Hidradenitis Suppurativa (Acne Inversa)
Conditions
Keywords
Hidradenitis Suppurativa
Brief summary
This is a randomized, double blind, multicenter study in patients with moderate to severe chronic hidradenitis suppurativa in parallel groups, to determine the efficacy and safety of multiple doses of CJM112 in comparison to placebo. The study has two periods to explore preliminary dose effects.
Interventions
BIOLOGICALCJM112
CJM112 Fully human IgG1 monoclonal antibody
DRUGPlacebo
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Male and female patients 18 to 65 years of age with clinically diagnosed chronic HS for at least 1 year (prior to screening) who have undergone previous antibiotic therapy 2. Weight between 50 kg and 150 kg 3. HS-PGA score of at least moderate severity at the time of inclusion with at least 4 abscesses and/or nodules. HS lesions must be present in at least two distinct anatomical areas, and at least one area must be minimally Hurley Stage II (moderate)
Exclusion criteria
1. Use of previous biologics or other specified concomitant medications 2. Use of any systemic treatment for HS in the last 4 weeks prior to randomization 3. Presence of more than 25 draining fistulae. 4. Surgical treatment for HS in the last 4 weeks prior to randomization/first treatment. 5. Women of child-bearing potential and sexually active males unwilling to use a condom during intercourse while taking drug and for 15 weeks after stopping investigational medication. 6. Evidence of active tuberculosis at screening 7. History of severe systemic Candida infections or evidence of Candidiasis in the last two weeks 8. Active systemic or skin infections (other than common cold or HS related) during the two weeks before randomization/first treatment 9. Any live vaccines (including nasal spray flu vaccine) starting from 6 weeks before randomization. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Responder Rate at Period 1: Week 16 | Week 16 | Proportion of study participants achieving a clinical response in Hidradenitis Suppurativa - Physician Global Assessment (HS-PGA) score An HS-PGA responder in period 1 was a participant who had an initial HS-PGA score of at least 3 at baseline (Day 1, inclusion criterion) that decreased by at least 2 points. The six-point Physician Global Assessment (PGA) (scores range from 0-5) based on the number of HS lesions ranges from clear to very severe. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Responder Rate Period 1 at Week 2, 4, 8 and 12 | Week 2, 4, 8 and 12 | Proportion of study participants achieving a clinical response in Hidradenitis Suppurativa - Physician Global Assessment (HS-PGA) score A HS-PGA responder in Period 1 is a study participant who had an initial HS-PGA score of at least 3 at Baseline (Day 1, inclusion criterion) that decreased by at least 2 points. The six-point Physician Global Assessment (PGA) (scores range from 0-5) based on the number of HS lesions ranges from clear to very severe. |
| Pharmacokinetics (PK): Ctrough for CJM112 Period 1 and Period 2 | Week 16 and Week 44 | Ctrough is the serum concentration that is just prior to the beginning of, or at the end, of a dosing interval (mass/volume) for Period 1 (week 16) and Period 2/End of Study (week 44) |
| Pharmacokinetic Profile: T1/2 The Terminal Elimination Half-life for Period 1 & Period 2/End of Study | Week 16 (period 1), Week 44 (End of Study Period 2) | T1/2 The terminal elimination half-life for Period 1 (Week 16) and Period 2/End of Study (Week 44) |
| Immunogenicity - Incidence of ADA-positive and ADA-negative in Participants With or Without Pre-existing Antibodies in Period 1 and Period 2/End of Study | Week 16 (period 1), Week 44 (End of Study Period 2) | Immunogenicity - Incidence of semi-quantitative determination of anti-CJM112 antibodies or ADAs. ADA-positive and ADA-negative in participants with or without pre-existing antibodies Period 1 (week 16) and Period 2/End of Study (week 44) |
| Total Interleukin-17A (IL-17A Homodimer) in Serum at Pre-dose and Post-dose for Period 1 & Period 2 | Pre-dose (Period 1 Day 1 & Period 2 Day 113), Post-dose Period 1(Day 99) and post-dose Period 2 (Day 211) | Total Interleukin-17A (IL-17A homodimer) in serum at Pre-dose Period 1 (Day 1) & Pre-dose Period 2 (Day 113) and Post-dose Period 1 (Day 99) and Post-dose Period 2 (Day 211) |
Countries
Denmark, Germany, Netherlands, Switzerland, United States
Participant flow
Recruitment details
Study with 4 wks screening,two sequential treatment periods 16 wks (Period 1 & Extension Period 2)& 12 wks Follow-up. Randomization 2:1:1 to three sequences:Seq. 1: Period 1: CJM112 High Dose sc then Period 2: placebo sc; Seq. 2: Period 1: Placebo sc then Period 2: CJM112 Low Dose sc; Seq, 3: Period 1: Placebo sc then Period 2: CJM112 High Dose sc
Pre-assignment details
A total of 66 patients were enrolled, randomized and entered into two sequential periods (Period 1 and Extension Period 2) of which 60 patients completed Week 16 in Period 1 and entered Extension Period 2.
Participants by arm
| Arm | Count |
|---|---|
| Period 1: CJM112 High Dose Period 1: CJM112 300mg subcutaneously (s.c.) weekly for 5 doses followed by bi-weekly for 5 doses for a total of 10 doses | 33 |
| Period 1: Placebo Period 1: Placebo subcutaneously (s.c.) weekly for 5 doses followed by bi-weekly for 5 doses for a total of 10 doses | 33 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Period 1 | Adverse Event | 1 | 0 | 0 | 0 | 0 |
| Period 1 | Lost to Follow-up | 3 | 1 | 0 | 0 | 0 |
| Period 1 | Patient/guardian decision | 0 | 1 | 0 | 0 | 0 |
| Period 2 | Adverse Event | 0 | 0 | 4 | 0 | 0 |
| Period 2 | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 |
| Period 2 | Patient/guardian decision | 0 | 0 | 3 | 2 | 1 |
Baseline characteristics
| Characteristic | Period 1: CJM112 High Dose | Period 1: Placebo | Total |
|---|---|---|---|
| Age, Continuous | 36 years STANDARD_DEVIATION 9.8 | 39 years STANDARD_DEVIATION 10.9 | 37 years STANDARD_DEVIATION 10.5 |
| Sex: Female, Male Female | 22 Participants | 22 Participants | 44 Participants |
| Sex: Female, Male Male | 11 Participants | 11 Participants | 22 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 25 / 33 | 23 / 33 | 20 / 29 | 13 / 16 | 14 / 15 |
| serious Total, serious adverse events | 0 / 33 | 1 / 33 | 1 / 29 | 0 / 16 | 0 / 15 |
Outcome results
Primary
Clinical Responder Rate at Period 1: Week 16
Proportion of study participants achieving a clinical response in Hidradenitis Suppurativa - Physician Global Assessment (HS-PGA) score An HS-PGA responder in period 1 was a participant who had an initial HS-PGA score of at least 3 at baseline (Day 1, inclusion criterion) that decreased by at least 2 points. The six-point Physician Global Assessment (PGA) (scores range from 0-5) based on the number of HS lesions ranges from clear to very severe.
Time frame: Week 16
Population: PD analysis set 1 includes all patients who were CJM112-treated or placebo-treated in Period 1 with available PD data and no protocol deviations with relevant impact on PD data in Period 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period 1: CJM112 High Dose | Clinical Responder Rate at Period 1: Week 16 | 10 participants |
| Period 1: Placebo | Clinical Responder Rate at Period 1: Week 16 | 4 participants |
Secondary
Clinical Responder Rate Period 1 at Week 2, 4, 8 and 12
Proportion of study participants achieving a clinical response in Hidradenitis Suppurativa - Physician Global Assessment (HS-PGA) score A HS-PGA responder in Period 1 is a study participant who had an initial HS-PGA score of at least 3 at Baseline (Day 1, inclusion criterion) that decreased by at least 2 points. The six-point Physician Global Assessment (PGA) (scores range from 0-5) based on the number of HS lesions ranges from clear to very severe.
Time frame: Week 2, 4, 8 and 12
Population: PD analysis set 1 includes all patients who were CJM112-treated or placebo-treated in Period 1 with available PD data and no protocol deviations with relevant impact on PD data in Period 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Period 1: CJM112 High Dose | Clinical Responder Rate Period 1 at Week 2, 4, 8 and 12 | Week 2 | 4 count of participants |
| Period 1: CJM112 High Dose | Clinical Responder Rate Period 1 at Week 2, 4, 8 and 12 | Week 4 | 6 count of participants |
| Period 1: CJM112 High Dose | Clinical Responder Rate Period 1 at Week 2, 4, 8 and 12 | Week 8 | 5 count of participants |
| Period 1: CJM112 High Dose | Clinical Responder Rate Period 1 at Week 2, 4, 8 and 12 | Week 12 | 7 count of participants |
| Period 1: Placebo | Clinical Responder Rate Period 1 at Week 2, 4, 8 and 12 | Week 12 | 4 count of participants |
| Period 1: Placebo | Clinical Responder Rate Period 1 at Week 2, 4, 8 and 12 | Week 2 | 3 count of participants |
| Period 1: Placebo | Clinical Responder Rate Period 1 at Week 2, 4, 8 and 12 | Week 8 | 6 count of participants |
| Period 1: Placebo | Clinical Responder Rate Period 1 at Week 2, 4, 8 and 12 | Week 4 | 3 count of participants |
Secondary
Immunogenicity - Incidence of ADA-positive and ADA-negative in Participants With or Without Pre-existing Antibodies in Period 1 and Period 2/End of Study
Immunogenicity - Incidence of semi-quantitative determination of anti-CJM112 antibodies or ADAs. ADA-positive and ADA-negative in participants with or without pre-existing antibodies Period 1 (week 16) and Period 2/End of Study (week 44)
Time frame: Week 16 (period 1), Week 44 (End of Study Period 2)
Population: PK analysis set 1 includes all patients who were CJM112-treated in Period 1 with available PK data \& no protocol deviations with relevant impact on PK data. PK analysis set 2 \& 3 includes all patients from safety analysis set 2 \& set 3 with available PK data \& no protocol deviations with relevant impact on PK data for Period 2/End of Study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Period 1: CJM112 High Dose | Immunogenicity - Incidence of ADA-positive and ADA-negative in Participants With or Without Pre-existing Antibodies in Period 1 and Period 2/End of Study | Pre-existing Antibodies ADA negative | 2 participants |
| Period 1: CJM112 High Dose | Immunogenicity - Incidence of ADA-positive and ADA-negative in Participants With or Without Pre-existing Antibodies in Period 1 and Period 2/End of Study | Pre-existing Antibodies ADA positive | 1 participants |
| Period 1: CJM112 High Dose | Immunogenicity - Incidence of ADA-positive and ADA-negative in Participants With or Without Pre-existing Antibodies in Period 1 and Period 2/End of Study | NO Pre-existing Antibodies ADA negative | 21 participants |
| Period 1: CJM112 High Dose | Immunogenicity - Incidence of ADA-positive and ADA-negative in Participants With or Without Pre-existing Antibodies in Period 1 and Period 2/End of Study | NO Pre-existing Antibodies ADA positive | 9 participants |
| Period 1: Placebo | Immunogenicity - Incidence of ADA-positive and ADA-negative in Participants With or Without Pre-existing Antibodies in Period 1 and Period 2/End of Study | NO Pre-existing Antibodies ADA positive | 4 participants |
| Period 1: Placebo | Immunogenicity - Incidence of ADA-positive and ADA-negative in Participants With or Without Pre-existing Antibodies in Period 1 and Period 2/End of Study | Pre-existing Antibodies ADA negative | 1 participants |
| Period 1: Placebo | Immunogenicity - Incidence of ADA-positive and ADA-negative in Participants With or Without Pre-existing Antibodies in Period 1 and Period 2/End of Study | NO Pre-existing Antibodies ADA negative | 10 participants |
| Period 1: Placebo | Immunogenicity - Incidence of ADA-positive and ADA-negative in Participants With or Without Pre-existing Antibodies in Period 1 and Period 2/End of Study | Pre-existing Antibodies ADA positive | 1 participants |
| Extension Period 2: Placebo/CJM112 High Dose | Immunogenicity - Incidence of ADA-positive and ADA-negative in Participants With or Without Pre-existing Antibodies in Period 1 and Period 2/End of Study | NO Pre-existing Antibodies ADA positive | 1 participants |
| Extension Period 2: Placebo/CJM112 High Dose | Immunogenicity - Incidence of ADA-positive and ADA-negative in Participants With or Without Pre-existing Antibodies in Period 1 and Period 2/End of Study | Pre-existing Antibodies ADA positive | 0 participants |
| Extension Period 2: Placebo/CJM112 High Dose | Immunogenicity - Incidence of ADA-positive and ADA-negative in Participants With or Without Pre-existing Antibodies in Period 1 and Period 2/End of Study | NO Pre-existing Antibodies ADA negative | 9 participants |
| Extension Period 2: Placebo/CJM112 High Dose | Immunogenicity - Incidence of ADA-positive and ADA-negative in Participants With or Without Pre-existing Antibodies in Period 1 and Period 2/End of Study | Pre-existing Antibodies ADA negative | 7 participants |
Secondary
Pharmacokinetic Profile: T1/2 The Terminal Elimination Half-life for Period 1 & Period 2/End of Study
T1/2 The terminal elimination half-life for Period 1 (Week 16) and Period 2/End of Study (Week 44)
Time frame: Week 16 (period 1), Week 44 (End of Study Period 2)
Population: PK analysis set 1 includes all patients who were CJM112-treated in Period 1 with available PK data \& no protocol deviations with relevant impact on PK data. PK analysis set 2 \& 3 includes all patients from safety analysis set 2 \& set 3 with available PK data \& no protocol deviations with relevant impact on PK data for Period 2/End of Study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Period 1: CJM112 High Dose | Pharmacokinetic Profile: T1/2 The Terminal Elimination Half-life for Period 1 & Period 2/End of Study | 16.09 days | Standard Deviation 3.5 |
| Period 1: Placebo | Pharmacokinetic Profile: T1/2 The Terminal Elimination Half-life for Period 1 & Period 2/End of Study | 22.81 days | Standard Deviation 0 |
| Extension Period 2: Placebo/CJM112 High Dose | Pharmacokinetic Profile: T1/2 The Terminal Elimination Half-life for Period 1 & Period 2/End of Study | 19.85 days | Standard Deviation 3.807 |
Secondary
Pharmacokinetics (PK): Ctrough for CJM112 Period 1 and Period 2
Ctrough is the serum concentration that is just prior to the beginning of, or at the end, of a dosing interval (mass/volume) for Period 1 (week 16) and Period 2/End of Study (week 44)
Time frame: Week 16 and Week 44
Population: PK analysis set 1 includes all patients who were CJM112-treated in Period 1 with available PK data \& no protocol deviations with relevant impact on PK data. PK analysis set 2 \& 3 includes all patients from safety analysis set 2 \& set 3 with available PK data \& no protocol deviations with relevant impact on PK data for Period 2/End of Study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Period 1: CJM112 High Dose | Pharmacokinetics (PK): Ctrough for CJM112 Period 1 and Period 2 | 21.4 ug/mL | Standard Deviation 11.6 |
| Period 1: Placebo | Pharmacokinetics (PK): Ctrough for CJM112 Period 1 and Period 2 | 3.1 ug/mL | Standard Deviation 2.6 |
| Extension Period 2: Placebo/CJM112 High Dose | Pharmacokinetics (PK): Ctrough for CJM112 Period 1 and Period 2 | 24.4 ug/mL | Standard Deviation 19 |
Secondary
Total Interleukin-17A (IL-17A Homodimer) in Serum at Pre-dose and Post-dose for Period 1 & Period 2
Total Interleukin-17A (IL-17A homodimer) in serum at Pre-dose Period 1 (Day 1) & Pre-dose Period 2 (Day 113) and Post-dose Period 1 (Day 99) and Post-dose Period 2 (Day 211)
Time frame: Pre-dose (Period 1 Day 1 & Period 2 Day 113), Post-dose Period 1(Day 99) and post-dose Period 2 (Day 211)
Population: PK analysis set 1 includes all patients who were CJM112-treated in Period 1 with available PK data \& no protocol deviations with relevant impact on PK data. PK analysis set 2 \& 3 includes all patients from safety analysis set 2 \& set 3 with available PK data \& no protocol deviations with relevant impact on PK data for Period 2/End of Study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: CJM112 High Dose | Total Interleukin-17A (IL-17A Homodimer) in Serum at Pre-dose and Post-dose for Period 1 & Period 2 | Pre-dose | 361 pg/mL | Standard Deviation 2010 |
| Period 1: CJM112 High Dose | Total Interleukin-17A (IL-17A Homodimer) in Serum at Pre-dose and Post-dose for Period 1 & Period 2 | Post-dose | 1160 pg/mL | Standard Deviation 3190 |
| Period 1: Placebo | Total Interleukin-17A (IL-17A Homodimer) in Serum at Pre-dose and Post-dose for Period 1 & Period 2 | Pre-dose | 163 pg/mL | Standard Deviation 647 |
| Period 1: Placebo | Total Interleukin-17A (IL-17A Homodimer) in Serum at Pre-dose and Post-dose for Period 1 & Period 2 | Post-dose | 943 pg/mL | Standard Deviation 583 |
| Extension Period 2: Placebo/CJM112 High Dose | Total Interleukin-17A (IL-17A Homodimer) in Serum at Pre-dose and Post-dose for Period 1 & Period 2 | Pre-dose | 158 pg/mL | Standard Deviation 372 |
| Extension Period 2: Placebo/CJM112 High Dose | Total Interleukin-17A (IL-17A Homodimer) in Serum at Pre-dose and Post-dose for Period 1 & Period 2 | Post-dose | 821 pg/mL | Standard Deviation 538 |