Clinical trial NCT02605993: Open-label, Multiple Ascending Dose Study of Ravulizumab (ALXN1210) in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Official title: A Phase 2, Open-label, Multiple Ascending Dose Study to Evaluate the Efficacy, Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of ALXN1210 Administered Intravenously to Patients With Paroxysmal Nocturnal Hemoglobinuria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Paroxysmal Nocturnal Hemoglobinuria
PNH
Keywords: complement inhibitor
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2015-11-17
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to evaluate the safety, tolerability, and efficacy of multiple intravenous (IV) doses of ravulizumab administered to complement inhibitor treatment-naïve participants with PNH.

Detailed description: The study consisted of a screening period of up to 30 days and a Treatment Period of up to 253 days for Cohorts 1-3 and 281 days for Cohort 4. After completion of the Treatment Period, all participants had the opportunity to enter the Extension Period, wherein participants continue to receive ravulizumab for up to 5 years. The first dose in the Extension Period occurred on Day 253 for Cohorts 1-3 and on Day 281 for Cohort 4.

The data presented includes the Primary Completion date of the study for the Treatment Period. The results for the Extension Period will be reported after study completion.

Eligibility criteria: Inclusion Criteria:

1. Male or female ≥18 years of age
2. PNH diagnosis confirmed by documented high-sensitivity flow cytometry
3. Documented meningococcal vaccination not more than 3 years prior to dosing
4. Female participants of childbearing potential were to use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.
5. Willing and able to give written informed consent and comply with the study visit schedule

Exclusion Criteria:

1. Treatment with a complement inhibitor at any time
2. Female participants who are planning to become pregnant, or are pregnant, breastfeeding or who had a positive pregnancy test at screening or Day 1
3. Participation in an interventional clinical study within 30 days before initiation of dosing on Day 1, or use of any experimental therapy within 30 days prior to dosing on Day 1, or within 5 half-lives of the investigational product, whichever was greater
4. History of allergy to any drug, allergen, excipients of ravulizumab or known allergy to Chinese hamster ovary cell proteins
5. Inability to comply with study requirements
6. History of any clinically significant cardiac, hepatic, immunologic, pulmonary, or rheumatoid disease that, in the Investigator's judgment, would preclude participation
7. Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the participant unsuitable for enrollment

Primary outcomes:
measure: Percent Change In LDH Levels From Baseline To Day 253 And Day 281
timeFrame: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
Secondary outcomes:
measure: Percent Change In Free Hemoglobin Levels From Baseline To Day 253 And Day 281
timeFrame: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
measure: Percent Change In Haptoglobin Levels From Baseline To Day 253 And Day 281
timeFrame: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
measure: Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 253 And Day 281
timeFrame: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
measure: Percent Change In PNH RBC Types II And III Clone Size From Baseline To Day 253
timeFrame: Baseline, Day 253 (Cohorts 1 to 4)
measure: Percent Change In D-dimer From Baseline To Day 253 And Day 281
timeFrame: Baseline to Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
measure: Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
timeFrame: Baseline, Day 253 (Cohorts 1 to 3) and Day 281 (Cohort 4)
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Clinical Trial Site
state: Ontario
city: Lyon
country: France
facility: Clinical Trial Site
state: Pierre-Bénite
city: Lille
country: France
facility: Clinical Trial Site
city: Paris
country: France
facility: Clinical Trial Site
city: Ulm
country: Germany
facility: Clinical Trial Site
state: Baden Wuerttemberg
city: Aachen
country: Germany
facility: Clinical Trial Site
state: Nordrhein Westfalen
city: Essen
country: Germany
facility: Clinical Trial Site
state: Nordrhein Westfalen
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Badalona
country: Spain
facility: Clinical Trial Site
state: Barcelona
city: Majadahonda
country: Spain
facility: Clinical Trial Site
state: Madrid
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Madrid
country: Spain
facility: Clinical Trial Site
city: Taipei City
country: Taiwan
facility: Clinical Trial Site
city: Leeds
country: United Kingdom
facility: Clinical Trial Site
state: West Yorkshire
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
References:
citation: Roth A, Rottinghaus ST, Hill A, Bachman ES, Kim JS, Schrezenmeier H, Terriou L, Urbano-Ispizua A, Wells RA, Jang JH, Kulasekararaj AG, Szer J, Aguzzi R, Damokosh AI, Shafner L, Lee JW. Ravulizumab (ALXN1210) in patients with paroxysmal nocturnal hemoglobinuria: results of 2 phase 1b/2 studies. Blood Adv. 2018 Sep 11;2(17):2176-2185. doi: 10.1182/bloodadvances.2018020644.