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

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ClinicalTrials.gov Identifier: NCT02352493
Recruitment Status : Completed
First Posted : February 2, 2015
Results First Posted : March 30, 2020
Last Update Posted : March 30, 2020
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

Study Description
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Brief Summary:
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

Condition or disease Intervention/treatment Phase
Paroxysmal Nocturnal Hemoglobinuria (PNH) Drug: ALN-CC5 Drug: Sterile Normal Saline (0.9% NaCl) Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official 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
Study Start Date : January 2015
Actual Primary Completion Date : April 2016
Actual Study Completion Date : August 2017

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Arms and Interventions
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Arm Intervention/treatment
Active Comparator: ALN-CC5 Drug: ALN-CC5
Single or multiple doses of ALN-CC5 by subcutaneous (sc) injection
Placebo Comparator: Sterile Normal Saline (0.9% NaCl) Drug: Sterile Normal Saline (0.9% NaCl)
calculated volume to match active comparator


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02352493


Locations
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Spain
Clinical Trial Site
Barcelona, Spain
United Kingdom
Clinical Trial Site
Leeds, United Kingdom
Covance Clinical Research Unit
Leeds, United Kingdom
Richmond Pharmacology
London, United Kingdom
Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
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Study Director: Nader Najafian, MD Alnylam Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Alnylam Pharmaceuticals:
Statistical Analysis Plan  [PDF] November 18, 2016
Study Protocol: Clinical Study Protocol  [PDF] June 12, 2017
Study Protocol: Amendment Summary of Changes  [PDF] June 12, 2017

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02352493    
Other Study ID Numbers: ALN-CC5-001
First Posted: February 2, 2015    Key Record Dates
Results First Posted: March 30, 2020
Last Update Posted: March 30, 2020
Last Verified: March 2020
Keywords provided by Alnylam Pharmaceuticals:
PNH
RNAi therapeutic
Additional relevant MeSH terms:
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Hemoglobinuria
Hemoglobinuria, Paroxysmal
Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
 Anemia, Hemolytic
Anemia
Hematologic Diseases
Myelodysplastic Syndromes
Bone Marrow Diseases