|Study title||A Phase 2, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of pegcetacoplan in subjects with Amyotrophic Lateral Sclerosis (ALS)|
|UK Chief Investigator||Ammar Al-Chalabi|
|Research summary||This study will evaluate the efficacy and safety of pegcetacoplan in approximately 228 patients with ALS over 116 weeks. Clinical studies indicate that pegcetacoplan has the potential to delay disease progression by targeting the C3 protein of the complement system, which is a part of the immune system that enhances the ability of the body to get rid of microbes and damaged cells.
After a 6-week screening period, patients will be randomly assigned to receive a bi-weekly dose of 1080 mg of pegcetacoplan or placebo for 52 weeks, after which all patients will receive pegcetacoplan at the same dose for a further 52 weeks. The off-treatment follow-up period is 6 weeks.
Patients will undergo physical examinations, electrocardiograms, blood and urine tests, and will have to complete questionnaires to measure disease progress.
|Inclusion/exclusion criteria||INCLUSION CRITERIA
1. Sporadic ALS diagnosed as definite, probable, or laboratory-supported probable as defined by the revised El Escorial criteria (Brooks et al. 2000).
2. At least 18 years of age.
3. Slow vital capacity ≥ 60% of the predicted value at screening.
4. Onset of ALS symptoms within 72 weeks prior to screening.
5. Total ALSFRS-R score of ≥ 30 at screening.
6. Women of childbearing potential defined as any woman who has experienced menarche and who is NOT permanently sterile or postmenopausal a. must have a negative pregnancy test at screening and b. must agree to use protocol defined methods of contraception for the duration of the study and 90 days after their last dose of investigational product. i. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause.
7. Males must agree to a. use protocol defined methods of contraception and b. refrain from donating sperm for the duration of the study and 90 days after their last dose of investigational product.
8. Have vaccination against Streptococcus pneumoniae, Neisseria meningitidis (types A, C, W, Y, and B), and Haemophilus influenzae (type B) either within 5 years prior to Baseline Visit 2b, or agree to receive vaccination at least 7 days prior to Baseline Visit 2b. Vaccination is mandatory, unless documented evidence exists that subjects are nonresponders to vaccination (as evidenced by titers or display titer levels within acceptable local limits).
9. Willing and able to give informed consent and comply with study procedure and assessments (including at-home assessments).
1. Confirmed or suspected other causes of neuromuscular weakness.
2. Diagnosis of another neurodegenerative disease(s).
3. Subject with significant cognitive impairment, clinical dementia, or psychiatric illness that in the opinion of the investigator may increase subject’s risk by participating in the study or confound the outcome of the study.
4. Subjects with a significant pulmonary disorder not attributed to ALS or who require treatments that might complicate the evaluation of the effect of ALS on respiratory function (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, cystic fibrosis, pulmonary arterial hypertension).
5. Current use or anticipated need, in the opinion of the investigator, of a diaphragm pacing system during the randomized treatment period.
6. Riluzole initiation or change in dose within 30 days prior to the start of the screening period or planned initiation during study participation. If using riluzole, the subject should remain on the drug throughout the duration of study participation, but the dosage may be altered or the drug discontinued by the investigator for any safety concern. Riluzole-naive subjects are allowed in the study.
7. Edaravone initiation or change in dose within 60 days prior to the start of the screening period or planned initiation during study participation. If using edaravone, the subject should remain on the drug throughout the duration of study participation, but the dosage may be altered or the drug discontinued by the investigator for any safety concern. Edaravone-naive subjects are allowed in the study.
8. Positive response to Item 4 or 5 of the Columbia Suicide Severity Rating Scale.
9. Subjects with detectable hepatitis C by polymerase chain reaction at screening.
10. Subjects with chronic inactive hepatitis B with viral loads > 1000 IU/mL (> 5000 copies/mL) at screening. Eligible subjects who are chronic active carriers (≤ 1000 IU/mL) must receive prophylactic antiviral treatment according to local country guidelines (eg, entecavir, tenofovir, lamivudine).
11. History of an aggressive lymphoma or presence of a lymphoma requiring therapy by itself.
12. Active or overt malignant disease other than basal cell carcinoma or cutaneous squamous cell carcinoma.
13. Received organ transplant.
14. Presence or suspicion of liver dysfunction as indicated by elevated alanine aminotransferase, aspartate aminotransferase, or bilirubin levels > 2 × the upper limit of normal.
15. Presence or suspicion of severe recurrent or chronic infections that, in the opinion of the investigator, increase the subject’s risk by participating in the study.
16. Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days or within 5-half lives of the treatment (whichever is longer) prior to the start of the screening period or during study participation.
17. Use of any other complement inhibitor within 30 days or within 5-half lives of the treatment (whichever is longer) prior to the start of the screening period or during study participation.
18. If breastfeeding, unwilling to discontinue for the duration of the study and for at least 90 days after final dose of drug.
19. Inability to cooperate or any condition that, in the opinion of the investigator, could increase the subject’s risk by participating in the study or confound the outcome of the study.
|Current status||Closed to recruitment|
|Locations||King’s College Hospital, London
St George’s Hospital (Tooting), London
Royal Sussex County Hospital & Princess Royal Hospital, Brighton
|Contact details||Tracy Healey
|Recruitment group(s)||Interventional (clinical trial)|
|Recruitment target(s)||15 participants (UK)|
|Key dates||Actual opening date: 05 August 2021
Recruitment planned end date: 01 September 2023
|Funder(s)||Apellis Pharmaceuticals, Inc.|
|Sponsor||Apellis Pharmaceuticals, Inc.|
|Study design||Double-blind, placebo-controlled, randomised controlled trial (RTC)|
|Intervention (if applicable)||Drug: Pegcetacoplan
|Phase (if applicable)||Therapeutic exploratory trial (Phase II)|
|Outcome measures||Clinical trial of an investigational medicinal product|
|Publications / Results reports||Links will be provided when papers are published.|
|Participant Information Sheet|