A Study to Evaluate the Safety and Efficacy of Pegcetacoplan in Subjects with ALS

• Register: EUCTR
• Last refreshed on: 18 July 2023
• Main ID: EUCTR2019-003797-10-IE
• Date of registration: 03/09/2020
• Prospective Registration: Yes
• Primary sponsor: Apellis Pharmaceuticals, Inc.
• Public title: A Study to Evaluate the Safety and Efficacy of Pegcetacoplan in Subjects with ALS
• Scientific 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)
• Date of first enrolment: 06/04/2021
• Target sample size: 228
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-003797-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: double-blind, placebo-controlled period followed by open-label (pegcetacoplan) treatment If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, Czech Republic, Czechia, France, Germany, Ireland, Italy, Japan, Netherlands, Poland, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical trial
• Affiliation: Apellis Pharmaceuticals, Inc.

• Name: Clinical trial
• Affiliation: Apellis Pharmaceuticals, Inc.

Key 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, N meningitidis (types A, C, W, Y, and B), and H 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)


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 48

Exclusion criteria:
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 Part 2 of study participation, but the dosage may be altered or the drug discontinued at any time by the investigator for any safety concern. Riluzole-naïve 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 Part 2 of study participation, but the dosage may be altered or the drug discontinued at any time by the investigator for any safety concern. Edaravone-naïve 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 6 months 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
20. Subjects with known allergy or hypersensitivity to pegcetacoplan or to any of the components
21. Kn

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Amyotrophic Lateral Sclerosis
MedDRA version: 21.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: Aspaveli
Product Name: Pegcetacoplan
Product Code: APL-2
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: PEGCETACOPLAN
CAS Number: 2019171-69-6
Current Sponsor code: APL-2
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 54-
Pharmaceutical form of the placebo: Solution for injection/infusion
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: The primary objective of this study is to assess the efficacy of twice per week subcutaneous (SC) doses of pegcetacoplan 1080 mg compared to placebo in subjects with sporadic ALS as measured by the Combined Assessment of Function and Survival (CAFS) rank score (joint-rank score)

Primary end point(s): the difference in CAFS rank score (joint-rank score) at Week 52

Secondary Objective: •To assess the effect of pegcetacoplan compared to placebo as measured by the Revised ALSFRS-R score
•To assess the effect of pegcetacoplan compared to placebo on disease progression as measured by respiratory function through percentage of slow vital capacity (%SVC)
•To determine the effect of pegcetacoplan compared to placebo on muscle strength as measured by handheld dynamometry (HHD)
•To determine the effect of pegcetacoplan compared to placebo on survival or specified state of disease progression
•To assess the effect of pegcetacoplan compared to placebo on health-related quality of life as measured by ALSAQ-40
•To assess the safety of pegcetacoplan during the randomized and open-label treatment periods through incidence and severity of TEAEs, clinical laboratory tests (hematology, chemistry), vital signs, and physical examinations
•To assess the long-term efficacy of pegcetacoplan using ALSFRS-R, %SVC, HHD, and ALSAQ-40 during the open-label treatment period

Timepoint(s) of evaluation of this end point: Week 52

Secondary Outcome(s)

Secondary end point(s): •Change from baseline in ALSFRS-R at Week 52
•Change from baseline in %SVC (at clinic visits) at Week 52
•Change from first assessment of %SVC (home spirometry) at Week 52
•Change from baseline in HHD megascore at Week 52
•Time to death, permanent tracheostomy, or permanent assisted ventilation up to Week 52
•Time to death up to Week 52
•Change from baseline in ALSAQ-40 at Week 52
•Change from baseline of the randomized treatment period (Visit 2) and of the open-label treatment period (Visit 15) to Week 104 for ALSFRS-R, %SVC, HHD, and ALSAQ-40
•Time to death, permanent tracheostomy, or permanent assisted ventilation up to Week 104
•Time to death up to Week 104

Timepoint(s) of evaluation of this end point: Week 52 and week 104

Secondary ID(s)

APL2-ALS-206

Source(s) of Monetary Support

Apellis Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 06/04/2021
Contact: