GS-7977 With Ribavirin for Hepatitis C (SPARE)

NCT01441180 | Completed Phase 1 Results

• 2 other identifiers: 11025811-I-0258
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- GS-7977 is a new drug that is being developed to treat hepatitis C infection. It works by blocking the hepatitis C virus from dividing in the body. This medication has been used along with other medications commonly used to treat hepatitis C, such as interferon and ribavirin. When used with interferon and ribavirin, GS-7977 seems to be very effective in eliminating the hepatitis C virus from the body. However, interferon can have serious side effects, so researchers want to see if GS-7977 can work by itself or with only ribavirin. Objectives: \- To test the safety and effectiveness of GS-7977 alone or given with ribavirin for hepatitis C infection. Eligibility: \- Individuals at least 18 years of age who have hepatitis C with liver disease, and have never received drugs for it. Design:

• This study will require multiple clinic visits over 18 months. A liver biopsy will be required before the start of the study if participants have not had one within the past 3 years.
• Participants will be screened with a medical history and physical exam.
• Participants will have either GS-7977 alone or GS-7977 with ribavirin. GS-7977 is taken by mouth once a day. Ribavirin is taken by mouth in the morning and evening.
• Participants will have study visits on Days 1, 3, 5, 7, 10, and 14. These visits will involve regular blood tests and symptom monitoring.
• After the second week, participants will have study visits during Weeks 3, 4, 6, 8, 12, 16, and 20. Blood and urine tests will be given to study virus levels in the body, and symptoms will be discussed.
• Participants will stop receiving the study drugs at Week 24.
• Followup clinic visits with blood tests will take place in Weeks 28, 36, 48, 52, 60, and 72. Another liver biopsy will be performed at 48 weeks.
• Some participants may also be part of a smaller study. This study involves frequent blood draws to study drug and virus levels in the blood. The study will require a 36-hour hospital inpatient visit.

Conditions

Hepatitis C

Keywords

Direct Acting Antiviral; Liver; Hepatitis C; HCV

Outcome Measures

Primary Outcomes (2)

• Participants With Adverse Events

  Number of participants with Grade 3-4 Adverse Events During the Study Treatment Period as a measure of safety and tolerability.

  24 weeks

• Sustained Virologic Response

  Sustained virology response at 24 weeks post treatment completion

  24 weeks post treatment completion

Study Arms (3)

Phase 1

EXPERIMENTAL

Participants (N =10) will receive GS-7977 QD in combination with RBV for a total of 24 weeks. The study team will perform an interim evaluation of data and safety at the end of 12 weeks of treatment.

Drug: GS7977; Drug: RBV

Phase 2 Arm A

ACTIVE COMPARATOR

(N =25) 24 weeks of GS-7977 QD in combination with weight based RBV (1000 mg for participants weighing \<75 kg and 1200 mg for participants weighing ≥75kg)

Drug: GS7977; Drug: RBV

Phase 2 Arm B

ACTIVE COMPARATOR

(N = 25): 24 weeks of GS-7977 QD with low dose RBV (600mg).

Drug: GS7977; Drug: RBV

Interventions

GS7977 DRUG

drug intervention

Also known as: sofosbuvir

Phase 1; Phase 2 Arm A; Phase 2 Arm B

RBV DRUG

drug intervention

Also known as: ribasphere, ribapak

Phase 1; Phase 2 Arm A; Phase 2 Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Over 18 years of age at screening
• A female is allowed to enter and participate in the study if she is either of:
• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any female who:
• Has had a hysterectomy or
• Has had a bilateral oophorectomy (ovariectomy) or
• Is post-menopausal (a demonstration of a total cessation of menses for greater than or equal to 1 year)
• Has had a bilateral tubal ligation or fallopian tube inserts
• Childbearing potential, has a negative serum pregnancy test at Screening, and agrees to acceptable birth control such as any of the following:
• Complete abstinence from sexual intercourse from 2 weeks prior to administration of the study drug until completion of the follow-up procedures and at least 6 months after the last dose of RBV
• Vasectomized partner
• Use of an intrauterine device from 2 weeks prior to administration of study drug until completion of the Follow-up procedures and at least 6 months after the last dose of RBV\< TAB\>
• Double contraceptive method (condom or occlusive cap \[diaphragm or cervical/vault caps\]; spermicidal foam/gel/film/cream/suppository; oral, implantable, transdermal, or injectable contraceptives)
• This is advised on the basis of using RBV, which may have a potential teratogenic effect on the fetus in pregnant women. Furthermore reproductive and developmental toxicity studies have not been conducted with GS-7977.
• A male is allowed to enter and participate in the study if he either:
• Is sterile or

You may not qualify if:

• No more than 20 percent of the subjects randomized into the study will be cirrhotic.
• Positive test at Screening for HBsAg, anti-HBc IgM Ab, or anti-HIV Ab.
• History of any other clinically significant chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, Wilson s disease, greater than or equal to 1-antitrypsin deficiency, alcoholic liver disease, \> Grade 1 Stage 1 non-alcoholic steatohepatitis and toxin exposures).
• Treatment with unlicensed herbal/natural remedies suggested to be taken for hepatitis treatment such as Milk thistle or Cats Claw within 28 days of Day 0.
• Participants with a history of ascites, variceal hemorrhage, hepatic encephalopathy, or conditions consistent with decompensated liver disease.
• Screening or baseline ECG with clinically significant ECG findings.
• A personal history of or first degree relative with a history of Torsade de pointes.
• Any substance detected during the screening process that, in the opinion of the investigator, is thought to affect protocol compliance or drug metabolism and disposition.
• Abnormal hematological and biochemical parameters, including:
• Neutrophil count \< 1000 cells/mm(3)
• Hemoglobin \< 11 g/dL in women and \< 12 g/dL in men
• Platelet count less than or equal to 75,000 cells/mm(3)
• Estimated GFR, calculated by the CKD-EPI equation, \< 50 mL/min/ per 1.73 m(2)
• ALT or AST greater than or equal to 10 times ULN
• Serum lipase greater than or equal to 1.5 times ULN (at Screening or during the Screening period)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (6)

• Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006 May 16;144(10):705-14. doi: 10.7326/0003-4819-144-10-200605160-00004.

  PMID: 16702586 BACKGROUND

• Kim WR. The burden of hepatitis C in the United States. Hepatology. 2002 Nov;36(5 Suppl 1):S30-4. doi: 10.1053/jhep.2002.36791.

  PMID: 12407574 BACKGROUND

• Kim WR, Brown RS Jr, Terrault NA, El-Serag H. Burden of liver disease in the United States: summary of a workshop. Hepatology. 2002 Jul;36(1):227-42. doi: 10.1053/jhep.2002.34734. No abstract available.

  PMID: 12085369 BACKGROUND

• Sidharthan S, Kohli A, Sims Z, Nelson A, Osinusi A, Masur H, Kottilil S. Utility of hepatitis C viral load monitoring on direct-acting antiviral therapy. Clin Infect Dis. 2015 Jun 15;60(12):1743-51. doi: 10.1093/cid/civ170. Epub 2015 Mar 2.

  PMID: 25733369 DERIVED

• Meissner EG, Wu D, Osinusi A, Bon D, Virtaneva K, Sturdevant D, Porcella S, Wang H, Herrmann E, McHutchison J, Suffredini AF, Polis M, Hewitt S, Prokunina-Olsson L, Masur H, Fauci AS, Kottilil S. Endogenous intrahepatic IFNs and association with IFN-free HCV treatment outcome. J Clin Invest. 2014 Aug;124(8):3352-63. doi: 10.1172/JCI75938. Epub 2014 Jul 1.

  PMID: 24983321 DERIVED

• Osinusi A, Meissner EG, Lee YJ, Bon D, Heytens L, Nelson A, Sneller M, Kohli A, Barrett L, Proschan M, Herrmann E, Shivakumar B, Gu W, Kwan R, Teferi G, Talwani R, Silk R, Kotb C, Wroblewski S, Fishbein D, Dewar R, Highbarger H, Zhang X, Kleiner D, Wood BJ, Chavez J, Symonds WT, Subramanian M, McHutchison J, Polis MA, Fauci AS, Masur H, Kottilil S. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA. 2013 Aug 28;310(8):804-11. doi: 10.1001/jama.2013.109309.

  PMID: 23982366 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hepatitis C

Interventions

Sofosbuvir; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Ribonucleosides; Nucleosides

Results Point of Contact

• Title: Dr. Shyam Kottilil
• Organization: NIAID/NIH

skottilil@niaid.nih.gov

301-435-0936

Study Officials

• Shyamasundaran Kottilil, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2011
• First Posted: September 27, 2011
• Study Start: September 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: July 1, 2014
• Last Updated: September 26, 2014
• Results First Posted: September 26, 2014

Record last verified: 2014-09

Locations

US (1)