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Completed

NCT Number: NCT02352493

A Phase 1/2 Study of an Investigational Drug, ALN-CC5, in Healthy Adult Volunteers and Patients With PNH

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ALN-CC5 in healthy adult volunteers and subjects with PNH

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Key information

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH) Anemia Anemia, Hemolytic Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinuria, Paroxysmal Myelodysplastic Syndromes

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Clinical Trial Site, Barcelona, Spain

Loading trial locations.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adequate complete blood counts, liver and renal function
  • 12-lead electrocardiogram (ECG) within normal limits
  • Female subjects of child bearing potential agreeing to use a protocol specified method of contraception
  • Male subjects agreeing to use protocol specified methods of contraception
  • Willing to provide written informed consent and willing to comply with study requirements

Exclusion criteria

  • Any uncontrolled or serious disease, or any medical or surgical condition, that may interfere with participation in the clinical study and/or put the subject at significant risk
  • Received an investigational agent within 90 days before the first dose of study drug or are in follow-up of another clinical study
  • History of multiple drug allergies or intolerance to subcutaneous injection
  • Parts A and B of the study: Used prescription medications within 14 days or 7 half-lives of administration of the first dose of study drug.
  • History of meningococcal infection

Treatment and study plan

ALN-CC5

Drug

Single or multiple doses of ALN-CC5 by subcutaneous (sc) injection

Sterile Normal Saline (0.9% NaCl)

Drug

calculated volume to match active comparator

Primary outcomes

  1. Number of Participants With Adverse Events

    Time frame: Part A: through day 658; Part B: through day 532; Part C: through day 280

    Adverse events were reported for single-ascending doses (SAD) or multiple ascending doses (MAD) of ALN-CC5 when administered to healthy adult subjects and of multiple doses (MD) in patients with paroxysmal nocturnal hemoglobinuria (PNH)

Secondary outcomes

  1. Pharmacodynamic (PD) Effect of ALN-CC5: Percentage Reduction From Baseline in Complement Alternative Pathway (CAP)

    Time frame: Part A: through day 70; Part B: through day 140; Part C: through day 140

    Complement activity was measured in serum samples collected at timepoints throughout the study using the CAP ELISA assay. Percentage reduction was calculated relative to baseline levels. A positive value indicates a reduction in CAP from baseline.

  2. Pharmacodynamic (PD) Effect of ALN-CC5: Percentage Reduction From Baseline in Complement Classical Pathway (CCP)

    Time frame: Part A: through day 70; Part B: through day 140; Part C: through day 140

    Complement activity was measured in serum samples collected at time points throughout the study using the CCP ELISA assay. Percentage reduction was calculated relative to baseline levels. A positive value indicates a reduction in CCP from baseline.

  3. Pharmacodynamic (PD) Effect of ALN-CC5: Percentage Reduction From Baseline in C5 Protein Levels

    Time frame: Part A: through day 70; Part B: through day 140; Part C: through day 140

    Total C5 protein levels were measured in serum samples collected at time points throughout the study using a mass spectrometry-based method. Percentage reduction was calculated relative to baseline levels. A positive value indicates a reduction in C5 protein level from baseline.

  4. Pharmacokinetic (PK) Effect of ALN-CC5: Cmax (25-mer)

    Time frame: Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84

    Maximum observed plasma concentration (Cmax) of ALN-CC5 (cemdisiran) 25-mer.

  5. Pharmacokinetic (PK) Effect of ALN-CC5: Cmax (23-mer)

    Time frame: Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84

    Maximum observed plasma concentration (Cmax) of ALN-CC5 (cemdisiran) 23-mer.

  6. Pharmacokinetic (PK) Effect of ALN-CC5: T Max (25-mer)

    Time frame: Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84

    Time of maximum observed plasma concentration (T max) of ALN-CC5 (cemdisiran) 25-mer.

  7. Pharmacokinetic (PK) Effect of ALN-CC5: T Max (23-mer)

    Time frame: Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84

    Time of maximum observed plasma concentration (T max) of ALN-CC5 (cemdisiran) 23-mer.

  8. Pharmacokinetic (PK) Effect of ALN-CC5: AUC 0-t (25-mer)

    Time frame: Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84

    Area under the plasma concentration-time curve over the dosing interval zero to time (AUC 0-t) of ALN-CC5 (cemdisiran) 25-mer.

  9. Pharmacokinetic (PK) Effect of ALN-CC5: AUC 0-t (23-mer)

    Time frame: Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84

    Area under the plasma concentration-time curve over the dosing interval zero to time (AUC 0-t) of ALN-CC5 (cemdisiran) 23-mer.

Sponsors and collaborators

Lead sponsor

Alnylam Pharmaceuticals

Industry

Registry information

Official study title

A Phase 1/2 Single-ascending and Multiple-ascending Dose, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Subcutaneously Administered ALN-CC5 in Healthy Adult Volunteers and Patients With Paroxysmal Nocturnal Hemoglobinuria

Important dates

Study start
2015
Primary completion
2016
Study completion
2017
First posted
Feb 2, 2015
Registry last updated
Mar 30, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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