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

NCT02352493 | Completed Phase 1 Results

• 1 other identifier: ALN-CC5-001
• Study Type: interventional
• Target: 62
• Locations: 2 countries
• Sites: 4

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

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Keywords

PNH; RNAi therapeutic

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events

  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)

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

Secondary Outcomes (9)

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

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

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

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

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

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

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

  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

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

  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

Study Arms (2)

ALN-CC5

ACTIVE COMPARATOR

Drug: ALN-CC5

Sterile Normal Saline (0.9% NaCl)

PLACEBO COMPARATOR

Drug: Sterile Normal Saline (0.9% NaCl)

Interventions

ALN-CC5 DRUG

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

ALN-CC5

Sterile Normal Saline (0.9% NaCl) DRUG

calculated volume to match active comparator

Sterile Normal Saline (0.9% NaCl)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adequate complete blood counts, liver and renal function
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Alnylam Pharmaceuticals: lead

Study Sites (4)

Clinical Trial Site

Barcelona, Spain

Location

Clinical Trial Site

Leeds, United Kingdom

Location

Covance Clinical Research Unit

Leeds, United Kingdom

Location

Richmond Pharmacology

London, United Kingdom

Location

Related Publications (2)

• Ishigooka H, Katsumata H, Saiga K, Tokita D, Motoi S, Matsui C, Suzuki Y, Tomimatsu A, Nakatani T, Kuboi Y, Yamakawa T, Ikeda T, Ishii R, Imai T, Takagi T, Tanabe K. Novel Complement C5 Small-interfering RNA Lipid Nanoparticle Prolongs Graft Survival in a Hypersensitized Rat Kidney Transplant Model. Transplantation. 2022 Dec 1;106(12):2338-2347. doi: 10.1097/TP.0000000000004207. Epub 2022 Nov 22.

  PMID: 35749284 DERIVED

• Badri P, Jiang X, Borodovsky A, Najafian N, Kim J, Clausen VA, Goel V, Habtemariam B, Robbie GJ. Pharmacokinetic and Pharmacodynamic Properties of Cemdisiran, an RNAi Therapeutic Targeting Complement Component 5, in Healthy Subjects and Patients with Paroxysmal Nocturnal Hemoglobinuria. Clin Pharmacokinet. 2021 Mar;60(3):365-378. doi: 10.1007/s40262-020-00940-9.

  PMID: 33047216 DERIVED

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Alnylam Pharmaceuticals, Inc.

Clinicaltrials@alnylam.com

866.330.0326

Study Officials

• Nader Najafian, MD

  Alnylam Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2015
• First Posted: February 2, 2015
• Study Start: January 1, 2015
• Primary Completion: April 1, 2016
• Study Completion: August 1, 2017
• Last Updated: March 30, 2020
• Results First Posted: March 30, 2020

Record last verified: 2020-03

Locations

GB (3); ES (1)