An Extension Study to Evaluate the Long-term Safety and Efficacy of Pegcetacoplan (APL-2) in Subjects with Geographic Atrophy Secondary to AMD

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Apellis Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

30 Nov 2021 → 5 Sep 2025

Decision date (initial)

2024-09-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-512945-18-00

EudraCT number

2020-002931-32

ClinicalTrials.gov

NCT04770545

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

To evaluate the long-term safety of IVT-injected pegcetacoplan

Secondary objectives 4

1. 1. To assess changes in the total area of geographic atrophy (GA) lesion in the study eye measured by fundus autofluorescence (FAF).
2. 2. To assess changes in visual function as measured by: a. Normal-luminance best-corrected visual acuity score (NL-BCVA) in the study eye b. Low-luminance best-corrected visual acuity score (LL-BCVA) in the study eye c. Reading speed in the study eye
3. 3. To assess the macular functional response as assessed by mesopic microperimetry in the study eye (selected participants [those who had the assessment performed in the antecedent study] only).
4. 4. To evaluate changes in participant-reported outcomes as measured by: a. National Eye Institute Visual Functioning Questionnaire 25 Item Version (NEI VFQ-25) b. Functional Reading Independence (FRI) Index.

Conditions and MedDRA coding

Geographic Atrophy Secondary to Age-Related Macular Degeneration

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Ocular-specific inclusion criteria apply to the study eye. 1. Participated in APL2-103 (NCT03777332) or completed the treatment at month 24 of either APL2-303 (Derby, NCT03525613) or APL2-304 (Oaks, NCT03525600). Specifically, for the APL2-303 and APL2-304 studies, the following criterion also applies: a. Participants who did not permanently discontinue treatment but missed the month 24 visit are also eligible to participate in this extension study; however, to be eligible, these participants must be screened within 60 days from the last day of the expected month 24 visit window for the antecedent study.
2. 2. Clarity of ocular media, adequate pupillary dilation, and fixation to permit the collection of good quality images as determined by the investigator. Inclusion criterion #2 applies to the fellow eye.
3. 3. Female participants must be: a. Women of nonchildbearing potential, or b. Women of childbearing potential (WOCBP), defined as any women who have experienced menarche and who are not permanently sterile or postmenopausal, must have a negative serum pregnancy test at screening and must agree to use protocol defined methods of contraception for the duration of the study and 90 days after their last dose of pegcetacoplan, and refrain from breastfeeding for the duration of the study.
4. 4. Males with female partners of childbearing potential must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study and for 90 days after their last dose of pegcetacoplan.
5. 5. Willing and able to give informed consent and to comply with the study procedures and assessments.

Exclusion criteria 6

1. Ocular-specific exclusion criteria apply to the study eye. 1. Participants who permanently discontinued the study drug prior to month 24 in the APL2-304 or APL2-304 studies and only for safety assessments. Temporary pause of the study drug is not exclusionary.
2. 2. Presence of an active ocular disease that, in the opinion of the investigator, compromises or confounds visual function, including, but not limited to, macular hole or other macular diseases (eg, clinically significant epiretinal membrane). Benign conditions in the opinion of the investigator such as peripheral retinal dystrophy are not exclusionary. Exclusion criteria 2 and 3 apply to the fellow eye.
3. 3. Any contraindication to IVT injection including current ocular or periocular infection. Exclusion criteria 2 and 3 apply to the fellow eye.
4. 4. Medical or psychiatric condition that, in the opinion of the investigator, is clinically significant and not suitable for study participation or make consistent follow-up over the 36-month treatment period unlikely.
5. 5. Known hypersensitivity to fluorescein sodium for injection or hypersensitivity to pegcetacoplan or any of the excipients in pegcetacoplan solution.
6. 6. Pregnancy, breastfeeding, or positive pregnancy test.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence and severity of ocular and systemic Aes

Secondary endpoints 11

1. 1.The total area of GA lesion(s) in the study eye (in mm2) as assessed by fundus autofluorescence (FAF)
2. 2.The rate of GA lesion growth in the study eye as assessed by fundus autofluorescence (FAF)
3. 3.NL-BCVA score (study eye) as assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) chart
4. 4. LL-BCVA score (study eye) as assessed by ETDRS chart
5. 5. Monocular maximum reading speed (study eye) corrected for number of words read incorrectly as assessed by Minnesota Reading (MNRead) charts or Radner charts
6. 6. Binocular maximum reading speed, corrected for number of words read incorrectly, as assessed by MNRead charts or Radner charts
7. 7.The number of absolute scotomatous points (study eye) assessed by mesopic microperimetry (selected participants [those who had the assessment performed in the antecedent study] only)
8. 8. Macular sensitivity (study eye) as assessed by mesopic microperimetry (selected participants [those who had the assessment performed in the antecedent study] only)
9. 9. Change in additional microperimetry parameters in the study eye (eg, 95% bivariate contour ellipse area [BCEA], number of points with a clinically significant decrease in mean sensitivity)
10. 10.Mean FRI Index score
11. 11. NEI VFQ25 and NEI VFQ-39 (at select sites) composite score, near activity subscale score, distance activity subscale score, and NEI VFQ-25 driving subscale score

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Apellis Pharmaceuticals Inc.

Sponsor organisation

Apellis Pharmaceuticals Inc.

Address

100 5th Avenue

City

Waltham

Postcode

02451-8703

Country

United States

Scientific contact point

Organisation

Apellis Pharmaceuticals Inc.

Contact name

Clin. Development and Med. Affairs

Public contact point

Organisation

Apellis Pharmaceuticals Inc.

Contact name

Clin. Development and Med. Affairs

Third parties 6

Locations

7 EU/EEA countries · 41 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 31 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications