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
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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 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 |
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 |
- 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)
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
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Ages Eligible for Study: | 18 Years to 45 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
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
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
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 |
Study Director: | Nader Najafian, MD | Alnylam Pharmaceuticals |
Documents provided by Alnylam Pharmaceuticals:
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 |
PNH RNAi therapeutic |
Hemoglobinuria Hemoglobinuria, Paroxysmal Proteinuria Urination Disorders Urologic Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases |
Male Urogenital Diseases Urological Manifestations Anemia, Hemolytic Anemia Hematologic Diseases Myelodysplastic Syndromes Bone Marrow Diseases |