Study to Assess Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Healthy Volunteers and Participants With Paroxysmal Nocturnal Hemoglobinuria

Conditions

• Paroxysmal Hemoglobinuria, Nocturnal

Eligibility Criteria

Sex

ALL

Age

18 Years - 75 Years

Healthy Volunteers

Accepted

Interventions

• Crovalimab — DRUG
  Crovalimab will be administered as per schedule described in individual arm.
• Placebo — DRUG
  Placebo will be administered as per schedule described in Part 1 placebo arm.

Study Details

This is a Phase I/II, first-in-human study consisting of four sequential parts and an open-label extension (OLE). The safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single doses of crovalimab will be evaluated in healthy volunteers (HV) during part 1. The safety, tolerability, PK and PD of multiple doses of crovalimab will be evaluated in participants with paroxysmal nocturnal hemoglobinuria (PNH) in parts 2, 3, 4, and OLE of the study. Efficacy of crovalimab will be evaluated in Parts 2, 3, and 4.

Key Dates

Start date

Nov 14, 2016

Status verified

May 2026

Primary completion

Sep 30, 2026

Completion

Sep 30, 2026

Study Design

Enrollment

59 participants (actual)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Part 1 (Healthy Volunteers): Crovalimab
  Healthy participants will receive a single dose of crovalimab in each dose-escalation cohort of Part 1. Crovalimab will be administered at a starting dose of 75 milligrams (mg) intravenous (IV) infusion. Doses are planned to be escalated up to Cohort 5.
• Placebo Comparator: Part 1 (Healthy Volunteers): Placebo
  Healthy participants will receive a single dose of crovalimab matching placebo in each dose-escalation cohort of Part 1.
• Experimental: Part 2 (PNH Participants): Crovalimab
  PNH participants will receive 3 single ascending doses (375 mg IV, 500 mg IV, 1000 mg IV of crovalimab) on Days 1, 8, and 22 followed by weekly crovalimab administrations up to a maximum of 5 months. Weekly crovalimab administrations will start no earlier than Day 36. The starting dose of Part 2 is based on data from Part 1 of the study.
• Experimental: Part 3 (PNH Participants): Crovalimab QW
  Participants will receive crovalimab at a dose of 1000 mg on Day 1 and 170 mg weekly (QW) starting on Day 8 for a maximum treatment duration of 5 months.
• Experimental: Part 3 (PNH Participants): Crovalimab Q2W
  Participants will receive crovalimab at a dose of 1000 mg on Day 1 and 340 mg every 2 weeks (Q2W) for a maximum treatment duration of 5 months.
• Experimental: Part 3 (PNH Participants): Crovalimab Q4W
  Participants will receive crovalimab at a dose of 1000 mg on Day 1 and 680 mg every 4 weeks (Q4W) starting on Day 8 for a maximum treatment duration of 5 months.
• Experimental: Part 4 (eculizumab pretreated PNH Participants): Crovalimab
  PNH Participants pretreated with eculizumab will receive crovalimab: Participants \>/= 100 kilograms (kg): loading dose of 1500 mg IV on Day 1; Participants \< 100 kg: loading dose of 1000 mg IV on Day 1. In all Participants, the remainder of the loading series schedule will be 340 mg subcutaneous (SC) on Days 2, 8, 15, and 22. For Participants \>/= 100 kg, maintenance dosing will be 1020 mg SC on week 5 and then Q4W thereafter. Patients \< 100 kg will receive a maintenance dose of 680 mg SC on the same schedule.
• Experimental: Part 4 (treatment naïve PNH Participants): Crovalimab
  Treatment naïve PNH Participants will receive: Participants \>/= 100 kg: loading dose of 1500 mg IV on day 1; Participants \< 100 kg: loading dose of 1000 mg IV on day 1. In all Participants, the remainder of the loading series schedule will be 340 mg SC on Days 2, 8, 15, and 22. For Participants \>/= 100 kg, maintenance dosing will be 1020 mg SC on week 5 and then Q4W thereafter. Patients \< 100 kg will receive a maintenance dose of 680 mg SC on the same schedule.
• Experimental: OLE (PNH Participants): Crovalimab
  PNH Participants who participated in Parts 2, 3 and 4 and who derive clinical benefit from crovalimab may enroll into OLE. Participants will either receive 680 mg SC Q4W (body weight \>/= 40 kg to \< 100 kg) or 1020 mg SC Q4W (body weight \>/= 100 kg) for up to a maximum treatment duration of ten years from entry into OLE.

Primary Outcome Measure

Part 1: Percentage of Participants With Dose-Limiting Events (DLEs) [ Time Frame: Baseline up to approximately 3 months ]