate sonelokimab from conventional monoclonal
antibodies include its smaller size and albumin binding capacity. The smaller
size of the sonelokimab nanobody compared with conventional monoclonal
antibodies may enable differential deep tissue penetration. Furthermore, the
albumin binding domain provides a mechanism for enrichment of sonelokimab at
sites of chronic inflammation associated with edema and accumulation of
albumin-rich fluid. Taken together, these characteristics are predicted to
enable enhanced tissue penetration into HS lesions and impact on disease
mechanisms. Drug tissue penetration is an important consideration in the
treatment of HS, as disease presentation is often characterized by deep dermal
morphologies (e.g. tunnels/fistulas) that are sites of inflammation and
contribute to disease progression.
Study objective
Primary Objective:
1. To evaluate the efficacy of sonelokimab at 2 different dose levels (120 mg,
240 mg) compared with placebo in the treatment of participants with
active moderate to severe hidradenitis suppurativa.
Secondary Objectives:
1. To evaluate the safety and tolerability of sonelokimab at 2 different dose
levels (120 mg, 240 mg) compared with placebo in the treatment of
participants with active moderate to severe hidradenitis suppurativa;
2. To assess the pharmacokinetics (PK) and immunogenicity of sonelokimab at 2
different dose levels (120 mg, 240 mg) in the treatment of
participants with active moderate to severe hidradenitis suppurativa.
Exploratory Objective:
1. The exploratory objective is to assess biomarkers of participants with
active moderate to severe hidradenitis suppurativa.
Study design
The planned study duration for individual participants will be up to 32 weeks,
including a screening period of up
to 4-weeks, 24-week treatment period, and a 4-week Safety Follow-up period.
This is a Phase 2 multi-center randomized, parallel-group, double-blind,
placebo-controlled 2-part study evaluating the efficacy, safety, PK and
immunogenicity of sonelokimab in participants with active moderate to severe
hidradenitis suppurativa (HS). The study includes adalimumab treatment as an
active reference arm; however, no formal comparison of sonelokimab vs
adalimumab is planned.
At the Screening Visit, each participant will provide informed consent, be
assigned a unique participant number via the Interactive Response Technology
(IRT), be assessed for eligibility with the inclusion and exclusion criteria
and perform study activities as described in the protocol. Participants will
undergo screening for up to 4 weeks before randomization to establish
eligibility.
In Part A, eligible participants will be randomized (2:2:2:1) to receive either
sonelokimab 120 mg or sonelokimab 240 mg, or matching placebo, or adalimumab up
to Week 12. Participants randomized to adalimumab will receive 160 mg on Day 1
and 80 mg every 2 weeks up until Week 10. Randomization will be stratified by
Hurley Stage status (II and III) and prior biologic use (yes/no).
The primary efficacy analysis will be performed at Week 12, comparing each of
the sonelokimab treatment groups (sonelokimab 120 mg and sonelokimab 240 mg)
versus placebo.
In Part B, participants who were initially randomized to sonelokimab 120 mg or
240 mg will continue treatment for the remainder of the study. Participants
initially randomized to placebo will be re-randomized (1:1) to either
sonelokimab 120 mg or 240 mg and will receive this treatment for the remainder
of the study. Re-randomization will also be stratified by Baseline Hurley Stage
status (II and III) and prior biologic use (yes/no at Screening).
Participants initially randomized to the adalimumab reference arm will be
reallocated to treatment with sonelokimab 240 mg for the remainder of the study.
After the End of Treatment visit at Week 24, all participants will be followed
for safety for additional 4 weeks, i.e., through Week 28.
Intervention
Test Product, Dose and Mode of Administration:
Sonelokimab will be presented as a prefilled syringe as sterile solution for
subcutaneous (SC) injection.
Depending on the randomized treatment arm, participants in the sonelokimab
treatment arms will receive either:
* Arm 1: sonelokimab 120 mg at Weeks 0, 2, 4, 6, 8, followed by injections
every 4 weeks through Week 20;
at Weeks 10, 14, and 18 participants will receive placebo injections to
maintain the blind;
* Arm 2: sonelokimab 240 mg at Weeks 0, 2, 4, 6, 8, followed by injections
every 4 weeks through Week 20;
at Weeks 10, 14, and 18 participants will receive placebo injections to
maintain the blind.
Depending on the randomized treatment arm, participants in the placebo or
adalimumab arms will receive either:
* Arm 3: sonelokimab-matching placebo will be given as SC injection through
Week 12, with injections at
Week 0, 2, 4, 6, 8, and 10.
o Sonelokimab-matching placebo will be presented as a prefilled syringe as
sterile solution for SC injection.
o At the beginning of Part B at Week 12, participants in the placebo group will
be re-randomized to one of the following 2 groups:
* Sonelokimab 120 mg at Weeks 12, 14, 16, 18, and 20;
* Sonelokimab 240 mg at Weeks 12, 14, 16, 18, and 20.
* Arm 4: adalimumab will be given as 160 mg at Week 0, followed by 80 mg once
every 2 weeks; at Weeks 2, 4, 6, 8, and 10.
o Adalimumab will be presented as a prefilled syringe as sterile solution for
SC injection.
o At the beginning of Part B at Week 12, participants in the adalimumab
reference arm will be reallocated to receive sonelokimab 240 mg treatment for
the remainder of the study at Weeks 12, 14, 16, 18, and 20.
Study burden and risks
Participation in this study may help generate future benefit for larger groups
of patients with HS if sonelokimab proves to be successful in treating this
disease to address an unmet medical need.
Sonelokimab has shown efficacy in 2 clinical studies in patients with
psoriasis: a Phase 1 study (Study M1095-PSO-101) and a Phase 2 study (Study
M1095-PSO-201). However, sonelokimab has not been studied in patients with HS
and no direct benefit can be assumed.
The study has also been designed to minimize potential risks to participants.
All subjects will undergo screening procedures aimed at reducing the likelihood
and impact of any such risks. In addition, regular safety monitoring during the
treatment period for all subjects will ensure that any
unanticipated effects of study participation are identified promptly and
managed appropriately.
Potential Risks of Sonelokimab
In common with other potentially immune modulating agents, sonelokimab may
increase the risk of infections, and adverse events (AEs) of infection have
occurred in prior clinical studies with
sonelokimab. Blockade of the IL-17 pathway using monoclonal antibodies
targeting IL-17A, IL-17A/F, or IL-17RA has been specifically associated with an
increased risk of mucocutaneous
candida infections. Patients with active infection will be excluded from this
study and any infections occurring during the study will be monitored as AEs.
Candida infections will be
considered adverse events of special interest(AESIs).
Injection site reactions are a common finding with subcutaneously administered
biologic therapies and have previously been observed in up to 3% of patients
receiving sonelokimab. Injection site
reactions are readily detectable and usually manageable with standard
treatments. Occurrence of injection site reactions will be monitored as AEs in
this study.
All protein therapeutics have the potential to be immunogenic. Manifestations
of systemic hypersensitivity may include anaphylaxis, pruritus, hypotension,
serum sickness, or cutaneous
reactions. Events of pruritus and dermatitis have been reported in sonelokimab
clinical studies. These events are not correlated with the development of
anti-drug antibodies (ADA) to
sonelokimab. Potential hypersensitivity events will be monitored closely in
this study and guidance on events where study treatment should be discontinued
is given in the protocol.
IL-17 is proposed to play a role in maintaining the physiologic, healthy state
of the intestinal mucosa. Blockade of the IL-17 pathway by mAbs to IL-17A,
IL-17A/F, or the IL-17RA has been
associated with a potentially increased risk of inflammatory bowel disease. In
clinical studies to date, no new cases of inflammatory bowel disease (IBD) have
been associated with sonelokimab.
Events of diarrhea have been reported in Study M1095-PSO-201, at rates similar
to the reference arm (secukinumab, IL-17A inhibiting mAb). Because diarrhea may
occur as an early sign of
disruption of epithelial barrier integrity and intestinal immune homeostasis,
diarrhea will be followed as AESI in this study.
Other safety topics evaluated for sonelokimab, but where a potential risk is
not currently specifically identified are discussed in the sonelokimab
investigator*s brochure (IB).
MoonLake Immunotherapeutics AG Dorfstrasse 29
Zug 6300
CH
MoonLake Immunotherapeutics AG Dorfstrasse 29
Zug 6300
CH
Listed location countries
Age
Inclusion criteria
1. >=18 years of age.
2. Diagnosed with HS and has a history of signs and symptoms of HS dating back
at least 6 months.
3. Total AN count (i.e., abscesses and/or inflammatory nodules) of >=5.
4. Subject has HS lesions present in >=2 distinct anatomical areas at least one
of which must contain single or multiple fistulas (i.e., be Hurley Stage II or
III);
5. Subject had an inadequate response to appropriate systemic antibiotics for
treatment of HS (or demonstrated intolerance to, or had a contraindication to,
systemic antibiotics for treatment of their HS).
6. Participants must a suitable candidate for treatment with adalimumab per
approved local product information. If a chest X-ray or computed tomography
(CT) for tuberculosis (TB) screening is required per local guidance, the X-ray
or CT must have been taken within 3 months prior to the Screening.
7. If the subject is female, must be of non-childbearing potential or if of
childbearing potential, participant must agree to use highly effective methods
of contraception.
8. Women of childbearing potential must have a negative serum human chorionic
gonadotropin (hCG) pregnancy test at screening and a negative urine pregnancy
test at Week 0/Day1 prior to the first administration of study treatment.
9. If male, participant must be willing to use a condom when sexually active
with a partner of childbearing potential during the study and for 12 weeks
after the last dose of study drug, unless surgically sterile.
10. Participant is considered reliable and capable of adhering to the protocol,
visit schedule, or medication intake according to the judgment of the
investigator.
11. Participant is able to understand and provide signed informed consent.
Exclusion criteria
1. Known hypersensitivity to sonelokimab, adalimumab or any of its excipients.
2. Draining fistula count of >=20.
3. Any other active skin disease or condition that may interfere with the
assessment of HS.
4. Subject who currently use or plan used one or more prohibited treatments
specified in this protocol.
5. Subjects enrolling in the non-antibiotic strata: use of systemic antibiotics
for the treatment of HS within 28 days.
6. Previous exposure or subject in a study of brodalumab (anti-IL-17RA) and/or
bimekizumab (anti-IL17 A/F).
7. Unsuitable for interleukin (IL)-17A therapy and anti-tumor necrosis factor
alpha (TNFα) therapy.
8. Prior exposure to more than 2 biologic response modifiers.
9. Diagnosis of ulcerative colitis or Crohn's disease.
10. Subject has an active infection or history of infections.
11. Participant with evidence of tuberculosis infection (TB) at screening
unless the following criteria apply:
i. A full TB work-up within 12 weeks establishes no evidence of active TB
infection.
ii. Positive for latent TB per work-up must have completed sufficient treatment
at least 4 weeks prior.
12. Any current nontuberculous mycobacterial (NTM) infection or any history of
pulmonary NTM infection.
13. Concurrent acute or chronic viral hepatitis B virus (HBV) or hepatitis C
virus (HCV) infection.
14. Evidence of human immunodeficiency virus (HIV) infection.
15. Tests positive for Severe Acute Respiratory Syndrome Coronavirus 2
(SARS-CoV-2) infection.
16. Concurrent malignancy or a history of malignancy during the past 5 years of
with the following exceptions:
a. <=3 successfully excised or ablated, basal cell carcinomas of the skin.
b. One squamous cell carcinoma of the skin not worse than Stage T1 that has
been successfully treated, with no signs of recurrence or metastases for at
least the past 2 years.
c. Actinic keratosis.
d. Squamous cell carcinoma in situ of the skin successfully treated >6 months.
e. Localized carcinoma in situ of the cervix treated and considered cured.
17. History of a lymphoproliferative disorder including lymphoma or current
signs and symptoms suggestive of lymphoproliferative disease.
18. Primary immunodeficiencies, prior splenectomy, or suppressive conditions,
including subjects taking immunosuppressive therapy following organ transplants.
19. Had major surgery (e.g., hip replacement, aneurysm removal) within 6 months
or is planning to have major surgery during the study.
20. History or concurrent clinically significant medical conditions or any
other reason, including any physical, psychological, or psychiatric condition,
that would compromise the safety or interfere with the subject's participation
in the study, would make the participant an unsuitable candidate to receive
study drug, or would put the participant at risk.
21. Has received live (including attenuated) vaccination within 8 weeks or
planned during the study and up to at least 12 weeks after the last dose of
study drug.
22. Has received Bacillus Calmette-Guérin vaccination within 1 year.
23. Presence of active suicidal ideation, or positive suicidal behavior; any
history of suicidal attempt (including an actual attempt, interrupted attempt,
or aborted attempt), or suicidal ideation in the past 6 months.
24. Presence of moderately severe depression or severe depression. Subjects are
permitted to use 1 medication to treat depression provided dose is stable for 4
weeks prior. Subjects on multiple medications for depression are excluded from
the study.
25. Severe cardiovascular comorbidities including history of myocardial
infarction, unstable angina pectoris, stroke or heart failure New York Heart
Association (NYHA) III or IV), or uncontrolled hypertension.
26. Clinically significant ECG abnormalities on centrally read ECG at the
Screening.
27. Subject with laboratory abnormalities at the Screening.
28. Subject is enrolled in another interventional investigational study for a
device or drug or has been so enrolled in the last 28 days prior or within 5
half-lives of the study drug prior to the Screening, whichever is longer.
29. Subject is pregnant or breastfeeding or plans to become pregnant while
enrolled in the study and up to 12 weeks after the last dose of study drug;
30. History of chronic alcohol or drug abuse in the past year.
31. Subject is an employee, or direct relative of an employee, of the sponsor,
at a study site, or of a third-party organization involved in the study.
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 | EUCTR2021-005928-38-NL |
| CCMO | NL80713.100.22 |