The following changes were subject to this amendment: - Storage conditions of the placebo in Table 3 were clarified. - The timing for contacting the medical monitor for unblinding a participant’s treatment assignment was clarified. - Procedures for rescreening were clarified. - An additional description of monitoring was provided. - It was clarified that concomitant medications should have been used in alignment with the approved label in the respective country and per doses outlined in the protocol. - It was specified that approximately 30% of enrolled participants were allowed to be on stable doses of oral antibiotics for at least 4 weeks prior to baseline. - It was specified that investigators should have considered the effects on the metabolism of cytochrome P450 substrates with narrow therapeutic indices when the study drug was initiated or discontinued. - The process for missed or delayed doses was clarified. - It was clarified that the investigator should have determined whether another rescue medication would have been more appropriate for a participant who was previously intolerant or had a contraindication to both minocycline and doxycycline. - The reasons for discontinuation of the study drug were updated. - It was specified that instructions for collecting and handling biological samples were provided in the laboratory manual. - Procedures for the collection of samples for exploratory biomarker analysis (US only) were added. - The sample storage and shipping flow for ADA samples was added. - Duplicate sections describing the data monitoring committee structure were removed. - The schedule of assessments for HIV testing, ECG assessments, vital signs, fasting lipid levels, and evaluation for symptoms of clinical depression was modified. - The list of AEs of special interest was expanded. - For the primary endpoint, the reduction was changed from 30% to 50%. - Information on handling data security breaches was provided.

The following changes were subject to this amendment: - Measures were added to ensure the protection of personal data and ensure confidentiality. - Text was added to further define source documents. - Requirements for participant competency with dosing at home were clarified. - The SAE process and the location for recording AE/SAE information were clarified. - Procedures for the assessment and follow-up for liver safety were updated. - The regions to be assessed for the degree of erythema were updated. - It was clarified that the PGIC assessment at week 16 asked the participant about pain since treatment began in the study. - The version and date were added to the header and title page.

The following changes were subject to this amendment: - "Pivotal" was added to the study protocol title. - The term “study intervention” was changed to “study drug” when referring to the investigational product. - The rationale and background information were updated to specify indications that were currently being studied. - The observation period was modified to include weeks 16 and 17 for QW and weeks 16 and 18 for Q2W. - The number of days pain diaries needed to be completed for a participant to be randomized was clarified. - It was clarified that after a delayed or missed dose, participants should have returned to the original visit and dosing schedule. - For trough concentrations, “serum” was replaced with “plasma.” - The secondary pain endpoint was moved to be the last secondary endpoint. - The Patient Global Assessment of Skin Pain endpoint was changed from a 30% reduction to a 3-point reduction. - The disease flare endpoint was modified to be through 16 weeks of treatment. - The description of DMC membership was clarified. - The rationale for the placebo-controlled period was added. - Inclusion criterion 5 was revised from a total abscess and inflammatory nodule count of ≥3 to ≥5. - Legally authorized representatives were removed as being able to sign the informed consent. - Exclusion criterion 4 was revised to only exclude inflammatory bowel disease. - Exclusion criterion 6 was revised to clarify moderate to severe for both renal disease and liver disease. - Exclusion criterion 11 was removed as it duplicated Exclusion criterion 9. - Exclusion criterion 12 was reworded to clarify that it was not a separate criterion. - Exclusion criterion 22 was revised for clarity and to exclude laser or intense light therapy in anatomic areas of HS lesions. - The definition of renal impairment in Exclusion criterion 31 was modified. - Lifestyle considerations regarding alcohol consumption were added.

The following changes were subject to this amendment: - The legal registered address for the sponsor was updated. - The sponsor signatory was updated. - The overall approximate number of participants to be enrolled for the study overall and in Part B, along with the approximate study power, was updated. - The timepoint for the primary objective and endpoint in Part A was updated. - The primary objective and endpoint in Part B were changed from HiSCR to HiSCR75. - The percentages of participants who achieved HiSCR90/100/50 at Week 16 were added as secondary objectives and endpoints in Part B. - The HiSCR percentage definition was revised. - The percentages of participants who achieved HiSCR75/90/100/50 at Weeks 2, 4, 8, 12, and 32 were added to exploratory objectives and endpoints in Part B. - The NRS Patient Global Assessment Skin Pain was added as a screening assessment. - It was clarified that participants randomized to Q2W arms did not need to complete the Week 17 visit. - Grammatical changes were made. - The version and date for the header and title page were revised.