Clinical Trial: Study to Assess Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of RO7112689 in Healthy Volunteers and Participants With Paroxysmal Nocturnal Hemoglobinuria

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: An Adaptive Phase I/II Study to Assess Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of RO7112689 in Healthy Volunteers and Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Brief Summary: This is a Phase I/II, first-in-human study consisting of 3 sequential parts in which the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single-doses of RO7112689 will be evaluated in healthy volunteers (HV) during Part I, and safety, tolerability, PK, PD, and efficacy of multiple-doses of RO7112689 will be evaluated in participants with paroxysmal nocturnal hemoglobinuria (PNH) during Parts 2 and 3 of the study.

Detailed Summary:
Sponsor: Hoffmann-La Roche

Current Primary Outcome:

  • Part 1: Percentage of Participants With Dose-Limiting Events (DLEs) [ Time Frame: Baseline up to approximately 3 months ]
  • Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to approximately 3 months ]
  • Parts 2, 3: Percentage of Participants With AEs and SAEs [ Time Frame: Baseline up to approximately 8 months ]
  • Part 2: Percentage of Participants With Terminal Complement Activity, as Assessed by Ex Vivo Liposome Lysis in Serum Using the Liposome Immunoassay (LIA) [ Time Frame: Baseline up to Day 224 ]
  • Part 3: Percentage of Participants With Terminal Complement Activity, as Assessed by Ex Vivo Liposome Lysis in Serum Using the LIA [ Time Frame: Baseline up to Day 224 ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Part 1: Percentage of Participants With Terminal Complement Activity, as Assessed by Ex Vivo Liposome Lysis in Serum Using the LIA [ Time Frame: Part 1: Baseline up to Day 91 (assessed at predose [Hr 0], EOI [1 Hr], Hr 2, 6, 12 on Day 1; Days 2, 3, 4, 5, 7, 14, 21, 28, 35, 42, 56, 84, 91) ]
  • Part 2: Serum Lactate Dehydrogenase (LDH) Levels [ Time Frame: Predose (Hr0), Hr 10-12 on Days 1, 8; Days 2, 5, 9, 15, 22, 29, 36, 43, 50, 64, 78, 92, 106, 120, 134, 224 ]
  • Part 3: Serum LDH Levels [ Time Frame: Part 3: Predose (Hr 0), Hr 10-12 on Day 1; predose (Hr 0), on Days 2, 8, 15, 22, 29, 36, 57, 71, 85, 99, 113, 127, 134; Day 224 ]
  • Part 1: Total Complement Component 5 (C5) Concentration [ Time Frame: Part 1: Predose (Hr 0), EOI (1 Hr), Hr 2, 6, 12 on Day 1; Days 2, 3, 4, 5, 7, 14, 21, 28, 35, 42, 56, 84, 91 ]
  • Part 2: Total C5 Concentration [ Time Frame: Part 2: Predose (Hr 0), EOI (1 Hr), Hr 2, 6, 10-12 on Day 1; Days 2, 5, 9, 15, 29, 224; predose [Hr 0], EOI [1 Hr], Hr 10-12 on Days 8, 22; predose [Hr 0] on Day 36, 43, 50, 64, 78, 92, 106, 120, 134 ]
  • Part 3: Total C5 Concentration [ Time Frame: Part 3: Predose (Hr 0), EOI (1 Hr), Hr 2, 6 on Day 1; predose (Hr 0), on Days 2, 8, 15, 22, 29, 36, 43, 57, 71, 85, 99, 113, 134; Day 224 ]
  • Part 1: Target C5 Concentration [ Time Frame: Part 1: Predose (Hr 0), EOI (1 hr), Hr2, 6, 12 on Day 1; Days 2, 3, 4, 5, 7, 14, 21, 28, 35, 42, 56, 84, 91 ]
  • Part 2: Target C5 Concentration [ Time Frame: Part 2: Predose (Hr 0), EOI (1 Hr), Hr 2, 6,10-12 on Day 1; Days 2, 5, 9, 15, 29, 224; predose [Hr 0], EOI [1 Hr], Hr 10-12 on Days 8, 22; predose [Hr 0] on Day 36, 43, 50, 64, 78, 92, 106, 120, 134 ]
  • Part 3: Target C5 Concentration [ Time Frame: Part 3: Predose (Hr 0), EOI (1 hr), Hr 2, 6 on Day 1; predose (Hr 0), on Days 2, 8, 15, 22, 29, 36, 43, 57, 71, 85, 99, 113, 134; Day 224 ]
  • Part 2: Change From Baseline in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score at Day 8, 22, 36, 50 and 64 [ Time Frame: Baseline, Day 8, 22, 36, 50, 64 ]
  • Part 3: Change From Baseline in Fatigue as Measured by FACIT-Fatigue Scale Score at Day 2, 8, 15, 29, 57 [ Time Frame: Baseline, Day 2, 8, 15, 29, 57 ]
  • Part 2: Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Score at Day 8, 22, 36, 50, and 64 [ Time Frame: Baseline, Day 8, 22, 36, 50, 64 ]
  • Part 3: Change From Baseline in HRQoL as Measured by EORTC QLQ-C30 Score at Day 2, 8, 15, 29, 57 [ Time Frame: Baseline, Day 2, 8, 15, 29, 57 ]
  • Part 2: Participant Treatment Satisfaction as Measured by Treatment Satisfaction With Medication Questionnaire (TSQM) Score at Day 8, 22, 36, 50 and 64 [ Time Frame: Baseline, Day 8, 22, 36, 50, 64 ]
  • Part 3: Participant Treatment Satisfaction as Measured by TSQM Score at Day 2, 8, 15, 29, 57 [ Time Frame: Baseline, Day 2, 8, 15, 29, 57 ]
  • Part 2: Number of Packed Red Blood Cell (RBC) Units Transfused per Participant [ Time Frame: Baseline up to Day 224 ]
  • Part 3: Number of Packed RBCs Units Transfused per Participant [ Time Frame: Baseline up to Day 224 ]
  • Part 2: Percentage of Participants With Packed RBC Units Transfused [ Time Frame: Baseline up to Day 224 ]
  • Part 3: Percentage of Participants With Packed RBC Units Transfused [ Time Frame: Baseline up to Day 224 ]
  • Part 1: Percentage of Participants With Anti-Drug Antibodies (ADAs) to RO7112689 [ Time Frame: Part 1: Day 1 up to Day 91 (assessed at predose [Hour 0] on Day 1; on Days 14, 28, 56, 84, and 91) ]
  • Part 2: Percentage of Participants With ADAs to RO7112689 [ Time Frame: Part 2: Day 1 up to Day 224 (assessed at predose [Hour 0] on Days 1, 8; on Days 29, 50, 106, 134, and 224) ]
  • Part 3: Percentage of Participants With ADAs to RO7112689 [ Time Frame: Part 3: Day 1 up to Day 224 (assessed at predose [Hour 0] on Days 1, 8, 29, 57, 99, 134; on Day 224) ]


Original Secondary Outcome: Same as current

Information By: Hoffmann-La Roche

Dates:
Date Received: November 1, 2016
Date Started: November 14, 2016
Date Completion: February 17, 2018
Last Updated: May 16, 2017
Last Verified: May 2017