A Phase III Study to Investigate Efficacy, Safety and Tolerability of Iptacopan Compared With Placebo in Participants Aged 18 to 85 Years With gMG.
Purpose
The study is a randomized, double-blind, placebo-controlled, multicenter, Phase III study, to evaluate efficacy, safety and tolerability of iptacopan in patients with AChR+ gMG who are on stable SOC treatment. Participants who meet the eligibility criteria will be randomized in a ratio of 1:1, to receive either iptacopan or matching placebo, for 6 months (180 days) while continuing on a stable SOC treatment. The randomization will be stratified based on region.
Condition
- Generalized Myasthenia Gravis
Eligibility
- Eligible Ages
- Between 18 Years and 85 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Adult patients with generalized Myasthenia Gravis (age 18-85 years) at screening - Positive serology testing for AChR+ antibody at screening - Myasthenia Gravis Foundation of America (MGFA) Class II-IV gMG at screening and likely not in need of a respirator for the duration of the study, as judged by the Investigator. - The confirmation of the diagnosis of gMG should be documented and supported by ≥1 of the following 3 tests: - History of abnormal neuromuscular transmission demonstrated by single-fiber electromyography or repetitive nerve stimulation. - History of positive test with short-acting acetylcholinesterase inhibitors (e.g. neostigmine or edrophonium chloride) - Patient has demonstrated improvement in MG signs on oral acetylcholinesterase inhibitors as assessed by the treating physician. - Baseline MG-ADL score ≥6, with ≥50% of the total score due to non-ocular symptoms - Participants receiving at least one of the following treatments for gMG for ≥ 6 months prior to baseline; - One or more NSISTs or - plasmapheresis, plasma exchange, or intravenous immunoglobulin (at least quarterly) to control symptoms despite treatment with steroids and NSISTs; or - an approved FcRN antagonist approved for gMG; or - rituximab or - other approved gMG disease modifying therapies excluding complement inhibitors. - Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection is required prior to the start of study treatment. If the participant has not been previously vaccinated, or if a booster was required, the vaccine should be given according to local guidelines at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post-vaccination, prophylactic antibiotic treatment should be initiated at the start of study treatment and continued until at least 2 weeks after vaccination or booster was completed. Note: For US sites participating in Study CLNP023Q12301, the completion of the meningococcal vaccination or booster is required for patients with gMG prior to initiating study treatment, irrespective of prophylactic antibiotic use.
Exclusion Criteria
- Have been treated with intravenous immunoglobulin (IVIG)/plasma exchange (PLEX) in the past month, with rituximab in the past 6 months, eculizumab in the past 2 months, ravulizumab or other complement inhibitors in the past 3 months, efgartigimod or other anti- FcRn therapies in the past 3 months, or had a thymectomy in the past 6 months or a planned thymectomy during the trial period. - Participants with clinically significant active or chronic uncontrolled bacterial, viral, or fungal infection at screening, including patients who test positive for an active viral infection at screening with: Active Hepatitis B Virus (HBV); Active Hepatitis C Virus (HCV); - Human Immunodeficiency Virus (HIV) positive serology associated with an Acquired Immune Deficiency Syndrome (AIDS)-defining condition or with a cluster of differentiation 4 (CD4) count - 200 cells/mm3 - Female participants who are pregnant or lactating, or are intending to become pregnant. - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant from menarche until becoming post-menopausal, unless they are using effective methods of contraception during dosing of study treatment and an additional one week following cessation of study treatment. Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., hormonal profile confirming menopause and/or age-appropriate history of vasomotor symptoms). - Active systemic bacterial, viral (including COVID-19) or fungal infection or any major episode of infection that required hospitalization or injectable antimicrobial therapy within 14 days prior to study drug administration. - History of recurrent invasive infections caused by encapsulated organisms, e.g., N. meningitidis and S. pneumoniae. - Presence of fever ≥ 38 °C (100.4 °F) within 7 days prior to study drug administration
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- The study is a randomized, double-blind, placebo-controlled, multicenter, Phase III study, to evaluate efficacy, safety and tolerability of iptacopan in patients with AChR+ gMG who are on stable SOC treatment. Participants who meet the eligibility criteria will be randomized in a ratio of 1:1, to receive either iptacopan or matching placebo, for 6 months (180 days) while continuing on a stable SOC treatment. The randomization will be stratified based on region.
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Masking Description
- This is a participant, investigator, and sponsor-blinded study. Participants, investigator staff, persons performing the assessments and the Clinical Trial Team will remain blinded to the identity of treatment from the time of randomization until database lock after all participants have completed the double-blind treatment period. The following methods will be used to ensure that blinding is properly maintained: 1. Randomization data are kept strictly confidential until the time of unblinding and will not be accessible by anyone involved in the study 2. The identity of the treatment will be concealed by the use of study treatments that are all identical in packaging, labeling, schedule of administration, appearance, taste, and odor
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Iptacopan |
Iptacopan orally for 6 months (double-blind) followed by open-label iptacopan for up to 60 months |
|
|
Placebo Comparator Matching Placebo |
Placebo orally for 6 months (double-blind) followed by open-label iptacopan for up to 60 months |
|
Recruiting Locations
Vanderbilt University Medical CenterX
Nashville 4644585, Tennessee 4662168 37221
Nashville 4644585, Tennessee 4662168 37221
More Details
- Status
- Recruiting
- Sponsor
- Novartis Pharmaceuticals
Detailed Description
The study consists of a 6-month double-blind treatment period for the primary efficacy and safety analysis followed by a maximum duration of 60 month open label extension period. A safety follow up assessment will be performed, one 7 days after the last administration of study treatment and one 30 days after the last administration of study treatment for all participants.