Hidradenitis Suppurativa
Conditions
Brief summary
This was a Phase 2 study in adult participants with moderate to severe hidradenitis suppurativa (HS). The purpose of the study was to evaluate the efficacy and safety of SAR442970 compared to placebo.
Detailed description
The study duration was up to 40 weeks.
Interventions
DRUGSAR442970
1 mL extractable volume of 150 mg/mL SAR442970 filled in 2 mL glass vial
DRUGPlacebo
1 mL extractable volume of placebo filled in 2 mL glass vial
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Participants with a history of signs and symptoms consistent with hidradenitis suppurativa (HS) for at least 1 year prior to Baseline. * Participants had to have HS lesions present in at least 2 distinct anatomic areas (eg, left and right axilla; or left axilla and left inguinocrural fold), one of which had to be Hurley Stage II or Hurley Stage III. * Participant had to have had an inadequate response to a trial of an oral antibiotic for treatment of HS, exhibited recurrence after discontinuation of antibiotics, demonstrated intolerance to antibiotics, or had a contraindication to oral antibiotics for treatment of their HS as assessed by the Investigator through participant interview and review of medical history. * Participants had to be either biologic and small molecule immunosuppressive-naïve or TNF-experienced. * Participant had to have a total abscess and inflammatory nodule (AN) count of ≥3 at the Baseline visit. * Participant had to have a draining tunnel count of ≤20 at the Baseline visit. * Participant had to have a C-reactive protein (CRP) \>3 mg/L at the screening visit. * Participant who was a candidate for systemic treatment per Investigator's judgment.
Exclusion criteria
* Any other active skin disease or condition (eg, bacterial, fungal or viral infection) that might have interfered with assessment of HS * History of recurrent or recent serious infection * Known history of or suspected significant current immunosuppression * History of solid organ transplant * History of splenectomy * History of moderate to severe congestive heart failure * Receipt of a live vaccine 12 week prior to Baseline visit or receipt of a killed vaccine 2 weeks prior to Baseline visit * History of demyelinating disease (including myelitis) or neurologic symptoms suggestive of demyelinating disease * Participants with a history of malignancy or lymphoproliferative disease other than adequately treated or nonmetastatic squamous cell carcinoma, or nonmetastatic basal cell carcinoma of the skin that was excised and completely cured * Participants with a diagnosis of inflammatory conditions other than HS * Presence of active suicidal ideation, or positive suicide behavior or participant had a lifetime history of suicide attempt, or participant had had suicidal ideation in the past 6 months as indicated by a positive response using the screening or Baseline version of the Columbia-Suicide Severity Rating Scale (C-SSRS) or as assessed by the Investigator through participant interview and review of medical history * A history of an adverse event (AE) to anti-TNF therapy (examples included, but were not limited, to serum sickness or anaphylaxis) for an HS or non-HS indication that would contraindicate readministration of an anti-TNF class therapy * Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicated participation in the study * Female participants who were breastfeeding or considering becoming pregnant during the study * History (within last 2 years prior to Baseline) of prescription drug or substance abuse, including alcohol, considered significant by the Investigator * Laboratory
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Period A (DB Period): Percentage of Biologic and Small Molecule Immunosuppressive-Naïve Participants Who Achieved Hidradenitis Suppurativa Clinical Response (HiSCR50) at Week 16 | Week 16 | The HiSCR50 was used for assessing HS treatment effectiveness in controlling inflammatory manifestations in the population. HiSCR50 was defined as \>=50% reduction from baseline in the total abscess and inflammatory nodule (AN) count, with no increase from baseline in abscess or draining tunnel count. Baseline was defined as the last available value before the first dose of DB study drug. Percentages are rounded off to the tenth decimal place. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Period A (DB Period): Time to Onset of Achieving Hidradenitis Suppurativa Clinical Response (HiSCR50) | Up to Week 16 | Time to onset of achieving HiSCR50 during the DB period was defined as the time from randomization to the first time of achieving HiSCR50 by Week 16. HiSCR50 was defined as \>=50% reduction from baseline in the total AN count, with no increase from baseline in abscess or draining tunnel count. Baseline was defined as the last available value before the first dose of DB study drug. |
| Period A (DB Period): Percentage of Participants Who Achieved Hidradenitis Suppurativa Clinical Response (HiSCR75) at Week 16 | Week 16 | The HiSCR75 was used for assessing HS treatment effectiveness in controlling inflammatory manifestations in the population. HiSCR75 was defined as \>=75% reduction from baseline in the total AN count, with no increase from baseline in abscess or draining tunnel count. Baseline was defined as the last available value before the first dose of DB study drug. |
| Period A (DB Period): Percentage of Participants Who Achieved Hidradenitis Suppurativa Clinical Response (HiSCR90) at Week 16 | Week 16 | The HiSCR90 was used for assessing HS treatment effectiveness in controlling inflammatory manifestations in the population. HiSCR90 was defined as \>=90% reduction from baseline in the total AN count, with no increase from baseline in abscess or draining tunnel count. Baseline was defined as the last available value before the first dose of DB study drug. |
| Period A (DB Period): Percentage of Participants Who Experienced Improvement by at Least 1 International Hidradenitis Suppurativa Severity Score System (IHS4) Stage at Week 16 | Week 16 | The IHS4 was a validated tool to assess HS severity. The determination of IHS4 required counting inflammatory nodules, abscesses and draining tunnels and multiplying each by a specific coefficient. IHS4 score was calculated as: (number of inflammatory nodules multiplied by 1) + (number of abscesses multiplied by 2) + (number of draining tunnels multiplied by 4). A categorial IHS4 score was derived from this weighted score with total score range: mild: (\<=3), moderate: (4 to 10) and severe: (\>=11); higher scores indicated worse outcomes. Improvement in IHS4 by \>=1 IHS4 stage was considered clinically meaningful. |
| Period A (DB Period): Change From Baseline at Week 16 in Absolute Score in International Hidradenitis Suppurativa Severity Score System (IHS4) | Baseline (Day 1) and Week 16 | The IHS4 was a validated tool to assess HS severity. The determination of IHS4 required counting inflammatory nodules, abscesses and draining tunnels and multiplying each by a specific coefficient. IHS4 score was calculated as: (number of inflammatory nodules multiplied by 1) + (number of abscesses multiplied by 2) + (number of draining tunnels multiplied by 4). A categorial IHS4 score was derived from this weighted score with total score range: mild: (\<=3), moderate: (4 to 10) and severe: (\>=11); higher scores indicated worse outcomes. Baseline was defined as the last available value before the first dose of DB study drug. |
| Period A (DB Period): Percentage of Participants Who Experienced a Flare Relative to Baseline at Week 16 | Baseline (Day 1) and Week 16 | HS flare was defined as \>=25% increase in AN count with a \>=2 increase from baseline by Week 16. Baseline was defined as the last available value before the first dose of DB study drug. |
| Period A (DB Period): Percentage of Participants Who Achieved International Hidradenitis Suppurativa Severity Score System (IHS4)-55 at Week 16 | Week 16 | The IHS4 was a validated tool to assess HS severity. The determination of IHS4 required counting inflammatory nodules, abscesses and draining tunnels and multiplying each by a specific coefficient. IHS4 score was calculated as: (number of inflammatory nodules multiplied by 1) + (number of abscesses multiplied by 2) + (number of draining tunnels multiplied by 4). A categorial IHS4 score was derived from this weighted score with total score range: mild: (\<=3), moderate: (4 to 10) and severe: (\>=11); higher scores indicated worse outcomes. IHS4-55 was defined as a 55% reduction in IHS4 score from baseline. Baseline was defined as the last available value before the first dose of DB study drug. |
| Period A (DB Period) + Period B (OLE Period): Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment-Emergent Adverse Events of Special Interest (TEAESIs) | Period A was assessed from first dose of study drug (Day 1 in Period A) up to last dose of study drug + 75 days, up to 192 days; Period B was assessed from first dose in Period B to last dose of study drug + 75 days, up to 168 days | An AE as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE was defined as any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were AEs that developed, worsened or became serious during the TE period. An AESI was an AE (serious or non-serious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required. |
| Period A (DB Period): Percentage of Participants Who Achieved at Least 30% Reduction and at Least 1 Unit Reduction From Baseline in Weekly Average of Daily Hidradenitis Suppurativa Skin Pain Numeric Rating Scale (HS-Skin Pain NRS) at Week 16 | Baseline (Day 1) and Week 16 | The HS-Skin Pain NRS was a unidimensional numeric rating scale (NRS) that allowed for rapid measure of skin pain that was administered multiple times with minimal administrative burden. The HS-Skin Pain NRS had a 24-hour recall period and was completed as a daily diary, ideally at the same time each day (evening) throughout the treatment period. Participants were asked to complete the HS-Skin Pain NRS for 7 consecutive days leading up to the baseline visit with a minimum of 4 completions in their daily diary. The HS-Skin Pain NRS was scored on a 0 to 10 scale; 0: no skin pain and 10: worst skin pain possible. Higher scores indicated worse outcomes. Baseline was defined as the last available value before the first dose of DB study drug. |
| Period A (DB Period) + Period B (OLE Period): Serum SAR442970 Concentrations | Baseline (Day 1), Weeks 4, 8, 10, 12 and 16 (Period A); Weeks 18, 20 and 28 (Period B) | Blood samples were collected at specified timepoints for assessment of serum SAR442970 concentrations. |
| Period B (OLE Period) + Period A+B (DB+OLE Period): Number of Participants With Anti-SAR442970 Antibody Response | Period B: Placebo-SAR442970 arm were assessed from first dose of study drug in Period B up to approximately 20 weeks. Period A+B: SAR442970-SAR442970 arm were assessed from first dose of study drug in Period A up to 36 weeks | Serum samples were collected at specified timepoints for assessment of anti-SAR442970 antibody response. Treatment-emergent anti-drug antibody (ADA) were defined as participants with at least 1 treatment-induced/boosted ADA at any time after first study drug administration up to the last available ADA sample collection. Number of participants with treatment-emergent ADA response are presented. |
Countries
Australia, Belgium, Canada, Chile, Czechia, Denmark, France, Germany, Greece, Italy, Netherlands, Poland, Spain, Sweden, United States
Contacts
STUDY_DIRECTORClinical Sciences & Operations
Sanofi
Participant flow
Recruitment details
The study started to screen participants in June 2023 and concluded enrollment in April 2024.
Pre-assignment details
A total of 86 participants were randomized in a 2:1 ratio to receive either SAR442970 150 milligrams (mg) or a matching placebo. The study consisted of a screening period (up to 4 weeks), a treatment period (16-week Period A \[double blind {DB}\] and 12-week Period B \[open-label extension {OLE}\]), and safety follow-up period (8 weeks).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 37.0 years STANDARD_DEVIATION 13.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 66 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 58 | 0 / 26 | 0 / 51 |
| other Total, other adverse events | 11 / 28 | 32 / 58 | 6 / 26 | 16 / 51 |
| serious Total, serious adverse events | 0 / 28 | 0 / 58 | 0 / 26 | 0 / 51 |
Outcome results
None listed